beta-carotene and Lung-Neoplasms

β-Carotene, which is derived from most fruits and vegetables, is the most common type of carotenes. Existing studies have demonstrated that β-carotene is associated with some positive health outcomes. However, results about the effects of supplemental β-carotene on cancer are inconsistent.. To determine the association between supplemental β-carotene intake and the risk of cancers.. Eight databases (PubMed, Web of Science, Embase, Cochrane, China National Knowledge Infrastructure, Wangfang, China Science and Technology Journal Database, and Chinese Biomedical Literature Database) were systematically searched until September 2022.. Only reports from randomized controlled trials in which an association between supplemental β-carotene intake and the risk of cancer was found were included in the meta-analysis.. A total of 18 eligible studies based on 8 different randomized controlled trials were included in the meta-analysis, with varying sample sizes from 391 to 39 876 participants. There was no significant association between supplemental β-carotene intake and overall cancer incidence rate after synthesizing all the results (risk ratio [RR]: 1.02; 95% confidence interval [CI], 0.99-1.05). Results from subgroup analysis indicated that intake of supplemental β-carotene significantly increased the risk of lung cancer (RR: 1.19; 95%CI: 1.08-1.32), whereas no significant associations were observed for other site-specific cancers. In addition, smokers and the subgroup of participants with only low-dose β-carotene intake had a risk increment of cancer if they took supplemental β-carotene (RR: 1.16; 95%CI: 1.05-1.29).. β-Carotene supplementation has no beneficial or harmful effect on cancer incidence; moreover, it might have potentially harmful effects on lung cancer, especially for people who smoke. On the basis of the evidence from this study, supplemental intake of β-carotene is not recommended for preventing cancer, and the establishment of a tolerable upper intake level of β-carotene should be considered.

Topics: Antioxidants; beta Carotene; Dietary Supplements; Humans; Lung Neoplasms; Randomized Controlled Trials as Topic

Lung cancer is one of the most common neoplasms globally, with about 2.2 million new cases and 1.8 million deaths annually. Although the most important factor in reducing lung cancer risk is lifestyle change, most patients favour the use of supplements, for example, rather than quitting smoking or following a healthy diet. To better understand the efficacy of such interventions, a systematic review was performed of data from randomized controlled trials concerning the influence of beta-carotene supplementation on lung cancer risk in subjects with no lung cancer before the intervention. The search corpus comprised a number of databases and eight studies involving 167,141 participants, published by November 2021. The findings indicate that beta-carotene supplementation was associated with an increased risk of lung cancer (RR = 1.16, 95% CI = 1.06-1.26). This effect was even more noticeable among smokers and asbestos workers (RR = 1.21, 95% CI = 1.08-1.35) and non-medics (RR = 1.18, 95% CI = 1.07-1.29). A meta-regression found no relationship between the beta-carotene supplementation dose and the size of the negative effect associated with lung cancer risk. Our findings indicate that beta-carotene supplementation has no effect on lung cancer risk. Moreover, when used as the primary chemoprevention, beta-carotene may, in fact, increase the risk of lung cancer.

Topics: Antioxidants; beta Carotene; Dietary Supplements; Humans; Lung Neoplasms; Smoking

Cardiovascular disease and cancer are the 2 leading causes of death in the US, and vitamin and mineral supplementation has been proposed to help prevent these conditions.. To review the benefits and harms of vitamin and mineral supplementation in healthy adults to prevent cardiovascular disease and cancer to inform the US Preventive Services Task Force.. MEDLINE, PubMed (publisher-supplied records only), Cochrane Library, and Embase (January 2013 to February 1, 2022); prior reviews.. English-language randomized clinical trials (RCTs) of vitamin or mineral use among adults without cardiovascular disease or cancer and with no known vitamin or mineral deficiencies; observational cohort studies examining serious harms.. Single extraction, verified by a second reviewer. Quantitative pooling methods appropriate for rare events were used for most analyses.. Mortality, cardiovascular disease events, cancer incidence, serious harms.. Eighty-four studies (N=739 803) were included. In pooled analyses, multivitamin use was significantly associated with a lower incidence of any cancer (odds ratio [OR], 0.93 [95% CI, 0.87-0.99]; 4 RCTs [n=48 859]; absolute risk difference [ARD] range among adequately powered trials, -0.2% to -1.2%) and lung cancer (OR, 0.75 [95% CI, 0.58-0.95]; 2 RCTs [n=36 052]; ARD, 0.2%). However, the evidence for multivitamins had important limitations. Beta carotene (with or without vitamin A) was significantly associated with an increased risk of lung cancer (OR, 1.20 [95% CI, 1.01-1.42]; 4 RCTs [n=94 830]; ARD range, -0.1% to 0.6%) and cardiovascular mortality (OR, 1.10 [95% CI, 1.02-1.19]; 5 RCTs [n=94 506] ARD range, -0.8% to 0.8%). Vitamin D use was not significantly associated with all-cause mortality (OR, 0.96 [95% CI, 0.91-1.02]; 27 RCTs [n=117 082]), cardiovascular disease (eg, composite cardiovascular disease event outcome: OR, 1.00 [95% CI, 0.95-1.05]; 7 RCTs [n=74 925]), or cancer outcomes (eg, any cancer incidence: OR, 0.98 [95% CI, 0.92-1.03]; 19 RCTs [n=86 899]). Vitamin E was not significantly associated with all-cause mortality (OR, 1.02 [95% CI, 0.97-1.07]; 9 RCTs [n=107 772]), cardiovascular disease events (OR, 0.96 [95% CI, 0.90-1.04]; 4 RCTs [n=62 136]), or cancer incidence (OR, 1.02 [95% CI, 0.98-1.08]; 5 RCTs [n=76 777]). Evidence for benefit of other supplements was equivocal, minimal, or absent. Limited evidence suggested some supplements may be associated with higher risk of serious harms (hip fracture [vitamin A], hemorrhagic stroke [vitamin E], and kidney stones [vitamin C, calcium]).. Vitamin and mineral supplementation was associated with little or no benefit in preventing cancer, cardiovascular disease, and death, with the exception of a small benefit for cancer incidence with multivitamin use. Beta carotene was associated with an increased risk of lung cancer and other harmful outcomes in persons at high risk of lung cancer.

Topics: Adult; Advisory Committees; beta Carotene; Cardiovascular Diseases; Dietary Supplements; Humans; Lung Neoplasms; Minerals; Neoplasms; Primary Prevention; United States; Vitamin A; Vitamins

Previous observational studies have suggested that the effect of diet-derived circulating micronutrient concentrations on lung cancer (LC) risk is controversial. We conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between circulating micronutrient concentrations and the overall risk of LC and three LC subtypes (namely lung adenocarcinoma (LA), squamous cell lung cancer (SqCLC), and small cell lung cancer (SCLC)). The instrumental variables (IVs) of 11 micronutrients (beta-carotene, calcium, copper, folate, lycopene, magnesium, phosphorus, retinol, selenium, zinc, and vitamin B6) were screened from the published genome-wide association studies (GWAS). Summary statistics related to LC and its subtypes came from the largest meta-analysis, including 29,266 cases and 56,450 controls. Inverse-variance weighted (IVW) method is used as the main MR analysis, and the sensitivity analysis is carried out to ensure the MR assumptions. This MR study found suggestive evidence that genetically predicted 6 circulating micronutrient concentrations was correlated with the risk of overall LC (odds ratio (OR): 1.394, 95% confidence interval (CI): 1.041-1.868,

Topics: beta Carotene; Calcium; Carcinoma, Non-Small-Cell Lung; Copper; Genome-Wide Association Study; Humans; Lung Neoplasms; Mendelian Randomization Analysis; Micronutrients; Phosphorus; Polymorphism, Single Nucleotide; Vitamin A; Zinc

This is the second update of this Cochrane Review. Some studies have suggested a protective effect of antioxidant nutrients and higher dietary levels of fruits and vegetables on lung cancer.. To determine whether vitamins and minerals and other potential agents, alone or in combination, reduce lung cancer incidence and lung cancer mortality in healthy populations.. We searched CENTRAL, MEDLINE and Embase from 1974 to May 2019 and screened references included in published studies and reviews.. We included randomised controlled trials (RCTs) comparing vitamins or mineral supplements with placebo, administered to healthy people with the aim of preventing lung cancer.. Four review authors independently selected the trials to be included in the review, assessed their methodological quality and extracted data. For dichotomous outcomes we calculated risk ratios (RRs) and 95% confidence intervals (CIs) and pooled results using the random-effects model. We assessed the risk of bias using Cochrane's 'Risk of bias' assessment tool and certainty of evidence using the GRADE approach.. In this update, we identified three new trials for a total of 12 studies. Six analysed vitamin A, three vitamin C, three combined vitamin D3 + calcium, four vitamin E combined with other products, one selenium supplements and nine studied combinations of two or more products. Four studies included only men and five only women. Vitamin A results in little to no difference in lung cancer incidence (RR 1.09, 95% CI 1.00 to 1.19; 5 RCTs, 212314 participants; high-certainty evidence) and lung cancer mortality (RR 1.06, 95% CI 0.81 to 1.38; 3 RCTs, 190118 participants; high-certainty evidence). But in smokers or asbestos workers vitamin A increases the risk of lung cancer incidence (RR 1.10, 95% CI 1.01 to 1.20; 3 RCTs, 43995 participants; high-certainty evidence), lung cancer mortality (RR 1.18, 95% CI 1.01 to 1.38; 2 RCTs, 29426 participants; high-certainty evidence) and all-cause mortality (RR 1.09, 95% CI 1.05 to 1.13; 2 RCTs, 32883 participants; high-certainty evidence). Vitamin A increases the risk of minor side effects, such as yellowing of the skin and minor gastrointestinal symptoms (high-certainty evidence). Vitamin C likely results in little to no difference in lung cancer incidence (RR 1.29, 95% CI 0.67 to 2.49; 2 RCTs, 14953 participants; moderate-certainty evidence). In women, vitamin C increases the risk of lung cancer incidence (RR 1.84, 95% CI 1.14 to 2.95; 1 RCT, 7627 participants; high-certainty evidence). In men, vitamin C results in little to no difference in mortality for lung cancer (RR 0.81, 95% CI 0.53 to 1.23; 1 RCT, 7326 participants; high-certainty evidence). Vitamin D + calcium may result in little to no difference in lung cancer incidence in postmenopausal women (RR 0.90, 95% CI 0.39 to 2.08; 3 RCTs, 37601 women; low-certainty evidence). Vitamin E results in little to no difference in lung cancer incidence (RR 1.01, 95% CI 0.90 to 1.14; 3 RCTs, 36841 participants; high-certainty evidence) or to lung cancer mortality (RR 0.96, 95% CI 0.77 to 1.18; 2 RCTs, 29214 participants; high-certainty evidence), but increases the risk of haemorrhagic strokes (hazard ratio (HR), 1.74, 95% CI 1.04 to 2.91; 1 RCT, 14641 participants; high-certainty evidence). Calcium results in little to no difference in lung cancer incidence in postmenopausal women (RR 0.65, 95% CI 0.13 to 3.18; 1 RCT, 733 participants) or in risk of renal calculi (RR 1.94, 95% CI 0.20 to 18.57; 1 RCT, 733 participants; low-certainty evidence). Selenium in men results in little t. Well-designed RCTs have shown no beneficial effect of supplements for the prevention of lung cancer and lung cancer mortality in healthy people. Vitamin A supplements increase lung cancer incidence and mortality in smokers or persons exposed to asbestos. Vitamin C increases lung cancer incidence in women. Vitamin E increases the risk of haemorrhagic strokes.

Topics: alpha-Tocopherol; Ascorbic Acid; beta Carotene; Calcium, Dietary; Cholecalciferol; Confidence Intervals; Dietary Supplements; Female; Health Status; Humans; Incidence; Lung Neoplasms; Male; Minerals; Randomized Controlled Trials as Topic; Selenium; Selenium Compounds; Sex Factors; Vitamin A; Vitamin E; Vitamins

Whether dietary β-carotene and vitamin A intake protect against lung cancer risk is not clear. Therefore, we performed this meta-analysis to investigate the association between them. The related articles were searched using the databases PubMed and the Web of Knowledge up to May 2015. We used the random-effect model to estimate the relative risk (RR) and their 95% CI. Small-study effect was assessed using Egger's test. In total, 19 studies comprising 10,261 lung cancer cases met the inclusion criteria. The pooled RR and their 95% CI was 0.855 (0.739-0.989) for higher category of dietary vitamin A intake and lung cancer risk, especially among Asian populations and in the cohort studies. Evidence from 18 studies suggested that higher category of dietary β-carotene intake could reduce lung cancer risk (0.768 (0.675-0.874)).The associations were also significant in American and Asian populations. In conclusions, higher category of dietary β-carotene and vitamin A intakes could reduce the risk of lung cancer. However, the dose-response analysis was not performed due to the limited data in each individual study. Due to this limitation, further studies with detailed dose, cases and person-years for β-carotene and vitamin A of each category are wanted to assess this dose-response association.

Topics: Animals; beta Carotene; Databases, Factual; Diet; Disease Models, Animal; Humans; Lung Neoplasms; Risk Factors; Sensitivity and Specificity; Vitamin A

This is an updated version of the original review published in Issue 2, 2003. Some studies have suggested a protective effect of antioxidant nutrients on lung cancer. Observational epidemiological studies suggest an association between higher dietary levels of fruits and vegetables containing beta-carotene and a lower risk of lung cancer.. To determine whether vitamins, minerals and other potential agents, alone or in combination, reduce incidence and mortality from lung cancer in healthy people.. For this update we have used a search strategy adapted from the design in the original review. The following electronic databases have been searched up to December 2011: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). References included in published studies and reviews were also screened.. Included studies were randomised controlled clinical trials comparing different vitamins, mineral supplements or supplements with placebo, administered to healthy people with the aim of preventing lung cancer.. Two authors independently selected the trials to be included in the review, assessed the methodological quality of each trial and extracted data using a standardised form. For each study, relative risk and 95% confidence limits were calculated for dichotomous outcomes and pooled results were calculated using the random-effect model.. In the first version of this review four studies were included; in this review update, an additional five studies have been included. Four studies included only males and two only females; two studies included only participants considered at high risk, namely smokers or exposed to asbestos, and one study included people deficient in many micronutrients. Six studies analysed vitamin A, three vitamin C, four vitamin E, one selenium supplements, and six studied combinations of two or more products. All the RCTs included in this review were classified as being of low risk of bias.For people not at high risk of lung cancer and compared to placebo, none of the supplements of vitamins or minerals or their combinations resulted in a statistically significant difference in lung cancer incidence or mortality, except for a single study that included 7627 women and found a higher risk of lung cancer incidence for those taking vitamin C but not for total cancer incidence, but that effect was not seen in males or when the results for males and females were pooled.For people at high risk of lung cancer, such as smokers and those exposed to asbestos and compared to placebo, beta-carotene intake showed a small but statistically significant higher risk of lung cancer incidence, lung cancer mortality and for all-causes mortality.. There is no evidence for recommending supplements of vitamins A, C, E, selenium, either alone or in different combinations, for the prevention of lung cancer and lung cancer mortality in healthy people. There is some evidence that the use of beta-carotene supplements could be associated with a small increase in lung cancer incidence and mortality in smokers or persons exposed to asbestos.

Topics: alpha-Tocopherol; Ascorbic Acid; beta Carotene; Dietary Supplements; Female; Health Status; Humans; Lung Neoplasms; Male; Minerals; Randomized Controlled Trials as Topic; Selenium Compounds; Vitamin A; Vitamins

Clinical trials of β-carotene supplementation and recent large-scale prospective studies have called into question the protective effects of vegetable and fruit consumption against lung cancer. To re-assess this issue, we reviewed data from Japanese epidemiological studies.. Original data were obtained from searches of MEDLINE and the Japana Centra Revuo Medicina (Ichushi) database. The associations were assessed based on their magnitude and the strength of the evidence, together with their biological plausibility as previously evaluated by the International Agency for Research on Cancer.. We identified six cohort studies and four case-control studies on the consumption of vegetables and/or fruit. We focused on fruit and green-yellow vegetables as food items, as they were included in more of the studies, and insufficient data were available on other types of vegetables. Among the three cohort and two case-control studies that reported on green-yellow vegetables, only one of each study type showed a weak inverse association between lung cancer risk and their consumption. Two of the four cohort studies and one (or possibly two) of the four case-control studies demonstrated a weak inverse correlation between lung cancer risk and fruit consumption. Meta-analysis for fruit consumption revealed a summary relative risk that was significantly smaller than unity.. Our analysis of the Japanese epidemiological data showed that fruit consumption possibly decreased the risk of lung cancer, but found insufficient evidence of a link with vegetable consumption. Further prospective studies should assess the effects of consuming these food groups.

Topics: Anticarcinogenic Agents; Asian People; beta Carotene; Case-Control Studies; Cohort Studies; Feeding Behavior; Fruit; Humans; Japan; Lung Neoplasms; Risk Assessment; Vegetables

Despite reported antiproliferative activity of vitamin A and its common use for cancer, there is no comprehensive synthesis of its safety and efficacy in lung cancers. To address this issue we conducted a systematic review of the safety and efficacy of vitamin A for the treatment and prevention of lung cancers.. Two independent reviewers searched six electronic databases from inception to July 2009 for clinical, observational, and preclinical evidence pertaining to the safety and efficacy of vitamin A and related retinoids for lung cancers. 248 studies were included for full review and analysis. Five RCTs assessed treatment of lung cancers, three assessed primary prevention, and three looked at secondary prevention of lung cancers. Five surrogate studies, 26 phase I/II, 32 observational, and 67 preclinical studies were also included. 107 studies were included for interactions between vitamin A and chemo- or radiation-therapy. Although some studies demonstrated benefits, there was insufficient evidence overall to support the use of vitamin A or related retinoids for the treatment or prevention of lung cancers. Retinyl palmitate combined with beta carotene increased risk of lung cancer in smokers in the large CARET trial. Pooling of three studies pertaining to treatment and three studies on secondary prevention revealed no significant effects on response rate, second primary tumor, recurrence, 5-year survival, and mortality. There was a small improvement in event free survival associated with vitamin A compared to controls, RR 1.24 (95% CI 1.13-1.35). The synthetic rexinoid bexarotene increased survival significantly among a subset of patients in two RCTs (p<0.014, <0.087).. There is a lack of evidence to support the use of naturally occurring retinoids for the treatment and prevention of lung cancers. The rexinoid bexarotene may hold promise for use among a subset of patients, and deserves further study.

Topics: Animals; beta Carotene; Diterpenes; Humans; Lung Neoplasms; Retinoids; Retinyl Esters; Vitamin A

In view of safety concerns surrounding the use of pharmaceuticals such as nonsteroidal anti-inflammatory drugs and tamoxifen as cancer chemopreventive agents, potentially innocuous phytochemicals derived from the diet are considered attractive alternatives. However, results from cancer chemoprevention trials of dietary agents have been disappointing to date, as promising activities observed in rodent models and cells in vitro have not translated into clinical success. This may be partly due to the development process for these agents, which is complex for a number of reasons; the definitive end point, inhibition of carcinogenesis, requires large numbers of individuals followed-up over many years. Furthermore, whereas biomarkers are frequently used as surrogate efficacy end points to expedite the process, biomarker assessment and validation has proven difficult because dietary agents exert multiple actions with an unknown hierarchy of biological importance. These factors have made determining the dose for clinical investigation extremely challenging, and at present, there are no defined strategies for rationally identifying the most appropriate doses. In this commentary, the complexities involved in the development of dietary chemoprevention agents are discussed, and a tentative route towards selection of the optimal clinical dose is proposed. The approach highlights the need to conduct long-term preclinical studies with realistic concentrations that are achievable in human tissues and the importance of efficacy biomarkers that are intrinsically linked to the key mechanisms of action. A more logical design of studies should increase the likelihood that the encouraging preclinical results observed for many phytochemicals translate into tangible clinical benefit.

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Biomarkers; Cell Line, Tumor; Clinical Trials as Topic; Colorectal Neoplasms; Diet; DNA Adducts; Dose-Response Relationship, Drug; Drug Discovery; Drug Screening Assays, Antitumor; Female; Folic Acid; Genistein; Humans; Lung Neoplasms; Male; Plant Extracts; Plants, Edible; Rats

Lung cancer is the most common type of cancer, excluding nonmelanoma skin cancer, and is the leading cause of cancer death in the United States. Notable carcinogens involved in the development of lung cancer include smoking, secondhand smoke, and radon. Lung cancer is divided into 2 major types: non-small-cell lung cancer, the most prevalent, and small-cell lung cancer. Treatment includes surgery, chemotherapy, radiation, or a combination of the same. Medical nutrition therapy is often required for nutrition-related side effects of cancer treatment, which include but are not limited to anorexia, nausea and vomiting, and esophagitis. The best protection against lung cancer is avoidance of airborne carcinogens and increased consumption of fruits and vegetables. Studies have shown that smokers taking large amounts of beta-carotene and vitamin A supplements had increased lung cancer incidence and mortality. However, ingestion of beta-carotene from foods, along with a diet rich in fruits and vegetables, has a protective role against lung disease. The use of complementary and alternative medicine by lung cancer patients is prevalent; therefore, clinicians should investigate whether complementary and alternative therapies are used by patients and advise them on the use of these therapies to avoid any potential side effects and interactions with conventional therapies. The article concludes with a case study of a patient with non-small-cell lung cancer and illustrates the use of medical nutrition therapy in relation to cancer treatment side effects.

Topics: Aged; Anorexia; Antineoplastic Agents, Phytogenic; beta Carotene; Complementary Therapies; Diet; Dietary Supplements; Dysgeusia; Female; Gastrointestinal Diseases; Humans; Lung Neoplasms; Smoking; Vitamin A; Vomiting

A number of epidemiological studies have reported associations of beta-carotene plasma levels or intake with decreased lung cancer risk. However, intervention studies in smokers have unexpectedly reported increased lung tumor rates after high, long-term, beta-carotene supplementation. Recently, detailed analyses by stratification for smoking habits of several large, long-term intervention or epidemiological trials are now available. The ATBC study, the CARET study, the Antioxidant Polyp Prevention trial, and the E3N study provide evidence that the adverse effects of beta-carotene supplementation are correlated with the smoking status of the study participants. In contrast, the Physician Health Study, the Linxian trial, and a pooled analysis of 7 epidemiological cohort studies have not supported this evidence. The ferret and A/J mouse lung cancer model have been used to investigate the mechanism of interaction of beta-carotene with carcinogens in the lung. Both models have specific advantages and disadvantages. There are a number of hypotheses concerning the beta-carotene/tobacco smoke interaction including alterations of retinoid metabolism and signaling pathways and interaction with CYP enzymes and pro-oxidation/DNA oxidation. The animal models consistently demonstrate negative effects only in the ferret, and following dosing with beta-carotene in corn oil at pharmacological dosages. No effects or even protective effects against smoke or carcinogen exposure were observed when beta-carotene was applied at physiological dosages or in combination with vitamins C and E, either as a mixture or in a stable formulation. In conclusion, human and animal studies have shown that specific circumstances, among them heavy smoking, seem to influence the effect of high beta-carotene intakes. In normal, healthy, nonsmoking populations, there is evidence of beneficial effects.

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Dietary Supplements; Ferrets; Humans; Lung; Lung Neoplasms; Mice; Risk; Smoking; Species Specificity

Some studies have suggested that beta-carotene supplementation may increase the risk of lung cancer, particularly among smokers or former smokers. Beta-carotene, a provitamin A, is available in multivitamins. In the current study, the authors investigated the risk of lung cancer associated with beta-carotene in smokers or former smokers and surveyed the beta-carotene content in national brand multivitamins.. The authors systemically reviewed the published literature using a search of the MEDLINE database and performed a meta-analysis of large randomized trials that reported on the effect of beta-carotene supplementation on the incidence of lung cancer among smokers or former smokers. A sample of multivitamins was evaluated for their beta-carotene content and the suggested daily dosage.. Four studies contributing 109,394 subjects were available for analysis. The average daily beta-carotene dosage in these trials ranged from 20 to 30 mg daily. Among current smokers, beta-carotene supplementation was found to be significantly associated with an increased risk of lung cancer (odds ratio [OR], 1.24; 95% confidence interval [95% CI], 1.10-1.39). Among former smokers, there was no significant increase noted (OR, 1.10; 95% CI, 0.84-1.45). In a sample of 47 common multivitamins, beta-carotene was present in 70% of the identified formulas. The median dosage of beta-carotene was 0.3 mg (range, 0-17.2 mg) daily. The beta-carotene content was found to be significantly higher among multivitamins sold to improve visual health than among other multivitamins, with a median daily dosage of 3 mg (range, 0-24 mg).. High-dose beta-carotene supplementation appears to increase the risk of lung cancer among current smokers. Although beta-carotene was prevalent in multivitamins, high-dose beta-carotene was observed among multivitamin formulas sold to promote visual health.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Dietary Supplements; Female; Humans; Lung Neoplasms; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Assessment; Smoking; Smoking Cessation

The objective of this paper was to review the strategies for lung cancer chemoprevention. A retrospective assessment of the major findings from the most informative lung cancer chemoprevention clinical trials [alpha-tocopherol (vitamin E), beta-carotene trial and beta-carotene and retinol efficacy trial] was employed. Both trials and many others showed no benefit from what was once the prime candidate for lung cancer chemoprevention, beta-carotene. Furthermore, both trials found that beta-carotene, alone or in combination with vitamin E or retinyl palmitate, increased the incidence of lung cancers and the total and cardiovascular mortality rates. In conclusion, design, conduct, documentation, relationships with participants, and preparedness for unexpected findings are all important for chemoprevention research. Trials are necessary to test inferences from observational epidemiology and animal models. Multiple classes of promising agents are available for evaluation and for eventual randomized trials.

Topics: Anticarcinogenic Agents; beta Carotene; Chemoprevention; Clinical Trials as Topic; Humans; Lung Neoplasms; Vitamin A

Nutritional theories have been greatly strengthened by the results of the AREDS study, showing efficiency of high doses of beta-carotene, vitamin C and E, and Zinc to prevent severe forms of age-related macular degeneration (AMD). Despite an excellent tolerance of these high doses, some concerns have been expressed about potential side-effects of non nutritional doses. For example, high doses of beta carotene should not be given to smokers because they could activate the occurrence of a lung cancer. Many ophthalmologists replace beta carotene by lutein and zeaxanthin, while efficiency of this association has not been proven. The AREDS study raises many questions but stimulates the research into the prevention of AMD. Future studies should include polyunsaturated fatty acids and lutein and zeaxanthin supplementations as they seem to be among the most promising preventive therapies in AMD.

Topics: Aged; beta Carotene; Causality; Comorbidity; Dietary Supplements; Humans; Lung Neoplasms; Lutein; Macular Degeneration; Middle Aged; Risk Assessment; Smoking; Vitamins; Xanthophylls; Zeaxanthins

Beta-carotene is a natural food component that is present in fruits and vegetables and is also used as a food colorant and a supplement. Beta-carotene is an anti-oxidant and a source of vitamin A. It is endowed with health beneficial properties, but a number of studies showed that with high intakes it may increase the risk for lung cancer in at risk individuals (heavy smokers, asbestos workers and alcohol users). To establish the window of benefit, it is necessary to identify early markers of effect and to obtain insight in the mechanism of action of beta-carotene, in the absence and presence of environmental risk factors. Genomics technologies are well suited to dissect the mechanisms of action and identify the markers of effect. Human cell lines can be used to analyse the effects of beta-carotene, but exposure studies with beta-carotene show that cell lines display a widely variant behaviour, which hampers translation to the in vivo situation in humans. Alternatively, animal studies can be used. Especially the ferret seems to be a good model, but little sequence information of this species is available. However, heterologous hybridization on human cDNA seems possible and provides and a new tool for molecular analysis of health effects of beta-carotene.

Topics: Animals; Antioxidants; beta Carotene; Cell Line; Clinical Trials as Topic; Dietary Supplements; Dietetics; Humans; Lung Neoplasms; Models, Animal; No-Observed-Adverse-Effect Level; Oligonucleotide Array Sequence Analysis; Risk Assessment

Dr. James Allen Olson helped us to define the role of beta-carotene in human health by categorizing these as "functions, actions and associations." In the last decade, significant research has shown that beta-carotene acts as an antioxidant in biologically relevant systems, affects several aspects of human immune function and higher intake/serum levels are associated with improvements in certain physiological functions such as lung function. The unexpected findings of increased lung cancer in beta-carotene supplemented smokers in the ATBC and CARET intervention studies have resulted in the need for expanded research efforts to define the mechanism(s) of action of beta-carotene. Recent survey data as well as laboratory animal studies continue to find an inverse association between beta-carotene and cancer risk. Because beta-carotene is the major source of vitamin A for the majority of the world's population, it is critical to define the safe levels of intake from foods and supplements.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; beta Carotene; Carcinogens; Dietary Supplements; Female; Humans; Immunity; Lung; Lung Neoplasms; Male; Middle Aged; Smoking

Beta-carotene and other carotenoids have been thought to have anti-cancer activity, either because of antioxidant activity or because of their ability to be converted to vitamin A. Nevertheless, two large scale intervention studies in humans using high doses of beta-carotene found that beta-carotene supplementation resulted in more lung cancer rather than less lung cancer among smoking and asbestos exposed populations. Studies conducted in the ferret have elucidated molecular mechanisms behind this observation, in that high-dose beta-carotene and smoke exposure in these animals leads to squamous metaplasia, a pre-cancerous lesion in the lung. High dose beta-carotene in the smoke exposed animals was found to give rise to a number of transient oxidative metabolites, which include P450 enzymes that result in the destruction of retinoic acid, and diminished retinoid signaling, and enhanced cell proliferation. In addition, eccentric cleavage beta-carotene metabolites facilitate the binding of smoke derived carcinogens to DNA. In other ferret studies low dose beta-carotene smoke exposure provided mild protection against squamous metaplasia. Thus, it appears that the explanation of the apparent paradoxical effects of beta-carotene on lung cancer is related to dose. The metabolism and breakdown of natural products should be thoroughly investigated in animal models before embarking on large scale intervention trials, particularly when using unusually high doses that greatly exceed normal dietary levels.

Topics: Animals; Asbestos; beta Carotene; Cytochrome P-450 Enzyme System; Dietary Supplements; Dose-Response Relationship, Drug; Ferrets; Humans; Lung; Lung Neoplasms; Neoplasms; Smoking; Tretinoin

Topics: Arteriosclerosis; beta Carotene; Biomarkers; Blood Chemical Analysis; Cardiovascular Diseases; Cataract; Humans; Hyperthyroidism; Liver Diseases; Lung Neoplasms; Pancreatic Diseases; Smoking; Specimen Handling; Stress, Physiological

Since a high concentration of beta-carotene in blood reduces the risk of lung cancer, a large-scale intervention examination containing beta-carotene was conducted, mainly by the National Cancer Institute. The results showed that the risk of lung cancer increased with administration of beta-carotene. This result demonstrates that continuation of smoking is an important factor in the increased risk, and not smoking is confirmed to be the most important prevention method. The authors examined the treatment effect of raising the concentration of folic acid and vitamin B12 in blood on bronchial dysplasia as a pre-cancerous lesion. A significant medical treatment effect was see in the folic acid and vitamin B12 medication groups, which seems promising for the chemoprevention of lung cancer.

Topics: beta Carotene; Bronchi; Drug Administration Schedule; Drug Therapy, Combination; Folic Acid; Humans; Lung Neoplasms; Metaplasia; Smoking Cessation; Vitamin B 12

Some studies have suggested a protective effect of antioxidant nutrients on lung cancer. Observational epidemiological studies suggest an association between higher dietary levels of fruits and vegetables containing beta carotene and a lower risk of lung cancer.. To determine whether vitamins, minerals and other potential agents, alone or in combination, reduce incidence and mortality from lung cancer in healthy people.. The electronic databases MEDLINE (1966-july 2001), EMBASE (1974-july 2001) and the Cochrane Controlled Trial Register (CENTRAL, Issue 3/2001) and bibliographies were searched. In addition authors of included studies were contacted to identify potentially eligible published and unpublished trials.. Included studies were randomised controlled clinical trials comparing different supplements or comparing supplements with placebo, administered to healthy people with the aim of preventing lung cancer.. Three reviewers independently selected the trials to be included in the review and assessed the methodological quality of each trial, and two extracted data using a standardised form. For each study, relative risk and 95% confidence limits were calculated for dichotomous outcomes.. Four studies were eligible for inclusion. All were population based trials, including a total of 109,394 participants. Two studies included smokers, one included workers exposed to asbestos and two studies were carried out in health professionals. A group of participants with no known risk factors for lung cancer was included in the study sample of two trials. Beta-carotene was evaluated in all trials, alone or combination with alpha-tocopherol or retinol, and one study tested alpha-tocopherol alone. Duration of treatment varied from 2 to 12 years and follow-up was from two to five years. All trials had a placebo group. For people with risk factors for lung cancer no reduction in lung cancer incidence or mortality was found in those taking vitamins alone compared with placebo (incidence of lung cancer: RR 0.98, 95% CI 0.81-1.19; lung cancer mortality: RR 0.93, 95% CI 0.73-1.19). For people with no known risk factors of lung cancer, none of the vitamins or their combinations appeared to have any effect. Combined data from three studies showed a non-statistically significant increased risk of lung cancer incidence (RR 1.11, 95% CI 0.94-1.33) and mortality (RR 1.05, 95% CI 0.87-1.28) for beta-carotene alone at pharmacological doses in groups with risk factors for lung cancer. When beta-carotene was combined with retinol, data from a single study showed that there was a statistically significant, increased risk of lung cancer incidence (RR 1.42, 95% CI 1.13-1.80) and mortality (RR 1.75, 95% CI 1.29-2.38) in people with risk factors for lung cancer who took both vitamins compared with those who took placebo. Data from also from one study showed that the combination of beta-carotene with alpha-tocopherol in people with risk factors for lung cancer was associated with a non-statistically significant increased risk of lung cancer incidence (RR 1.16, 95% CI 0.96-1.39) and mortality (RR 1.15, 95% CI 0.91-1.45). No effect was observed for total cancer incidence, mortality or all-cause mortality.. There is currently no evidence to support recommending vitamins such as alpha-tocopherol, beta-carotene or retinol, alone or in combination, to prevent lung cancer. A harmful effect was found for beta-carotene with retinol at pharmacological doses in people with risk factors for lung cancer (smoking and/or occupational exposure to asbestos). More research from larger trials and with longer follow-up is needed to analyse the effectiveness of other supplements.

Topics: alpha-Tocopherol; beta Carotene; Dietary Supplements; Health Status; Humans; Lung Neoplasms; Minerals; Randomized Controlled Trials as Topic; Vitamin A; Vitamins

Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews and large well-designed original articles were preferred to form the basis of the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and in persons who have never smoked. Vitamin A, C and E supplements and beta-carotene offer no protection against the development of lung cancer. On the contrary, in two major randomised intervention trials beta-carotene supplement has resulted in increased mortality. Smoking remains by far the leading cause of lung cancer and the adverse effects can only be slightly alleviated by a healthy diet.

Topics: beta Carotene; Diet; Feeding Behavior; Humans; Lung Neoplasms; Risk Factors; Smoking; Vitamins

Chemoprevention of cancer is reviewed from the viewpoints of action mechanisms and methodology of clinical trials in order to introduce promising agents discovered by in vitro and/or in vivo studies to applications in humans. The clinical trial procedure essentially follows the phase study which has been employed for chemotherapeutic drugs. Chemoprevention of bladder cancer, prostate cancer, gastric cancer, hepatocellular carcinoma, breast cancer, head and neck cancer, colorectal cancer and lung cancer is reviewed, mainly focusing on clinical trials. Previous clinical trials have shown the effectiveness of the following: polyprenoic acid (acyclic retinoid) for hepatocellular carcinoma; tamoxifen for breast cancer; retinoic acids for head and neck tumor; and aspirin, a COX-2 inhibitor, for colorectal cancer. Despite the advantageous effects of some of these agents, their toxic effects must also be of concern at the same time. For example, in a chemoprevention trial of lung cancer, beta-carotene was unexpectedly found to increase the risk of lung cancer among high-risk groups. It is also noted that large-scale clinical trials demand large research grants, which may not be affordable in Japan. Chemoprevention is still an emerging field of oncology where researchers in both basic and clinical sciences face great challenges.

Topics: Animals; Anticarcinogenic Agents; Antineoplastic Agents; beta Carotene; Breast Neoplasms; Clinical Trials as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Colorectal Neoplasms; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Male; Neoplasms; Prostatic Neoplasms; Tamoxifen; Tretinoin; Urinary Bladder Neoplasms

Topics: alpha-Tocopherol; Antioxidants; beta Carotene; Chronic Disease; Coronary Disease; Dietary Supplements; Humans; Lung Neoplasms; Risk Factors; Selenium

Cancer of the lung causes more deaths from cancer worldwide than at any other site. The environmental, genetic, and dietary risk factors are discussed and progress in chemoprevention is reviewed. A better understanding of the molecular events that occur during carcinogenesis has opened up new areas of research in cancer prevention and a number of biochemical markers of high risk individuals have been identified. It is predicted that greater success in chemoprevention will be achieved in the next decade than in the last.

Topics: beta Carotene; Biomarkers, Tumor; Chemoprevention; Diet; Female; Humans; Lung Neoplasms; Male; Retinoids; Risk Factors

It is logical that the requirement for antioxidant nutrients depends on a person's exposure to endogenous and exogenous reactive oxygen species. Since cigarette smoking results in an increased cumulative exposure to reactive oxygen species from both sources, it would seem cigarette smokers would have an increased requirement for antioxidant nutrients. Logic dictates that a diet high in antioxidant-rich foods such as fruits, vegetables, and spices would be both protective and a prudent preventive strategy for smokers. This review examines available evidence of fruit and vegetable intake, and supplementation of antioxidant compounds by smokers in an attempt to make more appropriate nutritional recommendations to this population.

Topics: Antioxidants; beta Carotene; Biomarkers; Cardiovascular Diseases; Cohort Studies; Dietary Supplements; Feeding Behavior; Food-Drug Interactions; Fruit; Humans; Lung Neoplasms; Oxidative Stress; Randomized Controlled Trials as Topic; Smoking; Vegetables; Vitamin A

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Antioxidants; beta Carotene; Cell Transformation, Neoplastic; Clinical Trials as Topic; Endpoint Determination; Genes, Tumor Suppressor; Humans; Lung Neoplasms; Proto-Oncogenes; Retinoids; Risk Factors

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Cell Transformation, Neoplastic; Diet; Free Radicals; Guinea Pigs; Humans; Incidence; Lung Neoplasms; Melanoma; Mice; Mice, Hairless; Models, Chemical; Neoplasms; Neoplasms, Radiation-Induced; Oxygen; Partial Pressure; Prospective Studies; Reactive Oxygen Species; Retrospective Studies; Selenium; Singlet Oxygen; Skin Neoplasms; Smoking; Structure-Activity Relationship; Ultraviolet Rays; Vegetables; Vitamin E

The growth of our knowledge of carotenoid biochemistry has opened new and divergent paths for research. The earliest role established for beta-carotene in animals was as a vitamin A precursor, a role it shares with several other pro-vitamin A carotenoids. Additional studies have continued to refine our understanding of this function. Because carotenoids are excellent scavengers of singlet oxygen and respectable scavengers for other reactive oxygen species, substantial work was done concerning their potential role as antioxidants. In an unexpected twist, the ability of radicals in cigarette smoke to degrade carotenoids might be responsible for the finding that high-dose dietary beta-carotene increased the incidence of lung cancer in smokers. A new role for the polar carotenoids lutein and zeaxanthin was identified, when those carotenoids were found to constitute the macular pigment (the yellow spot at the center of the human retina). Many different carotenoids can be metabolized to products with retinoid activity, which might affect gene expression and cell differentiation. The formation of retinoids from diverse carotenoids might account for a portion of their activities as anticancer agents. Studies of lycopene in prostate cancer prevention have been very promising, and clinical studies of lycopene are underway. Carotenoids have emerged as the best single tissue marker for a diet rich in fruits and vegetables, and measurements of plasma and tissue carotenoids have an important role in defining the optimal diets for humans.

Topics: Animals; Antioxidants; beta Carotene; Carotenoids; Fruit; Humans; Lung Neoplasms; Macular Degeneration; Neoplasms; Reactive Oxygen Species; Smoking; Vegetables; Vitamin A

Three large-scale clinical trials tested the effects of supplemental beta-carotene on the risk for chronic diseases such as cancer. The populations involved were Finnish male heavy smokers (the Alpha Tocopherol Beta Carotene [ATBC] trial), male asbestos workers and male and female heavy smokers (Beta-Carotene and Retinol Efficacy Trial [CARET]), and U.S. male physicians, 11% of whom were current smokers (Physician's Health Study). All three trials concluded that beta-carotene provided no protection against lung cancer; however, quite unexpectedly, two of the trials found a higher risk for lung cancer for those subjects given beta-carotene compared with those that were not. Several authors concluded from these beta-carotene trials that the protective effects of antioxidants against chronic disease are not as great as had been hoped. As reviewed here, however, beta-carotene may or may not be an antioxidant; it certainly differs in many respects from the prototypical antioxidant, vitamin E. In any case, the majority of beta-carotene's effects in vivo are probably not derived from any antioxidant properties that it may possess, but rather from its effect on a number of biochemical systems. Whether taking supplemental antioxidants can reduce the risk for chronic diseases remains to be established, although the case for vitamin E and heart disease appears strong. However, the association between eating a diet sufficient in fruits and vegetables and reduced risk for a number of diseases is consistent. There is no evidence at present that consuming small amounts of supplemental beta-carotene, i.e., amounts in foods or in a multivitamin tablet, is unwise for any population. The role of supplementation, however, particularly at high levels, with compounds that may be anti-oxidants but that are less well understood than vitamin E (e.g., carotenoids, plant polyphenols, and other phytochemicals), is less clear. The surprising results of the ATBC and CARET trials are a red flag, signaling the need for further research; a number of areas for future work are suggested here. Future research should lead to a clearer understanding of the effects of beta-carotene and other phytochemicals, as well as to more refined strategies for intervention, with important clinical and public health implications.

Topics: beta Carotene; Clinical Trials as Topic; Dietary Supplements; Humans; Lung Neoplasms; Risk Factors

Lung cancer is the major cause of death in industrialized western societies. Its link to tobacco abuse is well established and efforts should be made to eliminate this potent environmental carcinogen. The concept of chemoprevention, the use of agents to inhibit and reverse lung cancer carcinogenesis, has great appeal. The CARET study, conducted in 18,000 high-risk smokers in the US, found that a combination of beta-carotene and retinyl palmitate resulted in a 28% increase in the incidence of lung cancer. A similar study conducted in Finland, the ATBC trial utilizing alpha tocopherol and beta-carotene, had similar findings for the group taking beta-carotene. These two trials have caused a rethinking of the use of natural compounds as chemoprevention agents. These agents should no longer be regarded as harmless, but as having potential toxicities. A new approach in the chemoprevention of cancer has been the concept of surrogate endpoints, biological changes that are on the pathway to cancer. Trials are underway to determine what are appropriate surrogate endpoints for lung cancer chemoprevention trials.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Anticarcinogenic Agents; beta Carotene; Carotenoids; Chromosomes, Human, Pair 3; Clinical Trials as Topic; Cocarcinogenesis; Cytochrome P-450 CYP1A1; Diterpenes; Female; Flavonoids; Genetic Predisposition to Disease; Glutathione Transferase; Humans; Inactivation, Metabolic; Incidence; Lung Neoplasms; Lycopene; Male; Middle Aged; Polymorphism, Genetic; Precancerous Conditions; Retinoids; Retinyl Esters; Risk Factors; Selenium; Smoking; Smoking Prevention; Trace Elements; Treatment Outcome; Vitamin A; Vitamin E

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Cell Division; Dietary Supplements; DNA Damage; Dose-Response Relationship, Drug; Humans; Lung Neoplasms; Oxidation-Reduction; Risk Factors; Smoking; Vitamin E

This paper (and an extensive supplementary report) considers how far cancer/risk factor associations based on epidemiology have been confirmed by evidence from 226 studies involving interventions other than smoking. Many are small, uncontrolled, of unrepresentative populations, concern cancer markers not cancer, and may involve combinations of agents. Many agents suspected of causing cancer are untested by intervention trials. For seven of 16 agents tested (fibre, folic acid, low-fat diet, riboflavin, zinc, vitamin Bs, and vitamin D), the evidence is clearly inadequate to confirm or deny the epidemiology, while the evidence relating to calcium only concerns biomarkers. For other agents, the evidence relating to cancer itself is weak. In studies where cancer is the endpoint, only three effects have been replicated: (a) selenium supplementation and decreased liver cancer incidence, (b) treatment by the retinoid etretinate and reduced bladder tumours in susceptible individuals, and (c) beta-carotene supplementation and increased lung cancer incidence. Studies involving pre-cancerous conditions as the endpoint, which have a number of practical advantages, more frequently report benefits of intervention. Thus, oral pre-cancerous lesions can certainly be reduced by beta-carotene, vitamin A, and other retinoids, and possibly by vitamin E. It also seems that retinoids can reduce pre-cancerous cervix, skin and lung lesions, that vitamin C and the NSAID sulindac can reduce colonic polyps, and that sunscreens can reduce solar keratoses. Our findings clearly show that the great majority of causal relationships suggested by epidemiology have not been validated by intervention trials. This may be partly due to lack of suitable studies of adequate size or duration, or to using single dietary compounds as agents that are by themselves not responsible for the epidemiologically-observed associations between diet and cancer. However, this lack of validation must cause concern in view of the markedly conflicting evidence on beta-carotene and lung cancer between epidemiological and intervention studies. More intervention studies are needed, but in their absence, caution in interpreting epidemiological findings is warranted.

Topics: beta Carotene; Clinical Trials as Topic; Dietary Fiber; Dietary Supplements; Epidemiologic Methods; Etretinate; Humans; Liver Neoplasms; Lung Neoplasms; Neoplasms; Reproducibility of Results; Selenium; Urinary Bladder Neoplasms

Oral cancer is often preceded by precancerous lesions, the most common of which is leukoplakia. Several treatment modalities are available: elimination of the possible cause, cold knife, laser, or cryosurgery, and topical application of bleomycin and 5-fluorouracil. In research, oral leukoplakia is used as a model to study the value of chemoprevention as a strategy to prevent cancer, because its effect is directly visible and material for analysis is easily obtainable from the mouth. In several studies and chemoprevention trials the efficacy of retinoids, retinol and/or beta-carotene on oral leukoplakia has been demonstrated. Second primary tumors occur in 10-30% of head and neck cancer patients and 10% of lung cancer patients. Chemoprevention offers an attractive approach to combat this threat to such patients, which is bound to cast a shadow over their lives. In the last 10-15 years several chemoprevention studies with vitamin A, retinoids or agents working through other mechanisms (antioxidants) have been launched. The largest chemoprevention study in curatively treated early-stage oral cancer, laryngeal cancer and lung cancer (N = 2595) is EUROSCAN, an EORTC study initiated in 1988. End-points are second tumors, local/regional recurrence and distant metastases, and long-term survival rates. Preminary results will be available in 1998.

Topics: beta Carotene; Biomarkers, Tumor; Clinical Trials as Topic; Head and Neck Neoplasms; Humans; Leukoplakia; Lung Neoplasms; Precancerous Conditions; Retinoids; Vitamin A

Isozymes of alcohol and other dehydrogenases convert ethanol and retinol to their corresponding aldehydes in vitro. In addition, new pathways of retinol metabolism have been described in hepatic microsomes that involve, in part, cytochrome P450s, which can also metabolize various drugs. In view of these overlapping metabolic pathways, it is not surprising that multiple interactions between retinol, ethanol, and other drugs occur. Accordingly, prolonged use of alcohol, drugs, or both, results not only in decreased dietary intake of retinoids and carotenoids, but also accelerates the breakdown of retinol through cross-induction of degradative enzymes. There is also competition between ethanol and retinoic acid precursors. Depletion ensues, with associated hepatic and extrahepatic pathology, including carcinogenesis and contribution to fetal defects. Correction of deficiency through vitamin A supplementation has been advocated. It is, however, complicated by the intrinsic hepatotoxicity of retinol, which is potentiated by concomitant alcohol consumption. By contrast, beta-carotene, a precursor of vitamin A, was considered innocuous until recently, when it was found to also interact with ethanol, which interferes with its conversion to retinol. Furthermore, the combination of beta-carotene with ethanol results in hepatotoxicity. Moreover, in smokers who also consume alcohol, beta-carotene supplementation promotes pulmonary cancer and, possibly, cardiovascular complications. Experimentally, beta-carotene toxicity was exacerbated when administered as part of beadlets. Thus ethanol, while promoting a deficiency of vitamin A also enhances its toxicity as well as that of beta-carotene. This narrowing of the therapeutic window for retinol and beta-carotene must be taken into account when formulating treatments aimed at correcting vitamin A deficiency, especially in drinking populations.

Topics: Animals; Antioxidants; beta Carotene; Carcinogens; Central Nervous System Depressants; Drug Synergism; Ethanol; Humans; Liver; Liver Cirrhosis, Alcoholic; Lung Neoplasms; Microsomes, Liver; Vitamin A; Vitamin A Deficiency

The conflicting evidence of the relation between beta-carotene and lung cancer in humans serves as a poignant case study with respect to what types of evidence are sufficient to support or change a nutrition recommendation. This article is a review of the available evidence of the relation between beta-carotene and lung cancer, including data regarding beta-carotene intake (from diet and supplements), beta-carotene biochemical status, and vegetable and fruit consumption, and a discussion of the role of this evidence in making nutrition recommendations. More than 30 case-control and cohort studies were conducted over many years in various populations and indicated that people who eat more vegetables and fruit, foods rich in carotenoids, and carotenoids (beta-carotene in particular), as well as those with higher blood beta-carotene concentrations, have a lower risk of lung cancer than those who eat fewer such foods or have lower beta-carotene concentrations. In contrast, the intervention results from large, controlled trials of beta-carotene supplementation do not support the observed beneficial associations or a role for supplemental beta-carotene in lung cancer prevention; instead, they provide striking evidence for adverse effects (ie, excess lung cancer incidence and overall mortality) in smokers. The findings require that caution be exercised in recommending supplemental beta-carotene, particularly for smokers, and argue against changing the vegetable-fruit recommendations in the direction of greater nutrient specificity. This case study of beta-carotene and lung cancer stresses the importance of having results from at least one, and preferably more, large, randomized intervention trial before public health recommendations concerning micronutrient supplementation are considered.

Topics: Antioxidants; beta Carotene; Diet; Epidemiologic Studies; Fruit; Humans; Lung Neoplasms; Nutrition Policy; Randomized Controlled Trials as Topic; Vegetables

Lung cancer is the most common cancer in the world, and smoking is the major risk factor, accounting for about 90% of the cases. Diet has also been implicated in the development of lung cancer, although the specific nutrients remain to be elucidated. Vitamins with antioxidant activity have received much attention. beta-Carotene, the most efficient provitamin A, was found to be inversely related to the risk of lung cancer in many prospective epidemiological studies, especially in studies measuring serum concentrations of beta-carotene. The findings from controlled trials, however, contradict the hypothesis that beta-carotene could prevent lung cancer, but rather suggest increased risk of lung cancer with supplementary beta-carotene. Data from both prospective studies and a controlled trial suggest no role for vitamin E in lung carcinogenesis. Some prospective epidemiological studies suggest an inverse relationship between dietary vitamin C and the risk of lung cancer, but due to the high correlation between dietary vitamin C and vegetable and fruit intake the independent role of dietary vitamin C is difficult to estimate. Studies using prediagnostic plasma concentrations of ascorbic acid do not support the involvement of vitamin C in lung carcinogenesis, and no controlled trials of vitamin C on lung cancer have been published. Thus, supplementation with antioxidant vitamins cannot be recommended for the prevention of lung cancer. Non-smoking is the most important target in the prevention of lung cancer. High intakes of vegetables and fruits may provide additional protection and are unlikely to be harmful.

Topics: Ascorbic Acid; beta Carotene; Humans; Lung Neoplasms; Risk Factors; Vitamin A; Vitamins

Chemoprevention is defined as the use of specific natural or pharmacologic agents to reverse, suppress, or prevent the carcinogenic process to the development of invasive cancer. The basic idea behind lung cancer chemoprevention is the concept that diffuse injury of the respiratory epithelium results from chronic carcinogen exposure. The rationale for chemoprevention arose from epidemiologic data demonstrating the existence of dietary inhibitors of carcinogenesis, basic studies of epithelial carcinogenesis, and laboratory evidence from animal models. Many of the studies evaluating specific agents focused on vitamin A and its synthetic analogs, the retinoids. Chemoprevention trials have investigated the effect of retinoids and other agents on bronchial metaplasia and dysplasia and sputum atypia; many of these trials have reported conflicting results. Several ongoing multi-institutional trials are evaluating chemoprevention regimens for prevention of second primary aerodigestive tract cancers, the results of which are eagerly awaited. Primary prevention trials to prevent lung cancer have reported sobering results, which negate the protective effects of beta-carotene against lung cancer development and provide no justification for consuming supplemental beta-carotene for cancer chemoprevention. In the future, the use of biomolecular markers as intermediate end points in chemoprevention trials may reduce the cost and time commitment required for these trials and aid in selecting a patient population that would benefit most from chemopreventive intervention or approaches such as gene therapy.

Topics: Anticarcinogenic Agents; beta Carotene; Biomarkers; Carcinogens, Environmental; Chemoprevention; Clinical Trials as Topic; Genetic Markers; Genetic Predisposition to Disease; Humans; Lung Neoplasms; Neoplasms, Second Primary; Retinoids; Risk Factors; Smoking; Vitamin E

A large body of observational epidemiologic studies has consistently demonstrated that individuals who eat more fruits and vegetables, which are rich in carotenoids, and people who have higher serum beta-carotene levels have a lower risk of cancer, particularly lung cancer. In contrast to these observations, two human intervention studies that used high-dose beta-carotene supplements reported an increased risk for lung cancer among smokers. Recently, in vitro and in vivo studies have shed light on the present conundrum regarding the potential chemopreventive activity of beta-carotene; that is, beta-carotene itself may act as an anticarcinogen, but its oxidized products may facilitate carcinogenesis. These studies support the hypothesis that the carcinogenic response to high-dose beta-carotene supplementation reported in the human intervention trials is related to the instability of the beta-carotene molecule in the free radical-rich environment in the lungs of cigarette smokers. This is especially possible because smoke also causes decreased tissue levels of other antioxidants, such as ascorbate and alpha-tocopherol, which normally have a stabilizing effect on the unoxidized form of beta-carotene. Nutritional intervention using a combination of antioxidants (beta-carotene, alpha-tocopherol, and vitamin C) as anticarcinogenic agents could be an appropriate way to rationally and realistically reduce cancer risk.

Topics: Antioxidants; beta Carotene; Diet; Dose-Response Relationship, Drug; Humans; Lung Neoplasms; Signal Transduction; Smoking

Folate is an important cofactor in the transfer of one-carbon moieties and plays a key role in DNA synthesis, repair, and methylation. The role of folate has greatly evolved from the prevention of macrocytic anemia to the prevention of cardiovascular disease and neural tube defects. More recently, epidemiologic, animal, and clinical evidence suggests that folate may also play a role in cancer prevention. Two recently published large, prospective epidemiologic studies suggest that maintaining adequate levels of serum folate or moderately increasing folate intakes from dietary sources and vitamin supplements can significantly reduce the risk of pancreatic and breast cancer, respectively. This protective effect of folate appears to be operative in subjects at risk for developing these cancers, namely, male smokers for pancreatic cancer and women regularly consuming a moderate amount of alcohol for breast cancer. Because the expanding role of folate nutrition in cancer prevention has major public health implications, research is required to clearly elucidate the effect of folate on carcinogenesis.

Topics: Adolescent; Adult; Alcohol Drinking; Animals; beta Carotene; Breast Neoplasms; Case-Control Studies; Female; Folic Acid; Follow-Up Studies; Hematinics; Humans; Lung Neoplasms; Male; Mammary Neoplasms, Experimental; Mice; Middle Aged; Neoplasms; Odds Ratio; Pancreatic Neoplasms; Postmenopause; Premenopause; Prospective Studies; Randomized Controlled Trials as Topic; Rats; Risk; Risk Factors; Smoking; Time Factors; Vitamins

The safety of beta-carotene was reassessed by evaluating the relevant literature on the beneficial and adverse effects of beta-carotene on cancer and, in particular, by evaluating the results of toxicity studies. Beta-carotene appeared neither genotoxic nor reprotoxic or teratogenic, and no signs of organ toxicity have been found in subacute, subchronic, or chronic oral toxicity studies in experimental animals receiving doses of up to 1000 mg/day beta-carotene per kg body weight via the diet. Synthetic beta-carotene did not exert any carcinogenic effect in Sprague-Dawley rats or in CD1 mice. An enhanced risk of lung cancer was found in two human intervention studies. Although dose and (timing of) exposure, smoking status, and imbalance of antioxidant defense have been recognized as potential factors accounting for the outcome of these studies, a conclusive explanation has not yet been found. It is concluded that exposure to beta-carotene resulting in mean plasma concentrations of no more than 2.2 micromol/l (1.2 microg/ml) is safe to the general population. By contrast, in heavy smokers higher plasma concentrations may be associated with a higher lung cancer risk.

Topics: Absorption; Animals; Antioxidants; beta Carotene; Cell Transformation, Neoplastic; Chemoprevention; Drug Interactions; Humans; Lung Neoplasms; Mice; Rats; Rats, Sprague-Dawley; Skin Neoplasms; Smoking

Beta-carotene and retinoids were the most promising agents against common cancers when the National Cancer Institute mounted a substantial program of population-based trials in the early 1980s. Both major lung cancer chemoprevention trials not only showed no benefit, but had significant increases in lung cancer incidence and in cardiovascular and total mortality. A new generation of laboratory research has been stimulated. Rational public health recommendations at this time include: 1. Five-A-Day servings of fruits and vegetables, a doubling of current mean intake; 2. systematic investigation of the covariates of extremes of fruit and vegetable intake; 3. discouragement of beta-carotene supplement use, due to adverse effects in smokers and no evidence of benefit in non-smokers; 4. multilevel research to develop and evaluate candidate chemoprevention agents to prevent lung and other common cancers; and 5. continued priority for smoking prevention, smoking cessation, and avoidance of known carcinogens in the environment.

Topics: Anticarcinogenic Agents; beta Carotene; Chemoprevention; Humans; Lung Neoplasms; Randomized Controlled Trials as Topic; Smoking Cessation; United States; Vitamin A

A critical review of epidemiological studies on diet and lung cancer over the last 20+ years has not provided overwhelming evidence that higher consumption of vegetables, fruit, low-fat/low-cholesterol foods or such micronutrients as carotenoids, selenium and vitamins A, C or E is associated with reduced lung cancer risk. Results from case-control studies have been more positive, with about one half showing fruit and vegetables or their associated micronutrients to be associated with reduced risk. However, most results from cohort and serum micronutrient studies, which avoid the problems of inaccurate accounting of diet and recall bias, were statistically insignificant. Moreover, although most studies were conducted on white male smokers in North America and Europe, the few studies which found significant contrary trends were among subjects of different backgrounds, i.e., black American males and Chinese women in China. Since male smokers vs. nonsmokers in Europe, North America and Japan have been shown in other studies to be lower consumers of fruit/vegetables, and less likely to pursue "perceived healthier lifestyles," the possibility that some of the epidemiological findings on diet and lung cancer are artifactually due to inadequate adjustment for behavioral correlates of smoking and health seekers in a particular society must be considered. This is especially true with recent chemoprevention trials showing higher lung cancer incidence and deaths among consumers of beta-carotene supplements vs. placebo.

Topics: Ascorbic Acid; beta Carotene; Case-Control Studies; Diet; Dietary Fats; Fruit; Humans; Life Style; Lung Neoplasms; Odds Ratio; Risk; Smoking; Vegetables; Vitamin A

The basis for primary prevention of cancer is well-established, because significant causes of cancer are known. However, apart from reducing cigarette smoking, few easily applicable measures to decrease cancer incidence are available. Recently, there has been much interest in chemoprevention in cancer control, with several international bodies, including the International Union Against Cancer (UICC) and the European Union (EU), making important contributions. The results and relevance of these studies are discussed. Many of the problems associated with evaluating cancer prevention strategies generally apply particularly to chemoprevention, and these issues also are addressed.

Topics: Age Distribution; Anticarcinogenic Agents; beta Carotene; Colorectal Neoplasms; Europe; Female; Finland; Humans; Incidence; Lung Neoplasms; Male; Mortality; Neoplasms; Registries; Selenium; Stomach Neoplasms; Vitamin A; Vitamin E

Lung cancer is the leading cause of cancer death in the United States, and advances in therapy have accounted for an improvement in five-year survival in this disease from 9% to 13% over the last three decades. Molecular genetic evidence has confirmed the epidemiologic link between tobacco and lung cancer causation, and has clarified the etiology of the persistent risk of lung cancer development in former smokers. Retinoids have shown promise in aerodigestive cancer chemoprevention, both in the reversal of preneoplastic lesions and in the prevention of second primary cancers. After initial epidemiologic and dietary studies had linked beta-Carotene with cancer risk reduction, large randomized phase III studies of this compound have shown no evidence of benefit and some evidence of heightened lung cancer risk in active smokers on high dose supplemental beta-Carotene. Therefore, careful clinical, epidemiologic, and basic studies of retinoids using intermediate end point markers are necessary to determine the definitive role of these compounds in the chemoprevention of respiratory tract cancer, with a particular focus on former smokers.

Topics: Aged; beta Carotene; Carcinoma; Clinical Trials as Topic; Female; Humans; Lung Neoplasms; Male; Middle Aged; Retinoids; Smoking

Lung cancer is a major contributor to overall cancer mortality. Detecting lung cancer while it is still a localized process is a long-cherished goal for improving the outcome of this disease. Recent developments suggest that we are approaching this capability. We next have to think about how to implement a change in our approach to lung cancer management to derive the benefit of better detection capability. This is an area in which our growing understanding of lung cancer biology is providing clues on improving the inhibition of cancer progression.

Topics: Apoptosis; beta Carotene; Biomarkers, Tumor; Humans; Lung Neoplasms

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Breast Neoplasms; Case-Control Studies; Cohort Studies; Colonic Neoplasms; Diet; Dietary Fats; Ethanol; Female; Fruit; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prospective Studies; Rectal Neoplasms; Risk Factors; Smoking; Stomach Neoplasms; Vegetables; Vitamin E

Clinical trials were designed to validate the protective effect of beta-carotene in populations of cigarette smokers at high risk for lung cancer development. Strikingly, an increase in lung cancer resulted following beta-carotene supplementation in two separate studies in Finland and the United States. These trials were conducted without any evidence that beta-carotene prevents lung cancer in animal models.

Topics: Aged; Animals; beta Carotene; Clinical Trials as Topic; Female; Finland; Humans; Lung Neoplasms; Male; Middle Aged; Smoking; United States

Topics: beta Carotene; Carotenoids; Fruit; Humans; Lung Neoplasms; Neoplasms; Smoking; Vegetables

Topics: beta Carotene; Humans; Lung Neoplasms; Primary Prevention; Risk Factors; Treatment Outcome

Epidemiologic evidence on the relationship between nutrition and lung cancer is reviewed. Observational studies of diet and lung cancer, both prospective and retrospective, continue to suggest strongly that increased vegetable and fruit intake is associated with reduced risk in men and women; in various countries; in smokers, ex-smokers, and never-smokers; and for all histologic types of lung cancer. Prospective studies of blood beta-carotene levels, arguably the best available biomarker of vegetable and fruit intake, indicate that low levels are predictive of increased lung cancer incidence. However, in a randomized, placebo-controlled clinical trial in male smokers, lung cancer incidence and total mortality were increased significantly among the men receiving beta-carotene supplements. If beta-carotene can prevent lung carcinogenesis, which the trial cannot rule out, then the dosage, duration of use, method of administration, and/or subpopulation are critical. Ongoing clinical trials, some of which include women, will provide much-needed information. Other carotenoids, other phytochemicals, and associated dietary patterns may explain the beneficial effects of vegetables and fruits and have not been explored adequately in epidemiologic work. Several observational epidemiologic studies, both prospective and retrospective, have indicated that diets high in fat, saturated fat, and cholesterol may increase the risk of lung cancer and that the effect is not mediated through vegetable and fruit intake. The relationship, although not yet established, merits further investigation. Since beta-carotene can function as an antioxidant, other micronutrients with this potential, specifically vitamins E and C and selenium, also have been proposed to reduce lung cancer risk. However, the totality of the epidemiologic evidence is not, at present, persuasive for any one of these micronutrients.

Topics: beta Carotene; Carotenoids; Cholesterol, Dietary; Diet; Dietary Fats; Fatty Acids; Feeding Behavior; Female; Forecasting; Fruit; Humans; Incidence; Lung Neoplasms; Male; Nutritional Physiological Phenomena; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Smoking; Vegetables

Cancer is currently regarded to be the phenotypic expression of an accumulation of heritable alterations in the regulators of cell growth and differentiation. Though detailed knowledge of the sequence and in vivo mechanistic effects of these alterations is rudimentary for most, if not all, cancers, their identification does offer the potential for classifying groups of individuals who are heterogeneous with respect to their cancer risks, into more nearly homogeneous subgroups. In this paper, we illustrate the value of using markers, which we define as any manifestation of cellular molecular diversity, to increase subgroup homogeneity. In the context of time-to-event data, we demonstrate for both somatic mutations (acquired p53 abnormalities in gastric mucosal cells) and inherited polymorphisms (polymorphisms in the phase 1 and 2 detoxifying enzymes) how knowledge regarding the population frequency of the marker the effect of the marker on the risk of cancer development, and/or the effect of the marker on response to therapy, can be used to plan and analyze such trials. Using as paradigms demographic features of the recently begun Shandong precancerous gastric lesion intervention trial, and the recently completed alpha-tocopherol beta-carotene (ATBC) lung cancer prevention study, we review the information, assumptions, and mathematical structure required for planning cancer prevention trials. We graphically demonstrate how informative markers make available strategies for selection, stratification, and optimal weighing, which, when properly implemented, increase the power of tests of effective cancer prevention agents.

Topics: Adult; Aged; beta Carotene; Biomarkers, Tumor; China; Clinical Trials as Topic; Cohort Studies; Finland; Humans; Japan; Lung Neoplasms; Male; Middle Aged; Mutagenesis; Neoplasms; Polymorphism, Genetic; Research Design; Stomach Neoplasms; Vitamin E

Topics: beta Carotene; Humans; Lung Neoplasms

Treatment of lung cancer remains frustrating. Most patients with lung cancer are not candidates for curative therapy, and new therapies have not made a substantial impact on survival. Consequently, some clinical investigators have focused their efforts on developing prevention strategies. Chemoprevention, the administration of agents to block or reverse carcinogenesis, is being investigated in ongoing trials. Studies of chemoprevention in lung cancer have included trials to reverse premalignant lesions such as sputum atypia or squamous metaplasia of the bronchial epithelium. Clinical trials of lung cancer prevention have often studied groups of participants with tobacco or asbestos exposure. Other clinical trials are being conducted among patients who have been treated for an early-stage lung cancer. As the result of diffuse epithelial injury, these patients are at very high risk for developing second primary tumors, predominantly in the lungs and upper aerodigestive tract. It is our hope that these studies may establish a new strategy for preventing lung cancer.

Topics: Anticarcinogenic Agents; beta Carotene; Carcinoma, Non-Small-Cell Lung; Carotenoids; Clinical Trials as Topic; Humans; Isotretinoin; Lung Neoplasms; Neoplasms, Second Primary; Precancerous Conditions; Randomized Controlled Trials as Topic

Topics: Animals; Antioxidants; Artifacts; beta Carotene; Breast Neoplasms; Carotenoids; Case-Control Studies; Cohort Studies; Diet; Digestive System Neoplasms; Female; Genital Neoplasms, Female; Humans; Lung Neoplasms; Neoplasms; Neoplasms, Experimental; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Sampling Studies; Urogenital Neoplasms; Vitamin A; Vitamin E; Vitamins

Topics: beta Carotene; Carotenoids; Clinical Trials as Topic; Diet; Esophageal Neoplasms; Fruit; Humans; Lung Neoplasms; Male; Neoplasms; Risk Factors; Stomach Neoplasms; Vegetables; Vitamins

Topics: Asbestos; beta Carotene; Carotenoids; Genetic Markers; Health Education; Humans; Lung Neoplasms; Radon; Retinoids; Smoking; Smoking Cessation; Vitamins

Chemoprevention entails using specific agents to suppress carcinogenesis and thereby prevent the development of primary or second primary cancers. Because the concept of chemoprevention in patients with or at risk of lung cancer is new, ongoing clinical trials are based on data from epidemiologic and preclinical research, as well as on results of chemoprevention studies in head and neck cancer. The latter studies have provided a model for such studies in lung cancer, considering the two diseases have a similar etiology and biology of field carcinogenesis. Beta-carotene, natural vitamin A, and the retinoids may be effective chemopreventive agents. However, chronic administration of such agents may be required to prevent the development of cancer. Results of chemoprevention trials in head and neck cancer have demonstrated effective inhibition of the development of second primary tumors with the synthetic retinoid 13-cis-retinoic acid; investigators are hopeful this will be repeated in patients with lung cancer. Results of ongoing phase III trials and continued advances in the epidemiologic and biologic study of lung carcinogenesis should contribute to future research in this area.

Topics: beta Carotene; Carotenoids; Head and Neck Neoplasms; Humans; Isotretinoin; Leukoplakia, Oral; Lung Neoplasms; Neoplasms, Second Primary; Risk Factors; Vitamin A

The incidence of lung cancer in the United States has stabilized in recent years, but it remains a major cause of death in the United States. Whereas the single most effective primary prevention of this disease would be to eliminate tobacco use from society, this is currently an unrealistic goal. Secondary prevention, however--that is, chemoprophylactic treatment of smokers, exsmokers, and others at risk--represents a viable option. Agents proven effective in both laboratory models and humans include vitamin A and its synthetic derivatives, the retinoids and the carotenoids. It is fairly easy to identify patients at risk of lung cancer compared with other cancers. Yet aside from patients who are under a physician's care and aware of their risk, it can be difficult to target individuals for chemoprophylactic treatment, especially those who are healthy but at high risk and not seeing a physician or other health care provider. Screening for the presence of predictive cellular and molecular changes may facilitate more accurate selection of individuals for chemoprophylactic treatment.

Topics: Aged; beta Carotene; Carotenoids; Female; Humans; Lung Neoplasms; Male; Middle Aged; Risk Factors; Smoking Prevention; Vitamin A

Exposure to benzopyrene, an enzyme-inducing PAH carcinogen, promotes vitamin A depletion in exposed tissues. This effect is evident while on a vitamin A sufficient diet and without a decline in serum retinol. The finding of local tissue vitamin depletion without systemic depletion may have considerable implications in maintaining tissue health. While the described studies involved dietary exposure to benzopyrene, it is reasonable to extrapolate that inhalation exposure via cigarette smoke would have a similar effect in the lungs and perhaps stomach and bladder. Higher MFO enzyme activity in the lungs may have detrimental effects. Kellermann's early work identifying a higher incidence of lung cancer in those with genetically greater aryl hydrocarbon hydroxylase activity was interpreted as due to the greater formation of a reactive intermediate in the process of carcinogen metabolism. As an alternative hypothesis I suggest that those with higher enzyme inducibility may have greater carcinogen-induced vitamin A depletion. If poor tissue vitamin A nutriture potentiates the carcinogenicity of compounds such as benzopyrene, dietary or pharmacologic interventions which improve tissue nutriture could be important. The demonstrated effect of dietary beta-carotene on preventing carcinogen-induced tissue vitamin A depletion suggests one mechanism by which beta-carotene may be cancer protective. Further investigations are warranted, particularly with inhalation exposure to carcinogens and the effect of dietary beta-carotene on lung tissue nutriture.

Topics: Animals; Benzopyrenes; beta Carotene; Carotenoids; Female; Liver; Lung; Lung Neoplasms; Nicotiana; Plants, Toxic; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Smoke; Vitamin A; Vitamin A Deficiency

The recent findings are critically reviewed on metabolism, pharmacokinetics, both nutritional and biochemical epidemiology, and the probable mechanisms of chemopreventive action. Some recommendations of practical value are highlighted.

Topics: beta Carotene; Carotenoids; Diet; Humans; Lung Neoplasms; Risk Factors

Carotenoid (CARs: beta-carotene BC and/or canthaxanthin CX) supplementation have been shown to be chemopreventive in animals, since 1980, against direct or indirect chemical carcinogenesis/photo-carcinogenesis of the skin, breast, stomach, salivary glands, colon-rectum, urinary bladder, and against transplanted tumors. This action could be either independent of or dependent on pro-vitamin A activity of BC. In vitro, both BC and CX proved to be antimutagenic and to have anti-malignant transformation properties in cell cultures. Preliminary interventions in humans with BC +/- CX prevented the onset of second primary tumors in lung, colon, urinary bladder, and head and neck. The powerful antioxidant properties of CARs, possibly associated with their retinoid potential, played a role in all the above observations, producing free-radical quenching and immunostimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antibody Formation; beta Carotene; Breast Diseases; Carotenoids; Humans; Lung Neoplasms; Neoplasms; Vitamin A

Cancer chemoprevention research takes leads from epidemiologic and laboratory research and develops them through in vitro and in vivo preclinical research and initial human studies into randomized controlled clinical trials. At present, the chemoprevention program is sponsoring 21 human efficacy studies. These trials are testing the potential of agents (beta-carotene, folic acid, 13-cis retinoic acid, 4-hydroxyphenyl retinamide, vitamins C and E, and minerals) as inhibitors of a variety of cancers in humans (colon, lung, esophagus, cervix, bladder, and skin). Endpoints in these studies include overall incidence of cancer, incidence of specific cancers, rate of regression or progression of preneoplastic changes, and changes in cellular or biochemical parameters. Study participants include volunteers from the general population; populations at high risk for cancer because of occupation, lifestyle, or place of residence; persons with previously treated cancers; and persons with preneoplastic lesions. Study designs include single agent randomization, combination of agents and complete factorial designs.

Topics: Animals; Antioxidants; beta Carotene; Carotenoids; Clinical Trials as Topic; Disease Models, Animal; Humans; Lung Neoplasms; Neoplasms; Neoplasms, Experimental; Randomized Controlled Trials as Topic; Vitamin A

In a dozen case-control and cohort studies, high intake of fruits and vegetables containing carotenoids has been associated with a reduced risk of lung cancer. In contrast, little relation has been found between intake of preformed vitamin A and this disease. Although initial studies suggested that persons with lower levels of serum retinol have higher future rates of lung cancer, this idea was not confirmed in subsequent investigations. Prediagnostic levels of beta-carotene in blood, however, have been inversely related with risk of lung cancer. Available data thus strongly support the hypothesis that dietary carotenoids reduce the risk of lung cancer, but the data are also compatible with the possibility that some other factor in these foods is responsible for the lower risk. Even if ultimately shown to be casual, the relation between diet and lung cancer is modest compared with the deleterious effect of cigarette smoking.

Topics: beta Carotene; Carotenoids; Case-Control Studies; Cohort Studies; Diet; Fruit; Humans; Lung Neoplasms; Risk Factors; Smoking; Vegetables; Vitamin A

Topics: Animals; Antineoplastic Agents; beta Carotene; Carotenoids; Clinical Trials as Topic; Diet Therapy; Humans; Lung Neoplasms; Trace Elements; Vitamins

Topics: beta Carotene; Carotenoids; Diet; Humans; Lung Neoplasms; Risk Factors

After the Age-Related Eye Disease Study 2 (AREDS2) study, the beta carotene component was replaced by lutein/zeaxanthin for the development of the revised AREDS supplement. However, it is unknown if the increased risk of lung cancer observed in those assigned beta carotene persists beyond the conclusion of the AREDS2 trial and if there is a benefit of adding lutein/zeaxanthin to the original AREDS supplement that can be observed with long-term follow-up.. To assess 10-year risk of developing lung cancer and late age-related macular degeneration (AMD).. This was a multicenter epidemiologic follow-up study of the AREDS2 clinical trial, conducted from December 1, 2012, to December 31, 2018. Included in the analysis were participants with bilateral or unilateral intermediate AMD for an additional 5 years after clinical trial. Eyes/participants were censored at the time of late AMD development, death, or loss to follow-up. Data were analyzed from November 2019 to March 2022.. During the clinical trial, participants were randomly assigned primarily to lutein/zeaxanthin and/or ω-3 fatty acids or placebo and secondarily to no beta carotene vs beta carotene and low vs high doses of zinc. In the epidemiologic follow-up study, all participants received AREDS2 supplements with lutein/zeaxanthin, vitamins C and E, and zinc plus copper. Outcomes were assessed at 6-month telephone calls. Analyses of AMD progression and lung cancer development were conducted using proportional hazards regression and logistic regression, respectively.. Self-reported lung cancer and late AMD validated with medical records.. This study included 3882 participants (mean [SD] baseline age, 72.0 [7.7] years; 2240 women [57.7%]) and 6351 eyes. At 10 years, the odds ratio (OR) of having lung cancer was 1.82 (95% CI, 1.06-3.12; P = .02) for those randomly assigned to beta carotene and 1.15 (95% CI, 0.79-1.66; P = .46) for lutein/zeaxanthin. The hazard ratio (HR) for progression to late AMD comparing lutein/zeaxanthin with no lutein/zeaxanthin was 0.91 (95% CI, 0.84-0.99; P = .02) and comparing ω-3 fatty acids with no ω-3 fatty acids was 1.01 (95% CI, 0.93-1.09; P = .91). When the lutein/zeaxanthin main effects analysis was restricted to those randomly assigned to beta carotene, the HR was 0.80 (95% CI, 0.68-0.92; P = .002). A direct analysis of lutein/zeaxanthin vs beta carotene showed the HR for late AMD was 0.85 (95% CI, 0.73-0.98; P = .02). The HR for low vs high zinc was 1.04 (95% CI, 0.94-1.14; P = .49), and the HR for no beta carotene vs beta carotene was 1.04 (95% CI, 0.94-1.15; P = .48).. Results of this long-term epidemiologic follow-up study of the AREDS2 cohort suggest that lutein/zeaxanthin was an appropriate replacement for beta carotene in AREDS2 supplements. Beta carotene usage nearly doubled the risk of lung cancer, whereas there was no statistically significant increased risk with lutein/zeaxanthin. When compared with beta carotene, lutein/zeaxanthin had a potential beneficial association with late AMD progression.

Topics: Aged; beta Carotene; Dietary Supplements; Fatty Acids, Omega-3; Female; Follow-Up Studies; Humans; Lung Neoplasms; Macular Degeneration; Zeaxanthins; Zinc

Retinol, the most biologically active form of vitamin A, might influence cancer-related biological pathways. However, results from observational studies of serum retinol and cancer risk have been mixed. We prospectively examined serum retinol and risk of overall and site-specific cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 29,104 men), conducted in 1985-1993, with follow-up through 2012. Serum retinol concentration was measured using reverse-phase high-performance liquid chromatography. Cox proportional hazards models estimated the association between baseline serum retinol quintile and overall and site-specific cancer risk in 10,789 cases. After multivariable adjustment, higher serum retinol was not associated with overall cancer risk (highest vs. lowest quintile: hazard ratio (HR) = 0.97, 95% confidence interval (CI): 0.91, 1.03; P for trend = 0.43). Higher retinol concentrations were, however, associated with increased risk of prostate cancer (highest vs. lowest quintile: HR = 1.28, 95% CI: 1.13, 1.45; P for trend < 0.0001) and lower risk of both liver and lung cancers (highest vs. lowest quintile: for liver, HR = 0.62, 95% CI: 0.42, 0.91; P for trend = 0.004; and for lung, HR = 0.80, 95% CI: 0.72, 0.88; P for trend < 0.0001). No associations with other cancers were observed. Understanding the mechanisms that underlie these associations might provide insight into the role of vitamin A in cancer etiology.

Topics: Aged; Alcohol Drinking; alpha-Tocopherol; beta Carotene; Body Weights and Measures; Cholesterol, HDL; Chromatography, High Pressure Liquid; Diet; Dietary Supplements; Double-Blind Method; Exercise; Finland; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Prostatic Neoplasms; Residence Characteristics; Smoking; Socioeconomic Factors

The aim of this study was to investigate the association between BMI (kg/m) and prostate cancer risk. BMI is a modifiable lifestyle factor and may provide a unique opportunity for primary prevention of prostate cancer if a causal association exists. Data from 11 886 men from the Carotene and Retinol Efficacy Trial (CARET, 1985-1996 with active follow-up through 2005) comprising current and former heavy smokers were analyzed. CARET was a multicenter randomized, double-blind placebo-controlled chemoprevention trial testing daily supplementation of 30 mg β-carotene+25 000 IU retinyl palmitate for primary prevention of lung cancer. Prostate cancer was a secondary outcome. Nonaggressive disease was defined as Gleason less than 7 and stage I/II. Aggressive disease was primarily defined as at least Gleason 7 or stage III/IV, and secondarily by excluding Gleason 3+4 from the first definition. BMI was calculated from measured weight and height. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for cancer incidence between BMI categories. During follow-up, 883 men were diagnosed with prostate cancer. In the analysis of aggressive disease when Gleason 3+4 was excluded, men with a BMI of at least 35 kg/m had an increased rate of prostate cancer (HR: 1.80, 95% CI: 1.04-3.11, Ptrend=0.04) compared with men with BMI 18-24.9 kg/m. No other differences were seen in risk estimates for overall, nonaggressive or aggressive prostate cancer including all Gleason 7 cases, between BMI categories. Our results show an association between having a BMI of at least 35 kg/m and an increased risk of aggressive prostate cancer (not including Gleason 3+4 tumors), but do not support an association between BMI and risk of overall, aggressive disease including all Gleason 7, or nonaggressive prostate cancer within a population of current and former heavy smokers.

Topics: Aged; beta Carotene; Body Mass Index; Double-Blind Method; Female; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Prognosis; Prostatic Neoplasms; Provitamins; Risk Factors; United States; Vitamin A; Vitamins

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study demonstrated that β-carotene supplementation increases lung cancer incidence in smokers. Further, cigarettes with higher tar and nicotine content are associated with a higher risk of lung cancer. However, no studies have examined whether the increased risk associated with β-carotene supplementation in smokers varies by the tar or nicotine content of cigarettes.. The ATBC Study was a randomized, double-blind intervention trial conducted in southwest Finland. A total of 29 133 male smokers, aged 50-69 years, were enrolled and randomly assigned to one of four groups (α-tocopherol, β-carotene, both, or placebo). Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of lung cancer risk by β-carotene trial assignment stratified by a priori categories of cigarette tar and nicotine content.. The β-carotene supplementation group had significantly higher risk of developing lung cancer in all categories of tar content (yes vs. no β-carotene supplementation-ultralight cigarettes [≤7 mg tar]: HR = 1.31, 95% CI = 0.91 to 1.89; nonfiltered cigarettes [≥21 mg tar]: HR = 1.22, 95% CI = 0.91 to 1.64; p for interaction = .91). Similarly, there was no interaction with nicotine content (yes vs. no β-carotene supplementation-ventilated cigarettes [≤0.8 µg nicotine]: HR = 1.23, 95% CI = 0.98 to 1.54; nonfiltered cigarettes [≥1.3 µg nicotine]: HR = 1.22, 95% CI = 0.91 to 1.64; p for interaction = .83).. These findings support the conclusion that supplementation with β-carotene increases the risk of lung cancer in smokers regardless of the tar or nicotine content of cigarettes smoked. Our data suggest that all smokers should continue to avoid β-carotene supplementation.. Previous studies demonstrated that β-carotene supplementation increases risk of lung cancer in smokers. This study moves the field forward by examining the potential for modification of risk of lung cancer with different levels of tar and nicotine in cigarettes smoked, as interaction with carcinogens in these components of cigarette smoke is hypothesized to be the mechanism by which β-carotene increases risk. Our study provides evidence that the increased risk of lung cancer in smokers who take β-carotene supplements is not dependent upon the tar or nicotine level of cigarettes smoked and suggests that all smokers should continue to avoid β-carotene supplementation.

Topics: Aged; alpha-Tocopherol; Antioxidants; beta Carotene; Dietary Supplements; Double-Blind Method; Finland; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Nicotine; Provitamins; Smoking; Tars

The neutrophil-to-lymphocyte ratio (NLR) is a biomarker that indicates systemic inflammation and can be estimated using array-based DNA methylation data as methylation-derived NLR (mdNLR). We assessed the relationship between prediagnosis mdNLR and lung cancer risk in a nested case-control study in the β-Carotene and Retinol Efficacy Trial (CARET) of individuals at high risk for lung cancer due to heavy smoking or substantial occupational asbestos exposure. We matched 319 incident lung cancer cases to controls based on age at blood draw, smoking, sex, race, asbestos, enrollment year, and time at risk. We computed mdNLR using the ratio of predicted granulocyte and lymphocyte proportions derived from DNA methylation signatures in whole blood collected prior to diagnosis (median 4.4 years in cases). Mean mdNLR was higher in cases than controls (2.06 vs. 1.86,

Topics: Aged; Asbestos; beta Carotene; Carcinoma, Non-Small-Cell Lung; Case-Control Studies; Diterpenes; DNA Methylation; Female; Humans; Inflammation; Lung Neoplasms; Lymphocyte Count; Lymphocytes; Male; Middle Aged; Neutrophils; Occupational Exposure; Oligonucleotide Array Sequence Analysis; Retinyl Esters; Risk Factors; Smokers; Smoking; Vitamin A

Oral supplementation with the Age-Related Eye Disease Study (AREDS) formulation (antioxidant vitamins C and E, beta carotene, and zinc) has been shown to reduce the risk of progression to advanced age-related macular degeneration (AMD). Observational data suggest that increased dietary intake of lutein + zeaxanthin (carotenoids), omega-3 long-chain polyunsaturated fatty acids (docosahexaenoic acid [DHA] + eicosapentaenoic acid [EPA]), or both might further reduce this risk.. To determine whether adding lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation decreases the risk of developing advanced AMD and to evaluate the effect of eliminating beta carotene, lowering zinc doses, or both in the AREDS formulation.. The Age-Related Eye Disease Study 2 (AREDS2), a multicenter, randomized, double-masked, placebo-controlled phase 3 study with a 2 × 2 factorial design, conducted in 2006-2012 and enrolling 4203 participants aged 50 to 85 years at risk for progression to advanced AMD with bilateral large drusen or large drusen in 1 eye and advanced AMD in the fellow eye.. Participants were randomized to receive lutein (10 mg) + zeaxanthin (2 mg), DHA (350 mg) + EPA (650 mg), lutein + zeaxanthin and DHA + EPA, or placebo. All participants were also asked to take the original AREDS formulation or accept a secondary randomization to 4 variations of the AREDS formulation, including elimination of beta carotene, lowering of zinc dose, or both.. Development of advanced AMD. The unit of analyses used was by eye.. Median follow-up was 5 years, with 1940 study eyes (1608 participants) progressing to advanced AMD. Kaplan-Meier probabilities of progression to advanced AMD by 5 years were 31% (493 eyes [406 participants]) for placebo, 29% (468 eyes [399 participants]) for lutein + zeaxanthin, 31% (507 eyes [416 participants]) for DHA + EPA, and 30% (472 eyes [387 participants]) for lutein + zeaxanthin and DHA + EPA. Comparison with placebo in the primary analyses demonstrated no statistically significant reduction in progression to advanced AMD (hazard ratio [HR], 0.90 [98.7% CI, 0.76-1.07]; P = .12 for lutein + zeaxanthin; 0.97 [98.7% CI, 0.82-1.16]; P = .70 for DHA + EPA; 0.89 [98.7% CI, 0.75-1.06]; P = .10 for lutein + zeaxanthin and DHA + EPA). There was no apparent effect of beta carotene elimination or lower-dose zinc on progression to advanced AMD. More lung cancers were noted in the beta carotene vs no beta carotene group (23 [2.0%] vs 11 [0.9%], nominal P = .04), mostly in former smokers.. Addition of lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation in primary analyses did not further reduce risk of progression to advanced AMD. However, because of potential increased incidence of lung cancer in former smokers, lutein + zeaxanthin could be an appropriate carotenoid substitute in the AREDS formulation.. clinicaltrials.gov Identifier: NCT00345176.

Topics: Aged; beta Carotene; Dietary Supplements; Disease Progression; Docosahexaenoic Acids; Double-Blind Method; Drug Therapy, Combination; Eicosapentaenoic Acid; Female; Humans; Incidence; Lung Neoplasms; Lutein; Macular Degeneration; Male; Middle Aged; Risk; Treatment Outcome; Vitamins; Xanthophylls; Zeaxanthins; Zinc

Our prior studies of lung cancer suggested that a novel biomarker (pro-surfactant protein B or pro-SFTPB) might serve as a predictive marker for this disease. We aimed to determine the potential use of pro-SFTPB for distinguishing lung cancer cases from matched controls as a risk marker.. Study subjects were drawn from the longitudinal Physicians' Health Study (PHS). Cases (n = 188) included individuals who were cancer-free at study enrollment but developed lung cancer during follow-up. Controls (n = 337) were subjects who did not develop lung cancer. Cases and controls were matched on date of study enrollment, age at enrollment, and smoking status and amount. Baseline plasma samples drawn at enrollment were analyzed for pro-SFTPB using ELISA to detect differences in protein expression levels for cases and controls.. Pro-SFTPB nondetectable status was significantly associated with lung cancer risk [OR = 5.88; 95% confidence interval (CI) 1.24-27.48]. Among subjects with detectable levels of the protein, increasing plasma concentration of pro-SFTPB was associated with higher lung cancer risk (OR = 1.41 per unit increase in log pro-SFTPB; 95% CI 1.08-1.84).. These results suggest a nonlinear, J-shaped association between plasma pro-SFTPB levels and lung cancer risk, with both nondetectable and higher levels of the marker being associated with lung cancer.. These results show promise of a risk marker that could contribute to predicting risk for lung cancer development and to narrowing the high-risk population for low-dose computed tomography screening.

Topics: beta Carotene; Biomarkers, Tumor; Case-Control Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Receptors, Fc; Risk Factors; Vitamins

Uncertainty remains over whether or not high intakes of retinol or vitamin A consumed through food or supplements may increase fracture risk. This intervention study found no increase in fracture risk among 2,322 adults who took a controlled, high-dose retinol supplement (25,000 IU retinyl palmitate/day) for as long as 16 years. There was some evidence that beta-carotene supplementation decreased fracture risk in men.. There is conflicting epidemiological evidence regarding high intakes of dietary or supplemental retinol and an increased risk for bone fracture. We examined fracture risk in a study administering high doses of retinol and beta-carotene (BC) between 1990 and 2007.. The Vitamin A Program was designed to test the efficacy of retinol and BC supplements in preventing malignancies in persons previously exposed to blue asbestos. Participants were initially randomised to 7.5 mg retinol equivalents (RE)/day as retinyl palmitate, 30 mg/day BC or 0.75 mg/day BC from 1990 to 1996; after which, all participants received 7.5 mg RE/day. Fractures were identified by questionnaire and hospital admission data up until 2006. Risk of any fracture or osteoporotic fracture according to cumulative dose of retinol and BC supplementation was examined using conditional logistic regression models adjusting for age, sex, smoking, body mass index, medication use and previous fracture.. Supplementation periods ranged from 1 to 16 years. Of the 2,322 (664 females and 1,658 males) participants, 187 experienced 237 fractures. No associations were observed between cumulative dose of retinol and risk for any fracture (OR per 10 g RE=0.83; 95% CI, 0.63-1.08) or osteoporotic fracture (OR per 10 g RE=0.95; 95% CI 0.64-1.40). Among men, cumulative dose of BC was associated with a slightly reduced risk of any fracture (OR per 10 g=0.89; 95% CI 0.81-0.98) and osteoporotic fracture (OR per 10 g=0.84; 95% CI 0.72-0.97).. This study observed no increases in fracture risk after long-term supplementation with high doses of retinol and/or beta-carotene.

Topics: Adult; Aged; beta Carotene; Dietary Supplements; Diterpenes; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Occupational Diseases; Osteoporotic Fractures; Retinyl Esters; Risk Assessment; Vitamin A; Western Australia

Lung cancer and tuberculosis cause significant morbidity and mortality worldwide. Tuberculosis may increase lung cancer risk through substantial and prolonged pulmonary inflammation. However, prospective data on tuberculosis and lung cancer risk are limited.. Our study included 29,133 Finnish male smokers followed prospectively in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1985-2005). Lung cancers were identified through linkage with the Finnish Cancer Registry, and hospital-treated tuberculosis cases were ascertained from the National Hospital Discharge Register. We assessed the association between tuberculosis and lung cancer risk with proportional hazards regression models, adjusting for age and cigarette smoking.. Forty-four lung cancer cases occurred among 273 men with tuberculosis (incidence rate = 1,786 per 100,000 person-years). Tuberculosis was associated with a two-fold elevation in lung cancer risk (HR = 1.97; 95% CI = 1.46-2.65) with significant associations observed for both incident (HR = 2.05; 95% CI = 1.42-2.96) and prevalent tuberculosis (HR = 1.82; 95% CI = 1.09-3.02). Lung cancer risk was greatest in the 2-year window after tuberculosis diagnosis (HR = 5.01; 95% CI = 2.96-8.48) but remained elevated at longer latencies (HR = 1.53; 95% CI = 1.07-2.20). Though tuberculosis was associated with an increased risk of squamous cell carcinoma (HR = 3.71), adenocarcinoma (HR = 1.71), small cell carcinoma (HR = 1.72), and lung cancer of other (HR = 1.23) and unknown histologies (HR = 1.35), only the association for squamous cell carcinoma was statistically significant.. Tuberculosis is associated with increased lung cancer risk in male smokers.. Our results add to the growing body of evidence implicating chronic inflammation and pulmonary scarring in the etiology of lung cancer.

Topics: Aged; alpha-Tocopherol; beta Carotene; Double-Blind Method; Finland; Humans; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Risk Factors; Smoking; Tuberculosis

Vitamin E and beta-carotene affect the immune function and might influence the predisposition of man to infections. To examine whether vitamin E or beta-carotene supplementation affects tuberculosis risk, we analysed data of the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC)Study, a randomised controlled trial which examined the effects of vitamin E (50 mg/d) and beta-carotene (20 mg/d) on lung cancer. The trial was conducted in the general community in Finland in 1985-93; the intervention lasted for 6.1 years (median). The ATBC Study cohort consists of 29,023 males aged 50-69 years, smoking at baseline, with no tuberculosis diagnosis prior to randomisation. Vitamin E supplementation had no overall effect on the incidence of tuberculosis (risk ratio (RR) = 1.18; 95% CI 0.87, 1.59) nor had beta-carotene (RR = 1.07; 95% CI 0.80, 1.45). Nevertheless, dietary vitamin C intake significantly modified the vitamin E effect. Among participants who obtained 90 mg/d or more of vitamin Cin foods (n 13,502), vitamin E supplementation increased tuberculosis risk by 72 (95% CI 4, 185)%. This effect was restricted to participants who smoked heavily. Finally, in participants not supplemented with vitamin E, dietary vitamin C had a negative association with tuberculosis risk so that the adjusted risk was 60 (95% CI 16, 81)% lower in the highest intake quartile compared with the lowest. Our finding that vitamin E seemed to transiently increase the risk of tuberculosis in those who smoked heavily and had high dietary vitamin C intake should increase caution towards vitamin E supplementation for improving the immune system.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Diet; Dietary Supplements; Follow-Up Studies; Fruit; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Risk Assessment; Smoking; Tuberculosis; Vegetables; Vitamin E; Vitamins

We assessed whether spirometric measurements are associated with the development of accelerated FEV(1) decline and lung cancer among active and previous smokers with a wide range of lung function. Bivariate and multivariate analyses that adjusted for age, intervention arm, smoking status at enrollment and smoking history, years exposed to asbestos, and evidence of asbestosis were used to assess whether baseline FEV(1) and FEV(1)/FVC ratio were associated with accelerated FEV(1) decline and incident lung cancer. The 3,041 participants enrolled from 1985 to 1994 were followed through April 30, 2005. Baseline FEV(1)/FVC ratio<0.7 was significantly associated with an increased risk for rapid lung function decline (OR=1.73; 95% CI 1.31-2.28; p<0.001). Baseline FEV(1)/FVC ratio<0.7 was also significantly associated with an increased risk of developing lung cancer, even when baseline FEV(1) was >80%. Lung cancer risk among participants with baseline airflow obstruction and FEV(1)<60% was 4-fold higher than participants without baseline airflow obstruction and FEV(1)>80% (p<0.001), even among former smokers. These data indicate an FEV(1)/FVC<0.7 among smokers is significantly associated with faster airflow loss, and an increased risk for developing lung cancer, even among those individuals with a normal FEV(1).

Topics: Aged; Asbestos; beta Carotene; Double-Blind Method; Environmental Exposure; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Pilot Projects; Prognosis; Risk Factors; Smoking; Spirometry; Vitamin A; Vitamins

In vitro and animal studies suggest that antitumor effect of chemotherapeutic agents may be enhanced by antioxidants. Therefore, we initiated a clinical study to test the efficacy of high-dose multiple antioxidants (vitamins C, E and beta carotene) as an adjunct to chemotherapy (paclitaxel and carboplatin) in non-small-cell lung cancer.. 136 patients of stage IIIb and stage IV NSCLC were randomized to receive chemotherapy (paclitaxel and carboplatin) alone (chemotherapy arm, n = 72) or chemotherapy in combination with ascorbic acid 6100 mg/day, dl-alpha-tocopherol (vitamin E) 1050 mg/day and beta-carotene 60 mg/day (combination arm, n = 64). Survival were calculated by the Kaplan-Meier method and compared using the log-rank test.. An overall response rate (RR) of 33% was observed in chemotherapy arm with 24 patients showing a partial response (PR) and none showing a complete response (CR). In combination arm the overall RR was 37% with 24 patients showing PR and two showing CR. The median survival times in chemotherapy arm and combination arm were nine and 11 months respectively. The overall survival (OS) rates in chemotherapy arm and combination arm at one year were 32.9% and 39.1%, and at two years, 11.1% and 15.6% respectively. None of these differences were statistically significant (p = 0.20). Toxicity profiles were similar in both arms.. These results do not support the concern that antioxidants might protect cancer cells from the free radical damage induced by chemotherapy. Larger trials are needed to demonstrate whether high-dose multiple antioxidants in conjunction with chemotherapy increase the response rates and/or survival time in advanced lung cancer.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Ascorbic Acid; beta Carotene; Carcinoma, Non-Small-Cell Lung; Drug Synergism; Female; Humans; Lung Neoplasms; Male; Middle Aged; Survival Analysis; Vitamin E

Despite numerous published studies, debate continues regarding the risk of developing lung cancer among men exposed occupationally to asbestos, particularly those without radiographic or functional evidence of asbestosis. The beta-Carotene and Retinol Efficacy Trial (CARET), a study of vitamin supplementation for chemoprevention of lung cancer, has followed 4,060 heavily exposed US men for 9-17 years. Lung cancer incidence for 1989-2002 was analyzed using a stratified proportional hazards model. The study confirmed excessive rates of lung cancer among men with radiographic asbestosis. Comparison of study arms revealed a strong, unanticipated synergy between radiographic profusion category and the active intervention. In the large subgroup of men with normal lung parenchyma on chest radiograph at baseline, there was evidence of exposure-related lung cancer risk: Men with more than 40 years' exposure in high-risk trades had a risk approximately fivefold higher than men with 5-10 years, after adjustment for covariates. The effect in these men was independent of study intervention arm, but pleural plaques on the baseline radiograph and abnormal baseline flow rate were strong independent predictors of subsequent lung cancer. Residual confounding by subclinical asbestosis, exposure to unmeasured lung carcinogens, or differences in smoking are unlikely to explain these observations better than a carcinogenic effect of asbestos per se.

Topics: Adult; Aged; Anticarcinogenic Agents; Asbestosis; beta Carotene; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Occupational Diseases; Occupational Exposure; Predictive Value of Tests; Proportional Hazards Models; Radiography, Thoracic; Risk Factors; Smoking; Spirometry; United States; Vitamin A

Vitamin E and beta-carotene affect various measures of immune function and accordingly might influence the predisposition of humans to infections. However, only few controlled trials have tested this hypothesis.. To examine whether vitamin E or beta-carotene supplementation affects the risk of pneumonia in a controlled trial.. The Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) study, a randomized, double-blind, placebo-controlled trial that examined the effects of vitamin E, 50 mg/d, and beta-carotene, 20 mg/d, on lung cancer using a 2 x 2 factorial design. The trial was conducted in the general community in southwestern Finland in 1985 to 1993; the intervention lasted for 6.1 years (median). The hypothesis being tested in the present study was formulated after the trial was closed.. ATBC study cohort of 29,133 men aged 50 to 69 years, who smoked at least five cigarettes per day, at baseline.. The first occurrence of hospital-treated pneumonia was retrieved from the national hospital discharge register (898 cases).. Vitamin E supplementation had no overall effect on the incidence of pneumonia (relative risk [RR], 1.00; 95% confidence interval [CI], 0.88 to 1.14) nor had beta-carotene supplementation (RR, 0.98; 95% CI, 0.85 to 1.11). Nevertheless, the age of smoking initiation was a highly significant modifying factor. Among subjects who had initiated smoking at a later age (> or =21 years; n = 7,469 with 196 pneumonia cases), vitamin E supplementation decreased the risk of pneumonia (RR, 0.65; 95% CI, 0.49 to 0.86), whereas beta-carotene supplementation increased the risk (RR, 1.42; 95% CI, 1.07 to 1.89).. Data from this large controlled trial suggest that vitamin E and beta-carotene supplementation have no overall effect on the risk of hospital-treated pneumonia in older male smokers, but our subgroup finding that vitamin E seemed to benefit subjects who initiated smoking at a later age warrants further investigation.

Topics: Aged; beta Carotene; Community-Acquired Infections; Confidence Intervals; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Follow-Up Studies; Hospitalization; Humans; Lung Neoplasms; Male; Middle Aged; Pneumonia; Probability; Risk Assessment; Severity of Illness Index; Smoking; Treatment Outcome; Vitamin E

In many observational studies, a higher intake of individual antioxidants is inversely associated with lung cancer risk. Data from in vitro and animal experiments suggest that there are biochemical interactions among antioxidant nutrients; therefore, consideration of multiple antioxidants simultaneously may be important in terms of risk estimation. The authors constructed a dietary antioxidant index and evaluated its ability to predict lung cancer risk within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. At baseline (1985-1988), 27,111 Finnish male smokers aged 50-69 years completed a dietary questionnaire that assessed usual frequency of consumption and portion sizes for the previous 12 months. A total of 1,787 incident cases of lung cancer were identified during a follow-up period of up to 14.4 years (1985-1999). Principal components analyses were individually applied to the carotenoid, flavonoid, and vitamin E nutrient groups, and summation of retained principal component scores, plus selenium and vitamin C, yielded the composite antioxidant index. In multivariate proportional hazards models, the relative risks for lung cancer according to increasing quintiles of the antioxidant index were 1.00 (referent), 1.00 (95% confidence interval (CI): 0.87, 1.14), 0.91 (95% CI: 0.79, 1.05), 0.79 (95% CI: 0.68, 0.92), and 0.84 (95% CI: 0.72, 0.98) (p for trend = 0.002). These findings support the hypothesis that a combination of dietary antioxidants reduces lung cancer risk in male smokers.

Topics: Aged; alpha-Tocopherol; Antioxidants; beta Carotene; Cohort Studies; Diet; Double-Blind Method; Finland; Humans; Incidence; Life Style; Lung Neoplasms; Male; Middle Aged; Registries; Risk Factors; Smoking; Surveys and Questionnaires

The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the effect of daily beta-carotene (30 mg) and retinyl palmitate (25,000 IU) on the incidence of lung cancer, other cancers, and death in 18,314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure. CARET was stopped ahead of schedule in January 1996 because participants who were randomly assigned to receive the active intervention were found to have a 28% increase in incidence of lung cancer, a 17% increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group.. After the intervention ended, CARET participants returned the study vitamins to their study center and provided a final blood sample. They continue to be followed annually by telephone and mail self-report. Self-reported cancer endpoints were confirmed by review of pathology reports, and death endpoints were confirmed by review of death certificates. All statistical tests were two-sided.. With follow-up through December 31, 2001, the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 (95% confidence interval [CI] = 0.97 to 1.31) and 1.08 (95% CI = 0.99 to 1.17), respectively. Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up. By contrast, the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped. During the post-intervention phase, females had larger relative risks of lung cancer mortality (1.33 versus 1.14; P = .36), cardiovascular disease mortality (1.44 versus 0.93; P = .03), and all-cause mortality (1.37 versus 0.98; P = .001) than males.. The previously reported adverse effects of beta-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant. Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females, and cardiovascular disease mortality primarily to females and to former smokers.

Topics: Adult; Aged; Anticarcinogenic Agents; beta Carotene; Carcinogens; Cardiovascular Diseases; Confidence Intervals; Female; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Sex Factors; United States

Associations between lung cancer risk and common polymorphisms in the DNA repair genes xeroderma pigmentosum complementation group D (XPD), X-ray repair cross-complementing group 1 (XRCC1), XRCC3 and apurinic/apyrimidinic endonuclease/redox factor 1 were examined within a randomized clinical trial designed to determine whether alpha-tocopherol, beta-carotene, or both would reduce cancer incidence among male smokers in Finland. We found no direct association between lung cancer risk and any of the DNA repair genotypes studied, however, the association between XPD codon 751 genotype and lung cancer was modified by alpha-tocopherol supplementation, and the association between XRCC1 codon 399 genotype and lung cancer was modified by the amount of smoking. Our results suggest that common alterations in single DNA repair genes are not major determinants of lung cancer susceptibility among smokers.

Topics: Aged; alpha-Tocopherol; beta Carotene; Carbon-Oxygen Lyases; Case-Control Studies; DNA Helicases; DNA Repair; DNA-(Apurinic or Apyrimidinic Site) Lyase; DNA-Binding Proteins; DNA, Neoplasm; Finland; Humans; Lung Neoplasms; Male; Middle Aged; Polymorphism, Genetic; Prospective Studies; Proteins; Risk Factors; Smoking; Transcription Factors; X-ray Repair Cross Complementing Protein 1; Xeroderma Pigmentosum Group D Protein

Despite the unexpected results from the beta-Carotene and Retinol Efficacy Trial (CARET) and similar supplementation trials showing that supplementation with beta-carotene increased, rather than decreased, lung cancer incidence, considerable interest remains in investigating how other compounds in fruits and vegetables may affect lung cancer risk. We used data from 14,120 CARET participants who completed food frequency questionnaires to examine associations of diet with lung cancer risk. After 12 years of follow-up (1989-2001), 742 participants developed lung cancer. We used Cox proportional hazards models to estimate multivariate relative risks (RRs) and 95% confidence intervals (CIs). Analyses were controlled for smoking, asbestos exposure, and other covariates. Analyses of specific botanical groups were also controlled for total fruit and vegetable intake. All models were stratified by CARET treatment arm, and all statistical tests were two-sided. Statistically significant associations of fruit and vegetable intake with lower lung cancer risk were restricted to the CARET placebo arm. The RR for highest versus lowest quintile of total fruit consumption in the placebo arm was 0.56 (95% CI, 0.39-0.81) with a two-sided P for trend = 0.003. Two specific botanical groups were associated with reduced risk of lung cancer. Compared with the lowest quintile of rosaceae fruit consumption, placebo participants in the top quintile had a RR of 0.63 (95% CI, 0.42-0.94; P for trend = 0.02); for cruciferae vegetables, the RR was 0.68 (95% CI, 0.45-1.04; P for trend = 0.01). We did not observe any statistically significant associations of fruit and vegetable intake with lung cancer risk among participants randomized to receive the CARET supplements (30 mg of beta-carotene and 25,000 IU of retinyl palmitate). This report provides evidence that plant foods have an important preventive influence in a population at high risk for lung cancer. However, persons who use beta-carotene supplements do not benefit from the protective compounds in plant foods.

Topics: Aged; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Carcinoma, Small Cell; Double-Blind Method; Feeding Behavior; Female; Follow-Up Studies; Fruit; Humans; Lung Neoplasms; Male; Middle Aged; Placebos; Risk Factors; Statistics as Topic; Treatment Outcome; Vegetables; Vitamin A

beta-Carotene and Retinol Efficacy Trial is a nationwide chemoprevention trial that recruited 18,314 high-risk individuals to test the effect of supplemental beta-carotene and retinol on lung cancer incidence. In this report, we conducted a prospective nested case-control study of the association between serum carotenoids, retinoids, and tocopherols on both lung and prostate cancer incidence. Prerandomization serum samples were selected from 278 lung cancer cases and 205 prostate cancer cases, and 483 controls matched by high-risk population, study center location, age, sex (lung cancer only), smoking status, and year of randomization. Carotenoids, retinoids, and tocopherols were analyzed by high-performance liquid chromatography. Endpoints were confirmed by pathology review (lung cancer) or review of the pathology report (prostate cancer). In the control-only population, there was a significant association between tobacco use and serum micronutrient concentration. Current smokers compared with former smokers had lower mean levels of all of the micronutrients tested with zeaxanthin, beta-cryptoxanthin, alpha-carotene, alpha-tocopherol, retinol, and retinyl palmitate reaching statistical significance at P = 0.05. In the overall population, the mean serum concentrations of all of the micronutrients except gamma-tocopherol were lower for lung cancer cases than controls. Statistically significant trends across quartiles were observed in lutein (P = 0.02), zeaxanthin (P = 0.02), and alpha-tocopherol (P = 0.03). The carotenoid findings in the overall population were because of the strong inverse association between serum micronutrients and lung cancer in females. Statistically significant odds ratios (ORs) comparing 4(th) to 1st quartiles in the female population were seen in lutein [OR, 0.31; confidence interval (CI), 0.13-0.75], zeaxanthin (OR, 0.31; CI, 0.12-0.77), and beta-cryptoxanthin (OR, 0.34; CI, 0.14-0.81). For prostate cancer, mean serum concentrations were lower in cases for all of the nutrients except alpha-carotene. Only for alpha-tocopherol (P(trend) = 0.04) were the findings statistically significant. There was no statistically significant association between serum carotenoids and prostate cancer. Our findings provide additional support for the association between physiological levels of dietary micronutrients and cancer incidence.

Topics: Aged; alpha-Tocopherol; Antioxidants; beta Carotene; Biomarkers, Tumor; Carotenoids; Case-Control Studies; Double-Blind Method; Female; gamma-Tocopherol; Humans; Lung Neoplasms; Male; Micronutrients; Middle Aged; Prospective Studies; Prostatic Neoplasms; Risk Factors; Smoking; Statistics as Topic; Treatment Outcome; Vitamin A

DNA damage from polycyclic aromatic hydrocarbons (PAH) and other aromatic/hydrophobic compounds has been implicated in case-control studies as a risk factor for lung cancer, as have common polymorphisms in the glutathione S-transferase (GST) genes involved in carcinogen detoxification. However, their joint effects have not been evaluated in prospective studies, leaving open questions about predictive value of these biomarkers. In this matched case-control study nested within the prospective Physicians' Health Study, we evaluated whether biomarkers measured in white blood cells (WBC) significantly predicted risk, alone and in combination, after controlling for level of smoking. The biomarkers reported here are aromatic/hydrophobic-DNA adducts and polymorphisms in genes coding for the GSTM1 and GSTP1 enzymes. Our study population was composed of 89 cases of primary lung cancer and 173 controls, matched in a 1:2 ratio on smoking, age and duration of follow up. Adducts were measured in WBC DNA by the nuclease P1-enhanced (32)P-post-labeling method. Genotypes (GSTM1 null versus non-null and GSTP1 Val versus GSTP1 Ile) were determined by genomic amplification and restriction fragment length polymorphism analysis. Among current smokers, adducts were significant predictors of lung cancer risk (after adjusting for GST genotypes, OR = 3.10, 95% CI 1.07, 9.01). The combined GSTM1 null/GSTP1 Val genotype was associated with lung cancer overall and especially among former smokers, before and after adjusting for adducts (OR for former smokers = 4.21, CI 1.08, 16.41; adjusted OR = 4.68, CI 1.17, 18.71). Among cases only, adducts were significantly higher among current or former smokers with the GSTM1 non-null/GSTP1 Ile genotype. The two risk factors (adducts and genotypes) appear to be independent predictors of risk. The findings underscore the complex and important role of biological susceptibility as a determinant of risk from carcinogens found in tobacco smoke and other environmental compounds.

Topics: beta Carotene; Biomarkers; Carcinogens; Case-Control Studies; DNA Adducts; DNA Damage; Gene Deletion; Genotype; Glutathione Transferase; Humans; Isoenzymes; Leukocytes; Lung Neoplasms; Polymorphism, Genetic; Predictive Value of Tests; Risk Factors; Smoking

Recent prospective studies have suggested that insulin-like growth factor (IGF)-I levels are related to risk of some epithelial cancers. We previously reported in a case-control study a significant association between IGF-I level and lung cancer risk, with a 2-fold increased risk in the highest quartile. We now report the results of a lung cancer case-control study nested in the placebo arm of the beta-Carotene and Retinol Efficacy Trial in heavy smokers. We identified 159 cases for whom sera had been collected at least 3 years before diagnosis and for whom 2 suitable controls/case (final number, 297) could be matched from the same study arm on age (within 5-year intervals), sex, ethnicity, year of enrollment into the beta-Carotene and Retinol Efficacy Trial, year of blood draw, and exposure category (smoking or asbestos). The cases were significantly heavier smokers than the controls (mean pack-years, 58.7 and 45.9, respectively; P < 0.001). An inverse relationship between IGF-I level and age was evident only for former smokers, and not for those who were current smokers at the time of blood draw. Both IGF-I and IGF-binding protein (IGFBP)-3 levels were higher in cases than in controls, but none of the differences achieved statistical significance. The odds ratios for IGF-I were around unity, except for subsets of heaviest smokers and those who had quit smoking for the longest period of time, in whom there were elevated risks in the second to fourth quartiles of IGF-I relative to the first quartile (odds ratios, 2.21-2.91), although again, none achieved statistical significance. For younger subjects, IGF-I was inversely associated with lung cancer risk in the models that also controlled for IGFBP-3. Elevated risks for lung cancer were noted in the highest quartile of IGFBP-3 level, and these tended to be higher in current smokers and more recent quitters. These results do not support the conclusions of our prior case-control study. It is possible that current smoking or recent cessation may exert a suppressive effect on IGF-I levels (notably in younger subjects with higher baseline levels) that may obscure a relatively modest association between IGF-I level and lung cancer risk. On the other hand, risks associated with elevated IGFBP-3 level tended to be higher in current smokers and more recent quitters. This trend toward a positive association with IGFBP-3 level is unexpected and requires further investigation. Finally, from these data, we cannot exclu

Topics: Aged; Antioxidants; beta Carotene; Biomarkers, Tumor; Case-Control Studies; Double-Blind Method; Female; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Lung Neoplasms; Male; Middle Aged; Odds Ratio; Prevalence; Risk Factors; Smoking; Statistics as Topic; Treatment Outcome; United States; Vitamin A

To study the associations between the intake of flavonols and flavones and the risk of cancer.. The study cohort consisted of 27,110 male smokers, aged 50-69 years, without history of cancer. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire at baseline. Incident cases of cancers were identified through national registers. During an average 6.1-year follow-up, 791 lung cancers, 226 prostate cancers, 156 urothelial cancers, 133 colorectal cancers, 111 stomach cancers, and 92 renal cell cancers were diagnosed.. Intake of flavonols and flavones was inversely associated with the risk of lung cancer; multivariate relative risk in the highest vs. the lowest quartile 0.56, 95% confidence interval 0.45-0.69, p for trend 0.0001. The risk was similar in all histological types of lung cancer. No association was found between flavonol and flavone intake and the risk of other cancers.. Intake of flavonols and flavones seemed to be inversely associated with the risk of lung cancer, but not with that of other cancers.

Topics: Aged; alpha-Tocopherol; Anticarcinogenic Agents; Antioxidants; beta Carotene; Diet; Double-Blind Method; Finland; Flavonoids; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Proportional Hazards Models; Registries; Risk; Smoking

The Physicians' Health Study (PHS) was a randomized trial of beta-carotene (50 mg, alternate days) and aspirin in primary prevention of cancer and cardiovascular disease among 22,071 US male physicians. This report updates results for beta-carotene and examines effect modification by baseline characteristics.. Beta-carotene's effect on cancer over nearly 13 years was examined overall and within subgroups defined by baseline characteristics using proportional-hazards models.. 2667 incident cancers were confirmed, with 1117 prostate, 267 colon, and 178 lung cancers. There were no significant differences with supplementation in total (relative risk (RR) = 1.0, 95% confidence interval (CI) = 0.9-1.0); prostate (RR = 1.0, 95% CI = 0.9-1.1); colon (RR = 0.9, 95% CI = 0.7-1.2); or lung (RR = 0.9, 95% CI = 0.7-1.2) cancer, and no differences over time. In subgroup analyses, total cancer was modestly reduced with supplementation among those aged 70+ years (RR = 0.8, 95% CI = 0.7-1.0), daily drinkers of alcohol (RR = 0.9, 95% CI = 0.8-1.0), and those in the highest BMI quartile (RR = 0.9, 95% CI = 0.7-1.0). Prostate cancer was reduced with supplementation among those in the highest BMI quartile (RR = 0.8, 95% CI = 0.6-1.0), and colon cancer was reduced among daily drinkers of alcohol (RR = 0.5, 95% CI = 0.3-0.8).. The PHS found no overall effect of beta-carotene on total cancer, or the three most common site-specific cancers. The possibility of risk reduction within specific subgroups remains.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; beta Carotene; Body Mass Index; Cardiovascular Diseases; Colonic Neoplasms; Double-Blind Method; Humans; Incidence; Life Style; Lung Neoplasms; Male; Middle Aged; Neoplasms; Physicians; Prostatic Neoplasms; Risk Factors; United States

The validity of stroke diagnosis in the National Hospital Discharge Register and the Register of Causes of Death was examined among 546 middle-aged men in Finland. The subjects were cases of cerebrovascular diseases of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and identified by record linkage to the registers. In all, 375 events with cerebrovascular disease as hospital discharge diagnosis and 218 events with cerebrovascular disease as the underlying cause of death were reviewed using specific criteria modified from the classifications of the National Survey of Stroke and the WHO MONICA Study. For hospital stroke diagnoses, there was agreement on diagnosis for all strokes in 90%, for subarachnoid hemorrhage in 79%, intracerebral hemorrhage in 82%, and cerebral infarction in 90%. The respective agreement rates for stroke as the underlying cause of death were 97%, 95%, 91%, and 92%. The data were insufficient for review in 1% and 3% of the stroke events, respectively. Age, observation year and trial supplementation with alphatocopherol or beta-carotene had no effect on validity. In conclusion, the validity of stroke diagnosis was good in registers of hospital diagnoses and causes of death justifying their use for endpoint assessment in epidemiological studies.

Topics: Age Factors; Aged; beta Carotene; Cause of Death; Cerebral Hemorrhage; Cerebral Infarction; Cerebrovascular Disorders; Classification; Double-Blind Method; Finland; Humans; Lung Neoplasms; Male; Medical Record Linkage; Middle Aged; Patient Discharge; Placebos; Registries; Reproducibility of Results; Smoking; Subarachnoid Hemorrhage; Vitamin E

The Carotene and Retinol Efficacy Lung Cancer Chemoprevention Trial (CARET) ended prematurely due to the unexpected findings that the active treatment group on the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate had a 46% increased lung cancer mortality and a 26% increased cardiovascular mortality compared with placebo. This study was designed when the CARET intervention was halted to evaluate the effects of long-term supplementation with beta-carotene and retinol on serum triglyceride and cholesterol levels, in an attempt to explore possible explanations for the CARET result.. Serum triglyceride levels, and total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels were determined in a subgroup of 52 CARET participants. Baseline and mid-trial levels were available on 23 participants on placebo and 29 on active treatment who were then serially followed for 10 months after trial termination.. Triglyceride, and total, HDL and LDL cholesterol levels were similar in the two groups at baseline. After a mean of 5 years on the intervention there was a small nonsignificant increase in serum triglyceride levels in the active group, but no difference in total, HDL, or LDL cholesterol levels. After stopping the intervention there was a decrease in triglyceride levels in the active intervention group, and no change in the other parameters.. Based on a small convenience sample, CARET participants in the active treatment arm had a small nonsignificant increase in serum triglyceride levels while on the intervention, and a decrease in serum triglyceride levels after the intervention was discontinued. No significant changes in total or HDL cholesterol were noted. These results argue against a major contribution of treatment-induced changes in serum lipid and lipoprotein levels to the increased cardiovascular mortality in the active treatment group.

Topics: beta Carotene; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Chromatography, High Pressure Liquid; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Survival Rate; Treatment Outcome; Triglycerides; Vitamin A

Higher blood levels of alpha-tocopherol, the predominant form of vitamin E, have been associated in some studies with a reduced risk of lung cancer, but other studies have yielded conflicting results. To clarify this association, we examined the relationship between prospectively collected serum alpha-tocopherol and lung cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort.. The ATBC Study was a randomized, clinical trial of 29 133 white male smokers from Finland who were 50-69 years old and who had received alpha-tocopherol (50 mg), beta-carotene (20 mg), both, or neither daily for 5-8 years. Data regarding medical histories, smoking, and dietary factors were obtained at study entry, as was a serum specimen for baseline alpha-tocopherol determination. alpha-Tocopherol measurements were available for 29 102 of the men, among whom 1144 incident cases of lung cancer were diagnosed during a median observation period of 7.7 years. The association between alpha-tocopherol and lung cancer was evaluated with the use of multivariate proportional hazards regression.. A 19% reduction in lung cancer incidence was observed in the highest versus lowest quintile of serum alpha-tocopherol (relative risk = 0.81; 95% confidence interval = 0. 67-0.97). There was a stronger inverse association among younger men (<60 years), among men with less cumulative tobacco exposure (<40 years of smoking), and possibly among men receiving alpha-tocopherol supplementation.. In the ATBC Study cohort, higher serum alpha-tocopherol status is associated with lower lung cancer risk; this relationship appears stronger among younger persons and among those with less cumulative smoke exposure. These findings suggest that high levels of alpha-tocopherol, if present during the early critical stages of tumorigenesis, may inhibit lung cancer development.

Topics: Adenocarcinoma; Aged; beta Carotene; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Dietary Supplements; Finland; Humans; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Risk; Risk Factors; Smoking; Treatment Outcome; Vitamin E

The Physicians' Health Study was a randomized, double-blind, placebo-controlled trial using a 2x2 factorial design including supplementation with beta-carotene (50 mg every other day) in the primary prevention of cancer among 22,071 U.S. male physicians ages 40-84 years at randomization. Before randomization, the authors collected baseline blood specimens to determine whether any benefit was greater among or confined to those with low baseline levels of beta-carotene.. Baseline blood samples were collected from 14,916 participants. These samples were assayed, according to a nested case-control design, from 1439 men subsequently diagnosed with cancer over 12 years of follow-up (631 with prostate carcinoma) and 2204 controls matched by age and smoking habits.. Men in the lowest quartile for plasma beta-carotene at baseline had a marginally significant (P = 0.07) increased risk of cancer compared with those in the highest quartile (relative risk [RR] = 1.30, 95% confidence interval [CI], 0.98-1.74). Men in the lowest quartile assigned at random to beta-carotene supplementation had a possible but nonsignificant decrease in overall cancer risk (RR = 0.83, 95% CI, 0.63-1.09) compared with those assigned to placebo. This was primarily due to a significant reduction in the risk of prostate carcinoma (RR = 0.68, 95% CI, 0. 46-0.99) in this group. After the first 2 years of follow-up were excluded, the results were virtually unchanged.. These prespecified subgroup analyses appeared to support the idea that beta-carotene supplementation may reduce risk of prostate carcinoma among those with low baseline levels. Further follow-up of this population will help determine whether these findings are valid.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Case-Control Studies; Colonic Neoplasms; Dietary Supplements; Double-Blind Method; Epidemiologic Studies; Follow-Up Studies; Humans; Lung Neoplasms; Lymphoma; Male; Melanoma; Middle Aged; Prostatic Neoplasms; Risk; Smoking

The GSTM1 (glutathione S-transferase mu-1) null genotype is suspected of increasing an individual's susceptibility to tobacco smoke carcinogens because of impaired carcinogen detoxification. We were interested in whether there were differences in lung cancer susceptibility to smoking within the GSTM1 genotypes and the impact of antioxidant supplementation on this. For this purpose, we conducted a nested lung cancer case-control study and evaluated the role of GSTM1 within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. GSTM1 genotype status was determined for 319 cases and 333 controls using a PCR-based approach. GSTM1 was evaluated as an independent risk factor and as an effect modifier of smoking using logistic regression analyses. The GSTM1 null genotype itself was unrelated to risk of lung cancer, odds ratio (OR) = 1.09 and 95% confidence interval (CI), 0.79-1.50, but it may have modified the effect of smoking. There was a suggestion for a stronger association between years of smoking and lung cancer among the GSTM1 null genotype, but the differences between GSTM1 null and present genotypes were not statistically significant (P = 0.12). Furthermore, the smoking association was strongest among those with the GSTM1 null genotype not receiving alpha-tocopherol supplementation, whereas among those receiving alpha-tocopherol, there was no modification by GSTM1 on the association between smoking duration and lung cancer risk. Beta-carotene supplementation did not modify the relationship between GSTM1, smoking years, and lung cancer risk. In conclusion, GSTM1 is not associated with lung cancer risk in male smokers but may confer a higher susceptibility to cumulative tobacco exposure. This association may be attenuated by alpha-tocopherol but not by beta-carotene supplementation.

Topics: Adult; Age Distribution; Aged; Antioxidants; beta Carotene; Case-Control Studies; Cohort Studies; Confidence Intervals; Finland; Genotype; Glutathione Transferase; Humans; Incidence; Logistic Models; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Polymerase Chain Reaction; Risk Factors; Sampling Studies; Smoking; Vitamin E

In the alpha-Tocopherol, beta-Carotene Cancer Prevention (ATBC) study, a large randomized placebo-controlled trial designed to test the cancer prevention effects of alpha-tocopherol (50 mg/day) and beta-carotene (20 mg/day), participants receiving supplemental beta-carotene had significantly higher rates of lung cancer than those not receiving beta-carotene. It has been hypothesized that the supplemental beta-carotene may have interfered with the synthesis of vitamin D and that the resulting lower concentrations of vitamin D contributed to the elevated cancer incidence. We evaluated whether supplementation with beta-carotene altered the serum concentrations of either 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D in the ATBC Study, by comparing on-study changes between baseline and follow-up serum samples among 20 randomly selected matched pairs of subjects from the beta-carotene and placebo groups. In a matched-pair analysis, the difference between the changes in both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in the beta-carotene supplement and placebo groups were small and statistically nonsignificant. These results provide no evidence that beta-carotene supplementation interferes with the endogenous production of 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D and suggest that it is unlikely that an interaction between supplemental beta-carotene and vitamin D metabolites contributed to the modest increase in lung cancer incidence observed in the ATBC Study.

Topics: Age Factors; Antioxidants; beta Carotene; Drug Interactions; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Matched-Pair Analysis; Placebos; Seasons; Statistics, Nonparametric; Time Factors; Vitamin D

Former blue asbestos workers known to be at high risk of asbestos-related diseases, particularly malignant mesothelioma and lung cancer, were enrolled in a chemo-prevention program using vitamin A. Our aims were to compare rates of disease and death in subjects randomly assigned to beta-carotene or retinol. Subjects were assigned randomly to take 30 mg/day beta-carotene (512 subjects) or 25,000 IU/day retinol (512 subjects) and followed up through death and cancer registries from the start of the study in June 1990 till May 1995. Comparison between groups was by Cox regression in both intention-to-treat analyses and efficacy analyses based on treatment actually taken. Median follow-up time was 232 weeks. Four cases of lung cancer and 3 cases of mesothelioma were observed in subjects randomised to retinol and 6 cases of lung cancer and 12 cases of mesothelioma in subjects randomised to beta-carotene. The relative rate of mesothelioma (the most common single cause of death in our study) for those on retinol compared with those on beta-carotene was 0.24 (95% CI 0.07-0.86). In the retinol group, there was also a significantly lower rate for death from all causes but a higher rate of ischaemic heart disease mortality. Similar results were found with efficacy analyses. Our results confirm other findings of a lack of any benefit from administration of large doses of synthetic beta-carotene. The finding of significantly lower rates of mesothelioma among subjects assigned to retinol requires further investigation.

Topics: Adult; Aged; Aged, 80 and over; Anticarcinogenic Agents; Asbestos, Crocidolite; beta Carotene; Female; Humans; Incidence; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Myocardial Ischemia; Occupational Exposure; Patient Compliance; Risk Factors; Smoking; Vitamin A

The Carotene and Retinol Efficacy Trial (CARET), a randomized, placebo-controlled lung cancer chemoprevention trial of 30 mg of beta-carotene and 25,000 IU of retinyl palmitate, was prematurely terminated when a 46% excess lung cancer mortality was found in subjects on the active arm. Before the CARET intervention ended, 21 men were recruited to participate in a 6-month biomarker study using the same intervention as CARET that determined the effect of this supplementation on lung nutrient levels. Plasma and bronchoalveolar lavage (BAL) cell nutrient levels were measured before and after the intervention. The group in the active arm (n = 10) had plasma carotene level increases of over 10-fold, with a small increase in plasma retinol levels BAL cell levels of beta-carotene in the active group also increased 10-fold, from 4.5 to 46.3 pmol/10(6) cells (P = 0.0008), with no change in BAL cell retinol levels. Surgically obtained lung tissue from three CARET subjects in the active arm showed elevated carotene lung tissue levels but no increase in lung retinol levels compared to a group of surgical controls. Combined with our previous work showing a strong correlation between BAL and lung tissue nutrient levels, these findings suggest that supplementation with beta-carotene and vitamin A results in increased lung tissue as well as BAL cell levels of beta-carotene, with little change in lung retinol.

Topics: Aged; Anticarcinogenic Agents; Asbestosis; beta Carotene; Bronchoalveolar Lavage Fluid; Bronchoscopy; Carotenoids; Diterpenes; Double-Blind Method; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Retinyl Esters; Risk Factors; Smoking; Vitamin A

Animal research and observational studies in man suggest a protective effect of antioxidant vitamins in the development of age-related maculopathy (ARM).. The ATBC study, a population-based, controlled clinical trial of alpha-tocopherol and beta carotene to prevent lung cancer, took place in Finland between 1984 and 1993. Over 29,000 smoking males aged 50 to 69 years were randomly assigned to alpha-tocopherol (AT; 50 mg/day), beta-carotene (BC; 20 mg/day), both of these, or placebo. We performed an end-of-trial ophthalmological examination on a random sample of 941 participants aged 65 years or more from two of the fourteen study areas, to discover if the five to eight-year intervention with alpha-tocopherol and/or beta-carotene had been associated with a difference in ARM prevalence. Age-related maculopathy was assessed using colour photographs of the macula.. Altogether, 269 cases of ARM were found; there were more cases in the AT group (32%; 75/237), BC group (29%; 68/234), and combined antioxidant group (28%; 73/257) than in the placebo group (25%; 53/213). However, neither substance was significantly associated with the risk of ARM in a logistic regression analysis controlling for possible risk factors.. No beneficial effect of long-term supplementation with alpha-tocopherol or beta-carotene on the occurrence of ARM was detected among smoking males.

Topics: Aged; Aging; Antioxidants; beta Carotene; Double-Blind Method; Finland; Humans; Lung Neoplasms; Macula Lutea; Male; Prevalence; Retinal Diseases; Vitamin E

The Beta-Carotene and Retinol Efficacy Trial tested the effect of the combination of beta-carotene (30 mg) and retinyl palmitate (25,000 units) daily on the incidence of lung cancer in high-risk individuals. In study centers located in Seattle, WA; Portland, OR; and Irvine, CA, we recruited current and recent ex-cigarette smokers, aged 50-69 years. Our primary method of recruitment was by mailing study information and eligibility questionnaires to age-selected health insurance subscribers. A total of 1,216,549 subscriber households were contacted, which resulted in 16,449 enrollments and 12,184 randomizations. Other methods of recruitment yielded 1421 enrollments and 1002 randomizations. Seventy-four % of those participants who enrolled in the 3-month placebo run-in were randomized. The major reasons for nonrandomization once subjects were enrolled were: becoming ineligible (13%), concern about or development of side effects attributed to the study vitamins (18%), loss of interest or being too busy (23%), and not showing up at the appointed time or not willing to come to the study center (23%). Here, we discuss the reasons for nonparticipation and for subjects leaving the trial prior to randomization and possible modifications of trial design and procedures to address these problems. This recruitment approach provided a constant flow of potentially eligible participants, screened out many ineligible and uninterested persons prior to the scheduling of a study center visit, and ensured randomization of committed participants. A major limitation of this study was that the pool of minorities that was reached was small.

Topics: Aged; beta Carotene; California; Female; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Oregon; Patient Selection; Pilot Projects; Random Allocation; Smoking; Vitamin A; Washington

Alpha-tocopherol (vitamin E) may play a role in the treatment of arterial thromboembolic disease, possibly by inhibiting platelet aggregation. Thus far, no clinical evidence exists for this effect. The objective of this study was to assess the effect of alpha-tocopherol supplementation on gingival bleeding either in combination with acetylsalicylic acid (ASA) or without it. This study was an end-point examination of a random sample of male smokers who had participated in a controlled clinical trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) for 5-7 years. The study included 409 men aged 55-74 years of whom 191 received alpha-tocopherol supplementation (50 mg/day); 56 used ASA, 30 received both and 132 received neither. Gingival bleeding was examined by probing with a WHO probe and reported as a percentage of bleeding sites adjusted by the logistic regression model. Gingival bleeding was more common in those who received alpha-tocopherol compared with nonreceivers among subjects with a high prevalence of dental plaque (P < 0.05). ASA alone increased bleeding only slightly. The highest risk of gingival bleeding was among those who took both alpha-tocopherol and ASA (33.4% of probed sites bleeding vs 25.8% among subjects taking neither alpha-tocopherol nor ASA, P < 0.001). In the ATBC Study, more deaths from haemorrhagic stroke and fewer from ischaemic heart disease were observed among those participants who received alpha-tocopherol compared with those who did not. Based on the results of the present study and the ATBC Study, we conclude that alpha-tocopherol supplementation may increase the risk of clinically important bleedings, particularly when combined with ASA.

Topics: Aged; Aspirin; beta Carotene; Humans; Lung Neoplasms; Male; Middle Aged; Periodontal Index; Platelet Aggregation Inhibitors; Random Allocation; Vitamin E

Epidemiological evidence suggests that airway obstruction is an independent risk factor for lung cancer and that this cannot be explained by active or passive smoking alone. Chlamydia pneumoniae infection has been associated with chronic bronchitis and its exacerbates. Our aim was to evaluate the association between chronic C. pneumoniae infection and risk of lung cancer among male smokers. Smoking males with lung cancer (n = 230) and their age- and locality-matched controls were selected among participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The presence of C. pneumoniae infection was assessed by analyzing specific antibodies and immune complexes in 2 serum samples collected with a 3-year interval before the lung cancer diagnosis. The diagnosis of chronic infection was based on stable levels of positive specific IgA antibody (titer > or = 16) and immune complex (titer > or = 4). Relative risks were estimated by odds ratios (OR) adjusted for age, locality and smoking history by a conditional logistic regression model. Markers suggesting chronic C. pneumoniae infection were present in 52% of cases and 45% of controls and hence were positively associated with the incidence of lung cancer (OR 1.6; 95% confidence interval [CI] 1.0-2.3). The incidence was especially increased in men younger than 60 years (OR 2.9; 95% CI 1.5-5.4) but not in the older age group (OR 0.9; 95% CI 0.5-1.6). Before concluding that C. pneumoniae infection is a new independent risk factor for lung cancer, corroboration from other studies with larger number of cases and longer follow-up is needed.

Topics: Age Factors; Aged; Antibodies, Bacterial; Anticarcinogenic Agents; beta Carotene; Chlamydia Infections; Chlamydophila pneumoniae; Cohort Studies; Double-Blind Method; Humans; Immunoglobulin A; Immunoglobulin G; Lung Neoplasms; Male; Middle Aged; Risk Factors; Smoking

The use of biomarkers is a promising approach to the study of human cancer risk. Bronchial metaplasia in sputum cytology may be a marker for potential premalignancy that can be used for population studies. We recently performed a randomized, controlled trial in smokers on the effect of 14 weeks beta-carotene (20mg/day) on markers for DNA damage. We now have evaluated the application of sputum cytology in this study and performed a preliminary evaluation of the effect of beta-carotene. Of the 150 potential participants in this trial 75 were not eligible because they failed to produce sputum samples (n = 29), or because samples were unsatisfactory (n = 46). The eligible group was older (41 vs 37 years) and had smoked longer (23 vs 19 years), but had similar cigarette consumption (mean 21/day) and plasma cotinine levels. Metaplasia was graded in seven categories. Only 11 subjects (15%) showed minor or mild atypia on study entry. Agreement within and between observers was 95% within the same or an adjacent category. We observed no significant correlation between before and after treatment final metaplasia scores in either the beta-carotene (Spearman R = 0.18, P = 0.3) or placebo group (Spearman R = 0.17, P = 0.3). Initial metaplasia scores were somewhat higher in the beta-carotene group (n = 33) than in the placebo group (n = 42) (P = 0.06). Final metaplasia scores were similar in both groups (P = 0.69), and there was no decrease in metaplasia scores in the beta-carotene group (P = 0.75). This study indicates that sputum cytology may not yet be a readily applicable marker in studies of a healthy asymptomatic population, because many smokers do not spontaneously produce sputum, more severe lesions are rare, and variation over time in the minor lesions in large. Therefore, the preliminary evidence that beta-carotene has no influence should be interpreted with care.

Topics: Adult; beta Carotene; Biomarkers; DNA Damage; Double-Blind Method; Humans; Lung Neoplasms; Male; Metaplasia; Middle Aged; Smoking; Sputum; Statistics, Nonparametric

To study if long-term supplementation with alpha-tocopherol or beta-carotene is associated with cataract prevalence and severity.. An end-of-trial random sample of 1828 participants from the randomized, double-blind, placebo-controlled clinical trial the alpha-tocopherol, beta-carotene cancer prevention study. The alpha-tocopherol, beta-carotene cancer prevention study was originally designed to examine whether supplementation with alpha-tocopherol or beta-carotene would reduce the incidence of lung cancer in male smokers. The participants for this study lived in Helsinki City or Uusimaa province and were at entry to the alpha-tocopherol, beta-carotene cancer prevention study 50 to 69 years old and smoked at least 5 cigarettes per day. They received alpha-tocopherol 50 mg/day, beta-carotene 20 mg/day, a combination of the two, or placebo supplements for 5 to 8 years (median 6.6 years). Outcome measures were: cortical, nuclear, and posterior subcapsular cataract, differentiated and quantified with lens opacity classification system (LOCS II). Lens opacity meter provided a continuous measure of cataract density.. Supplementation with alpha-tocopherol or beta-carotene was not associated with the end-of-trial prevalence of nuclear (odds ratio 1.1 and 1.2, respectively), cortical (odds ratio 1.0 and 1.3, respectively), or posterior subcapsular cataract (odds ratio 1.1 and 1.0, respectively) when adjusted for possible confounders in logistic model. Neither did the median lens opacity meter values differ between the supplementation groups, indicating no effect of alpha-tocopherol or beta-carotene on cataract severity.. Supplementation with alpha-tocopherol or beta-carotene for 5 to 8 years does not influence the cataract prevalence among middle-aged, smoking men.

Topics: Aged; Aging; Antioxidants; beta Carotene; Cataract; Double-Blind Method; Drug Therapy, Combination; Finland; Follow-Up Studies; Humans; Lens, Crystalline; Lung Neoplasms; Male; Middle Aged; Prevalence; Risk Factors; Vitamin E

Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders.. We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo.. A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years.. After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.

Topics: Aged; Antioxidants; Asbestos; beta Carotene; Cardiovascular Diseases; Carotenoids; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Mortality; Occupational Exposure; Risk; Smoking; Vitamin A

Evidence has accumulated from observational studies that people eating more fruits and vegetables, which are rich in beta-carotene (a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver) and retinol (an alcohol chemical form of vitamin A), and people having higher serum beta-carotene concentrations had lower rates of lung cancer. The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate (vitamin A) taken daily against placebo in 18314 men and women at high risk of developing lung cancer. The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm; there were 28% more lung cancers and 17% more deaths in the active intervention group (active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate). Promptly after the January 18, 1996, announcement that the CARET active intervention had been stopped, we published preliminary findings from CARET regarding cancer, heart disease, and total mortality.. We present for the first time results based on the pre-specified analytic method, details about risk factors for lung cancer, and analyses of subgroups and of factors that possibly influence response to the intervention.. CARET was a randomized, double-blinded, placebo-controlled chemoprevention trial, initiated with a pilot phase and then expanded 10-fold at six study centers. Cigarette smoking history and status and alcohol intake were assessed through participant self-report. Serum was collected from the participants at base line and periodically after randomization and was analyzed for beta-carotene concentration. An Endpoints Review Committee evaluated endpoint reports, including pathologic review of tissue specimens. The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence, with weighting linearly to hypothesized full effect at 24 months after randomization. Relative risks (RRs) were estimated by use of Cox regression models; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake. O'Brien-Fleming boundaries were used for stopping criteria at interim analyses. Statistical significance was set at the .05 alpha value, and all P values were derived from two-sided statistical tests.. According to CARET's pre-specified analysis, there was an RR of 1.36 (95% confidence interval [CI] = 1.07-1.73; P = .01) for weighted lung cancer incidence for the active intervention group compared with the placebo group, and RR = 1.59 (95% CI = 1.13-2.23; P = .01) for weighted lung cancer mortality. All subgroups, except former smokers, had a point estimate of RR of 1.10 or greater for lung cancer. There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake (RR = 1.99; 95% CI = 1.28-3.09; test for heterogeneity of RR among quartiles of alcohol intake has P = .01, unadjusted for multiple comparisons) and with large-cell histology (RR = 1.89; 95% CI = 1.09-3.26; test for heterogeneity among histologic categories has P = .35), but not with base-line serum beta-carotene concentrations.. CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality. The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finland.

Topics: Anticarcinogenic Agents; Antioxidants; Asbestos; beta Carotene; Carcinogens; Diterpenes; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Proportional Hazards Models; Retinyl Esters; Risk Factors; Smoking; Vitamin A

Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and vitamin A.. We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations.. A total of 29,133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests.. No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (> or = 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24).. Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke. beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake.. While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation.

Topics: Age Factors; Aged; Alcohol Drinking; Anticarcinogenic Agents; Antioxidants; beta Carotene; Carcinogens; Food, Fortified; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Patient Compliance; Proportional Hazards Models; Risk; Risk Factors; Smoking; Vitamin E

A randomized, placebo-controlled clinical trial of beta-carotene and retinol was conducted with 755 former asbestos workers as study subjects. The targeted endpoint for the intervention study was a reduction in the incidence and prevalence of sputum atypia. The dosage of 50 mg beta-carotene/d and 25,000 IU retinol/d on alternate days resulted significant increases in serum concentrations of both agents with no clinically significant toxicity. Skin yellowing was observed in approximately 35% of patients and may have contributed adversely to protocol adherence. Baseline analysis revealed that smoking and drinking were associated with lower concentrations of serum beta-carotene, even after dietary carotene intake was adjusted for (P < 0.0001). Baseline concentrations of retinol were apparently lowered by smoking (P < 0.002) and increased by drinking (P < 0.0001). Drinking and smoking also were significantly related to lower beta-carotene concentrations after supplementation (P < 0.001). No significant reduction in sputum atypia was observed after treatment.

Topics: Adult; Aged; Antioxidants; beta Carotene; Carotenoids; Double-Blind Method; Female; Humans; Lung Neoplasms; Male; Middle Aged; Vitamin A

Topics: Antioxidants; beta Carotene; Carotenoids; Coronary Disease; Humans; Lung Neoplasms; Male; Prostatic Neoplasms; Vitamin E

Topics: Aged; beta Carotene; Carotenoids; Drug Combinations; Finland; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Reproducibility of Results; Smoking; Treatment Outcome; Vitamin E

The U.S. National Cancer Institute and the Finnish National Public Institute jointly sponsored a large double-blind, placebo-controlled primary-prevention trial to examine the effects of vitamin E and beta-carotene supplementation on reducing the incidence of lung cancers in male smokers, ages 50-69 years. Supplementation did not result in a significant reduction in lung cancer, and a higher incidence of lung cancer was observed in the group receiving beta-carotene. These results should be examined within the context of the population studied before they are cited as definitive.

Topics: Aged; beta Carotene; Carotenoids; Cohort Studies; Double-Blind Method; Finland; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Registries; Smoking; Vitamin E

Epidemiologic evidence indicates that diets high in carotenoid-rich fruits and vegetables, as well as high serum levels of vitamin E (alpha-tocopherol) and beta carotene, are associated with a reduced risk of lung cancer.. We performed a randomized, double-blind, placebo-controlled primary-prevention trial to determine whether daily supplementation with alpha-tocopherol, beta carotene, or both would reduce the incidence of lung cancer and other cancers. A total of 29,133 male smokers 50 to 69 years of age from southwestern Finland were randomly assigned to one of four regimens: alpha-tocopherol (50 mg per day) alone, beta carotene (20 mg per day) alone, both alpha-tocopherol and beta carotene, or placebo. Follow-up continued for five to eight years.. Among the 876 new cases of lung cancer diagnosed during the trial, no reduction in incidence was observed among the men who received alpha-tocopherol (change in incidence as compared with those who did not, -2 percent; 95 percent confidence interval, -14 to 12 percent). Unexpectedly, we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not (change in incidence, 18 percent; 95 percent confidence interval, 3 to 36 percent). We found no evidence of an interaction between alpha-tocopherol and beta carotene with respect to the incidence of lung cancer. Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol than among those who did not. Beta carotene had little or no effect on the incidence of cancer other than lung cancer. Alpha-tocopherol had no apparent effect on total mortality, although more deaths from hemorrhagic stroke were observed among the men who received this supplement than among those who did not. Total mortality was 8 percent higher (95 percent confidence interval, 1 to 16 percent) among the participants who received beta carotene than among those who did not, primarily because there were more deaths from lung cancer and ischemic heart disease.. We found no reduction in the incidence of lung cancer among male smokers after five to eight years of dietary supplementation with alpha-tocopherol or beta carotene. In fact, this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects.

Topics: Aged; beta Carotene; Carotenoids; Cause of Death; Double-Blind Method; Finland; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Smoking; Vitamin E

CARET is a multicenter, two-armed, double-masked randomized chemoprevention trial in Seattle, Portland, San Francisco, Baltimore, Connecticut, and Irvine, to test whether oral administration of beta-carotene (30 mg/day) plus retinyl palmitate (25,000 IU/day) can decrease the incidence of lung cancer in high risk populations, namely, heavy smokers and asbestos-exposed workers. The intervention combines the antioxidant action of beta-carotene and the tumor suppressor mechanism of vitamin A. As of April 30, 1993, CARET had randomized 1,845 participants in the 1985-1988 pilot phase plus 13,260 "efficacy" participants since 1989; of these, 4,000 are asbestos-exposed males and 11,105 are smokers and former smokers (44% female). Accrual is complete everywhere except Irvine, which was the last center added (1991), and the safety profile of the regimen to date has been excellent. With 14,420 smokers, 4,010 asbestos-exposed participants, and 114,100 person-years through February 1998, we expect CARET to be capable of detecting a 23% reduction in lung cancer incidence in the two populations combined and 27, 49, 32, and 35% reductions in the smokers, female smokers, male smokers, and asbestos-exposed subgroups, respectively. CARET is highly complementary to the alpha-tocopherol-beta-carotene study in Finland and the Harvard Physicians Health Study (beta-carotene alone) in the National Cancer Institute portfolio of major cancer chemoprevention trials.

Topics: Aged; Anticarcinogenic Agents; Asbestos; beta Carotene; Carotenoids; Diterpenes; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Occupational Exposure; Pilot Projects; Retinyl Esters; Risk Factors; Smoking; United States; Vitamin A

The Alpha-Tocopherol, Beta-Carotene (ATBC) Lung Cancer Prevention Study was a randomized, double-blind, placebo-controlled, 2 x 2 factorial design, primary prevention trial testing the hypothesis that alpha-tocopherol (50 mg/day) and beta-carotene (20 mg/day) supplements reduce the incidence of lung cancer and possibly other cancers. Total and disease-specific mortality and incidence of various diseases and symptoms were monitored for safety. Between 1985 and 1993, 29,133 eligible male smokers aged 50 to 69 years at entry were randomized to receive daily active supplements or placebo capsules for 5 to 8 years (median 6.1 years), accumulating 169,751 follow-up years. This report describes the study design, methods, and protocol as well as the baseline characteristics and capsule compliance of the participants. The ATBC Study is the largest lung cancer chemoprevention trial conducted to date.

Topics: Adjuvants, Immunologic; Aged; beta Carotene; Carotenoids; Clinical Protocols; Double-Blind Method; Drug Monitoring; Drug Therapy, Combination; Finland; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Patient Compliance; Population Surveillance; Primary Prevention; Research Design; Risk Factors; Smoking; Vitamin E

Topics: beta Carotene; Carotenoids; Drug Therapy, Combination; Humans; Lung Neoplasms; Primary Prevention; Randomized Controlled Trials as Topic; Vitamin E

CARET is a chemoprevention trial of beta-carotene and vitamin A with lung cancer as the primary outcome. Participants at high risk for lung cancer are drawn from two populations: asbestos-exposed workers and heavy smokers. The intervention is a daily combination of 30 mg beta-carotene and 25,000 IU vitamin A as retinyl palmitate. Nearly 18,000 participants will be followed for a mean 6 years, yielding over 100,000 person-years of follow-up. We project that this sample size will have 80% power to detect a 23% decrease in the incidence of lung cancer cases. The purpose of this paper is to present the values of the key sample size parameters of CARET; our schemes for monitoring CARET for sample size adequacy, incidence of side effects, and efficacy of the study vitamins; an overview of the data collected; and plans for the primary, secondary, and ancillary analyses to be performed at the end of the trial. These approaches to the design, monitoring, and analysis of CARET are applicable for many other prevention trials.

Topics: Aged; Anticarcinogenic Agents; Asbestos; beta Carotene; Carotenoids; Diterpenes; Double-Blind Method; Female; Humans; Lung Neoplasms; Male; Middle Aged; Research Design; Retinyl Esters; Risk Factors; Smoking; Vitamin A

Because of their larger study populations and longer durations, prevention trials typically are more costly than treatment trials. Thus it is important to analyze costs systematically to aid in making cost-effective decisions during the conduct of prevention trials as well as in the original design. Cost analysis must be tied to sample size estimation because costs depend on such factors as the total number of person-years of follow-up and the number of trial outcomes, which are not basic design parameters but are derived quantities resulting from sample size estimation. We illustrate the use of cost analysis to decide among options for future conduct of an ongoing prevention trial with three issues that have arisen during the Carotene and Retinol Efficacy Trial (CARET): the trade-off between extending the duration of the trial or increasing the number of participants, the effect on costs of delay in accrual, and the cost effectiveness of particular retention activities.

Topics: Anticarcinogenic Agents; Asbestos; beta Carotene; Carotenoids; Costs and Cost Analysis; Diterpenes; Double-Blind Method; Humans; Lung Neoplasms; Patient Compliance; Randomized Controlled Trials as Topic; Retinyl Esters; Risk Factors; Smoking; Time Factors; Vitamin A

Epidemiologic studies have demonstrated an inverse relation between vitamin A intake and lung cancer rate. There is strong evidence that the provitamin A, beta-carotene, plays a more important role in the protective effect than vitamin A itself. The anticarcinogenic properties of beta-carotene have so far been attributed to its scavenger properties in deactivating or trapping reactive chemical species such as singlet oxygen and certain organic free radicals. Smoking results in increased excretion of detoxification products of electrophilic agents (mercapturic acids) in urine. Since reactive electrophilic intermediates are involved in carcinogenesis, we performed a double-blind, placebo-controlled intervention trial to investigate whether the intake of beta-carotene by smokers would affect urinary thioether excretion. Before the intervention the beta-carotene group (n = 62) and the placebo group (n = 61) had similar thioether excretion levels in urine (4.2 vs 4.3 mmolSH/mol creatinine). During the intervention (20 mg beta-carotene daily for 14 weeks) the placebo group showed a 12% increase, whereas the beta-carotene group showed a 5% decrease (P = 0.004). After the intervention the beta-carotene group had a 15% lower thioether excretion level than the placebo group (4.1 vs 4.7 mmolSH/mol creatinine; P = 0.0017). Our study shows that urinary thioether excretion varies considerably over time, and that smokers have a decreased excretion of thioethers in urine after the use of beta-carotene.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; beta Carotene; Carotenoids; Double-Blind Method; Humans; Lung Neoplasms; Male; Risk Factors; Smoking; Sulfides

Topics: Aged; Anticarcinogenic Agents; Asbestos; beta Carotene; Carotenoids; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Occupational Diseases; Smoking; United States; Vitamin A

Topics: Anticarcinogenic Agents; Asbestos; beta Carotene; Carotenoids; Clinical Protocols; Cohort Studies; Double-Blind Method; Female; Humans; Lung Neoplasms; Male; Middle Aged; Occupational Diseases; Patient Compliance; Sputum; United States; Vitamin A

We evaluated as functions of age and gender participation and adherence rates in older adults recruited to pilot studies for CARET, a multicenter chemoprevention trial. Eligible were men and women aged 50-69 who were current or recent former smokers, and men aged 45-74 with occupational exposure to asbestos. We found negligible differences by age in response to recruitment mailings, drop out during the enrollment process and after randomization, and adherence to taking the study capsules. Men had numerically lower drop-out and higher adherence rates than women, but differences were not statistically significant. These results should encourage researchers to recruit older men and women (at least up to age 69) to clinical trials.

Topics: Age Factors; Aged; beta Carotene; Carotenoids; Clinical Trials as Topic; Community Participation; Female; Humans; Lung Neoplasms; Male; Middle Aged; Patient Compliance; Pilot Projects; Primary Prevention; Sex Factors; Vitamin A

CARET is a two-armed, double-blind, randomized chemo-prevention trial to test the hypothesis that oral administration of beta-carotene 30 mg/day plus retinyl palmitate 25,000 IU/day will decrease the incidence of lung cancer in high-risk populations: heavy smokers and asbestos-exposed workers who have smoked. The agents combine anti-oxidant and nuclear tumor suppressor mechanisms. Fastidious monitoring for possible side effects is facilitated by inclusion of a Vanguard population. As of 31 December 1990, 6,105 participants of the 18,000 needed have been randomized in the trial. Efficacy results are expected in 1999.

Topics: Aged; Asbestos; beta Carotene; Carotenoids; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Occupational Exposure; Smoking; Vitamin A

Topics: Animals; Antineoplastic Agents; beta Carotene; Carotenoids; Clinical Trials as Topic; Diet Therapy; Humans; Lung Neoplasms; Trace Elements; Vitamins

Topics: Aspirin; beta Carotene; Cardiovascular Diseases; Carotenoids; Clinical Trials as Topic; Double-Blind Method; Humans; Lung Neoplasms; Prospective Studies

Disruption of ribosomal DNA (rDNA) has been linked to a variety of diseases in humans, including carcinogenesis. To evaluate the associations between rDNA copy number (CN) and risk of lung cancer, we measured 5.8S and 18S rDNA CN in the peripheral blood of 229 incident lung cancer cases and 1:1 matched controls from a nested case-control study within a prospective cohort of male smokers. There was a dose-response relationship between quartiles of both 18S and 5.8S rDNA CN and risk of lung cancer (odds ratio [OR], 95% confidence interval [CI]: 18S: 1.0 [ref]; 1.2 [0.6-2.1]; 1.8 [1.0-3.4]; 2.3 [1.3-4.1; Ptrend = 0.0002; 5.8S: 1.0 [ref]; 1.6 [0.8-2.9]; 2.2 [1.1-4.2]; 2.6 [1.3-5.1]; Ptrend = 0.0001). The associations between rDNA CN and lung cancer risk were similar when excluding cases diagnosed within 5 years of follow-up, and when stratifying by heavy (>20 cigarettes per day) and light smokers (≤20 cigarettes per day). We are the first to report that rDNA CN may be associated with future risk of lung cancer. To further elucidate the relationship between rDNA and lung cancer, replication studies are needed in additional populations, particularly those that include non-smokers.

Topics: Aged; alpha-Tocopherol; beta Carotene; Carcinogenesis; Case-Control Studies; Cohort Studies; Dietary Supplements; DNA Copy Number Variations; DNA, Ribosomal; Finland; Humans; Lung Neoplasms; Male; Middle Aged; Risk Factors; Smoking

Although interventional trials demonstrated that moderate-dose β-carotene supplementation increases lung cancer mortality in smokers and asbestos-exposed workers, differences in serum concentrations in absence of supplementation have not been studied in asbestos-exposed workers.. A mortality analysis was performed to assess the relationship of nonsupplemented serum β-carotene to all-cause and cancer mortalities using 1981 to 1983 serum β-carotene concentration measurements from 2,646 U.S. white male insulators (mean age, 57.7 years). Multivariable-adjusted Cox proportional hazard models that included terms for age, duration of asbestos exposure, smoking, season, and region were fitted to estimate mortality HRs and 95% confidence intervals (CI) according to serum β-carotene concentrations.. Median follow-up was 12.8 years and 984 (33.8%) subjects died during the follow-up period, including 415 deaths from overall cancer and 219 deaths from lung cancer. The overall mortality HR for a serum β-carotene increase of 10 μg/dL was 0.97 (95% CI, 0.96-0.99). Compared with the lowest quartile, HRs were 0.90 (95% CI, 0.76-1.07) for the second (38-65 μg/dL), 0.80 (95% CI, 0.67-0.96) for the third (66-104 μg/dL), and 0.63 (95% CI, 0.51-0.77) for the highest serum β-carotene quartile (≥105 μg/dL). There was no association between serum β-carotene and overall cancer mortality (HR, 1.00; 95% CI, 0.97-1.02) or lung cancer mortality (HR, 0.99; 95% CI, 0.96-1.02).. Higher nonsupplemented serum β-carotene concentrations were negatively associated with all-cause mortality among asbestos-exposed individuals.. Serum β-carotene can be a marker of one or more determinants of reduced mortality in asbestos-exposed workers. Cancer Epidemiol Biomarkers Prev; 24(3); 555-60. ©2014 AACR.

Topics: Asbestos; beta Carotene; Canada; Cohort Studies; Humans; Lung Neoplasms; Male; Middle Aged; Occupational Diseases; Proportional Hazards Models; Risk Factors; United States

Baeckea frutescens is a natural remedy recorded to be used in curing various health conditions. In Peninsular Malaysia, B. frutescens is found on the mountain tops, quartz ridge and sandy coasts. To our knowledge, there is only limited published literature on B. frutescens.. B. frutescens leaf crude methanol and its fractionated extracts (hexane, ethyl acetate and water) were prepared. Folin-Ciocalteau's method was used for the measurement of total phenolic content of the extracts. The antioxidant activity was measured by the scavenging activity on DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals, reducing power assay through the Prussian blue complex formation, the metal chelating assay as well as the β-Carotene-linoleic acid system assay. The cytotoxic activity of the extracts were evaluated against two lung carcinoma cell lines with varying molecular characteristics using the MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay. Lastly the toxicity of the crude methanol extract was evaluated using the acute oral toxicity experiment.. The methanolic extract with highest phenolic content showed the strongest β-carotene bleaching inhibition, whilst the water extract exhibited the highest activity in metal chelating and reducing power assays. The hexane extract displayed a mild cytotoxic effect on both A549 and NCI-H1299 human lung carcinoma cell lines. No mortalities and no adverse effects were observed in the acute oral toxicity investigation at the highest dose of 5000 mg/kg.. The findings in the present study suggest B. frutescens may be considered as a safe source of compounds with antioxidant and cytotoxic properties for therapeutic and functional food applications.

Topics: Antineoplastic Agents, Phytogenic; Antioxidants; beta Carotene; Biphenyl Compounds; Humans; Lung Neoplasms; Myrtaceae; Oxidation-Reduction; Phenols; Phytotherapy; Picrates; Plant Extracts; Plant Leaves

The aim of this study was to compare the dietary intake and serum levels of some selected carotenoids of lung cancer patients with healthy subjects. Thirty-five lung cancer patients and 33 healthy people were enrolled into this case-control study. Daily intake of nutrients was estimated using a semiquantitative food frequency questionnaire and a 3-day 24-h food recall questionnaire. The concentration of serum beta-carotene and lycopene were analyzed using a high performance liquid chromatography method. Case and control groups did not differ by the means of age, gender, smoking habits, weight, body mass index, mean daily energy intake, mean daily fat intake, and the percentage of daily energy provided by fat to total daily energy intake. The beta-carotene and lycopene intake of the case subjects was 96% and 195% greater than that of the control subjects. Daily intake of fruits and vegetables in the cancer group was higher than the control group. However, the serum concentration of 118% beta-carotene and 60% lycopene were higher in the control group. Despite a higher daily dietary intake of beta-carotene and lycopene by lung cancer patients, serum beta-carotene and lycopene concentrations were significantly lower than the group without cancer.

Topics: Adult; Aged; beta Carotene; Body Mass Index; Carotenoids; Case-Control Studies; Energy Intake; Female; Fruit; Humans; Lung Neoplasms; Lycopene; Male; Middle Aged; Nutrition Assessment; Surveys and Questionnaires; Vegetables

Experimental studies suggest that carotenoids and retinol may play a role in carcinogenesis, but epidemiological evidence is lacking. We investigated the prospective associations between plasma concentrations of major carotenoids and retinol, and overall and breast cancer risk. A nested case-control study included all first incident cancer cases diagnosed in the SU.VI.MAX cohort between 1994 and 2002 (n = 159 cases, 1 matched control/case). Baseline plasma concentrations of carotenoids and retinol were measured by high-performance liquid chromatography. Conditional logistic regression was used to assess odds ratios for an increase of 0.1 μmol/L [odds ratio (OR)] and 95% confidence intervals (CI). Plasma β-carotene (OR = 0.95, 95% CI = 0.90-0.99, Ptrend = 0.04) and β-cryptoxanthin concentrations (OR = 0.89, 95% CI = 0.81-0.99, Ptrend = 0.03) were inversely associated with overall cancer risk. Plasma β-cryptoxanthin concentration was inversely associated with breast cancer risk (OR = 0.83, 95% CI = 0.71-0.96, Ptrend = 0.02). The OR between plasma lycopene concentration and overall cancer risk was 1.07 (0.99-1.15), Ptrend = 0.06. This association turned significant (Ptrend = 0.01) when excluding cancer cases diagnosed during the first year of follow-up. This prospective study suggests an inverse association between plasma concentrations of β-cryptoxanthin and both overall and breast cancer risk, and an inverse association between β-carotene and overall cancer risk. The direct association between lycopene concentration and cancer risk deserves further investigation.

Topics: Adult; beta Carotene; Body Mass Index; Breast Neoplasms; Carotenoids; Case-Control Studies; Chromatography, High Pressure Liquid; Colorectal Neoplasms; Cryptoxanthins; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Logistic Models; Lung Neoplasms; Lycopene; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Factors; Vitamin A

Vitamin D may prolong cancer survival by inhibiting tumor progression and metastasis, however, there are limited epidemiologic studies regarding the association between circulating 25-hydroxyvitamin D (25(OH)D) and lung cancer survival. The aim of this study was to examine the relationship between serum 25(OH)D and lung cancer specific survival and to evaluate whether vitamin D binding protein (DBP) concentration modified this association.. 25(OH)D and DBP were measured in fasting serum samples from 500 male lung cancer cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for lung cancer related death according to quartiles of season-specific 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, a proxy for free circulating 25(OH)D.. Comparing highest to lowest quartiles, serum 25(OH)D (HR=1.18; 95% CI: 0.89-1.56) and DBP (HR=0.95; 95% CI: 0.71-1.26) were not associated with lung cancer survival and DBP concentration did not modify the association with 25(OH)D (p for interaction=0.56). There was suggestion of an association between higher serum 25(OH)D and better survival from adenocarcinoma (HR=0.64; 95% CI: 0.17-2.45) and small cell carcinoma (HR=0.55; 95% CI: 0.21-1.45), but these estimates were based on a relatively small number of cases.. Serum 25(OH)D was not associated with overall lung cancer survival regardless of DBP concentration, however, these findings should be examined in other studies that include women and subjects with higher 25(OH)D levels.

Topics: Aged; alpha-Tocopherol; beta Carotene; Case-Control Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Factors; Survival Analysis; Vitamin D; Vitamin D-Binding Protein

Preliminary studies have identified pro-surfactant protein B (pro-SFTPB) to be a promising blood biomarker for non-small-cell lung cancer. We conducted a study to determine the independent predictive potential of pro-SFTPB in identifying individuals who are subsequently diagnosed with lung cancer.. Pro-SFTPB levels were measured in 2,485 individuals, who enrolled onto the Pan-Canadian Early Detection of Lung Cancer Study by using plasma sample collected at the baseline visit. Multivariable logistic regression models were used to evaluate the predictive ability of pro-SFTPB in addition to known lung cancer risk factors. Calibration and discrimination were evaluated, the latter by an area under the receiver operating characteristic curve (AUC). External validation was performed with samples collected in the Carotene and Retinol Efficacy Trial (CARET) participants using a case-control study design.. Adjusted for age, sex, body mass index, personal history of cancer, family history of lung cancer, forced expiratory volume in one second percent predicted, average number of cigarettes smoked per day, and smoking duration, pro-SFTPB (log transformed) had an odds ratio of 2.220 (95% CI, 1.727 to 2.853; P < .001). The AUCs of the full model with and without pro-SFTPB were 0.741 (95% CI, 0.696 to 0.783) and 0.669 (95% CI, 0.620 to 0.717; difference in AUC P < .001). In the CARET Study, the use of pro-SFPTB yielded an AUC of 0.683 (95% CI, 0.604 to 0.761).. Pro-SFTPB in plasma is an independent predictor of lung cancer and may be a valuable addition to existing lung cancer risk prediction models.

Topics: Aged; Anticarcinogenic Agents; Area Under Curve; beta Carotene; Biomarkers, Tumor; Canada; Carcinoma, Non-Small-Cell Lung; Case-Control Studies; Early Detection of Cancer; Female; Humans; Logistic Models; Lung Neoplasms; Male; Middle Aged; Multicenter Studies as Topic; Multivariate Analysis; Odds Ratio; Predictive Value of Tests; Protein Precursors; Pulmonary Surfactant-Associated Proteins; Randomized Controlled Trials as Topic; Risk Factors; ROC Curve

Case-cohort designs select a random sample of a cohort to be used as control with cases arising from the follow-up of the cohort. Analyses of case-cohort studies with time-varying exposures that use Cox partial likelihood methods can be computer intensive. We propose a piecewise-exponential approach where Poisson regression model parameters are estimated from a pseudolikelihood and the corresponding variances are derived by applying Taylor linearization methods that are used in survey research. The proposed approach is evaluated using Monte Carlo simulations. An illustration is provided using data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of male smokers in Finland, where a case-cohort study of serum glucose level and pancreatic cancer was analyzed.

Topics: alpha-Tocopherol; Analysis of Variance; beta Carotene; Blood Glucose; Cohort Studies; Computer Simulation; Dietary Supplements; Finland; Health Surveys; Humans; Incidence; Lung Neoplasms; Male; Monte Carlo Method; Pancreatic Neoplasms; Regression Analysis; Smoking; Survival Analysis

Excess vitamin A may interrupt vitamin D-mediated transcription of target genes. This study investigated whether serum 25-hydroxyvitamin D [25(OH)D] concentrations were associated with lung cancer mortality, and whether this association varied by excess circulating vitamin A and vitamin A/β-carotene supplement use.. We analyzed 16,693 men and women in the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994. Lung cancer mortality (n = 258, 104 were former smokers and 23 were never smokers) were identified through National Death Index as of 2006. Serum 25(OH)D was measured by a radioimmunoassay. Vitamin A biomarkers including serum retinol, β-carotene, and retinyl esters were measured by HPLC. Supplement use for the past month was obtained by self-report. Multivariate-adjusted hazard ratios (HR) were estimated by Cox proportional hazard models.. There was no association of serum 25(OH)D with overall lung cancer mortality. Among nonsmokers, ≥44 vs. <44 nmol/L of serum 25(OH)D was associated with a decreased risk (HR = 0.53, 95 % CI = 0.31-0.92, former/never smokers and HR = 0.31, 95 % CI = 0.13-0.77, distant-former [quit ≥20 years]/never smokers). The associations were not observed among participants with excess circulating vitamin A (serum retinyl esters ≥7.0 μg/dL or the ratio of retinyl esters to retinol ≥0.08) or vitamin A/β-carotene supplement users. However, statistical evidence to support effect modification of vitamin A was less clear.. Serum 25(OH)D concentrations were inversely associated with lung cancer mortality in nonsmokers. The beneficial association was diminished among those with excess circulating vitamin A or vitamin A/β-carotene supplement users.

Topics: Adult; beta Carotene; Dietary Supplements; Female; Follow-Up Studies; Food-Drug Interactions; Humans; Lung Neoplasms; Male; Middle Aged; Nutrition Surveys; Proportional Hazards Models; Risk Factors; United States; Vitamin A; Vitamin D

Studying gene-environment interactions may provide insight about mechanisms underpinning the reported association between chromosome 15q24-25.1 variation and lung cancer susceptibility.. In a nested case-control study comparing 746 lung cancer cases to 1,477 controls, all of whom were non-Hispanic white smokers in the β-Carotene and Retinol Efficacy Trial, we examined whether lung cancer risk is associated with single nucleotide polymorphisms (SNPs) tagging the AGPHD1, CHRNA5, CHRNA3, and CHRNB4 genes and whether such risk is modified by diet and other characteristics. Intake of fruits and vegetables, their botanical groups, and specific nutrients were ascertained generally at baseline by food-frequency questionnaire.. Several sets of SNPs in high linkage disequilibrium were found: one set associated with a 27-34% increase and two sets associated with a 13-19% decrease in risk per minor allele. Associations were most prominent for the set including the non-synonymous SNP rs16969968. The rs16969968-lung cancer association did not differ by intake level of most dietary factors examined, but was stronger for individuals diagnosed at < 70 years of age or having a baseline smoking history of <40 cigarette pack-years.. Our data suggests that diet has little influence on the relation between chromosome 15q24-25.1 variation and lung cancer risk.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Aged; Alleles; beta Carotene; Case-Control Studies; Diet; Female; Genetic Predisposition to Disease; Humans; Lung Neoplasms; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk; Smoking

The decoction of the whole plant of Elephantopus mollis Kunth. is traditionally consumed to treat various free radical-mediated diseases including cancer and diabetes.. This study was initiated to determine whether the most effective antioxidant compound isolated from the whole plant of Elephantopus mollis can also contribute to its claimed traditional values as anticancer and antidiabetes agents.. An active antiradical phenolic compound (3,4-di-O-caffeoyl quinic acid) was isolated from the methanol extract (with the highest in polyphenolic content) and their antioxidant activities were compared using four different assays, that are DPPH, FRAP, metal chelating, and β-carotene bleaching tests. The compound was also evaluated for its cytotoxic activity, apoptotic induction and anti-glucosidase efficacies using methylene blue, DeadEnd™ assay and α-glucosidase assays, respectively.. The compound acted as a greater primary antioxidant than its methanol extract, by having higher ferric reducing activity (EC(50) 2.18±0.05 μg/ml), β-carotene bleaching activity (EC(50) 23.85±0.65 μg/ml) and DPPH scavenging activity (EC(50) 68.91±5.44μg/ml), whereas the methanol extract exhibited higher secondary antioxidant activity as a metal chelator with lower EC(50) value (49.39±3.68 μg/ml) than the compound. Cytotoxicity screening of this compound exhibited a remarkable dose-dependent inhibitory effect on NCI-H23 (human lung adenocarcinoma) cell lines (EC(50) 3.26±0.35 μg/ml) and was found to be apoptotic in nature based on a clear indication of DNA fragmentation. This compound also displayed a concentration-dependent α-glucosidase inhibition with EC(50) 241.80±14.29 μg/ml.. The findings indicate the major role of 3,4-di-O-caffeoyl quinic acid to antioxidant capacities of Elephantopus mollis extracts. The compound also exerted apoptosis-mediated cytotoxicity and α-glucosidase inhibitory effects and is thus a promising non toxic agent in treating cancer and type 2 diabetes mellitus.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; Asteraceae; beta Carotene; Biphenyl Compounds; Cell Line, Tumor; Chelating Agents; Chlorogenic Acid; DNA Fragmentation; Dose-Response Relationship, Drug; Enzyme Inhibitors; Ferric Compounds; Glycoside Hydrolase Inhibitors; Humans; Lung Neoplasms; Picrates; Plant Extracts; Polyphenols

The role of micronutrients in lung cancer prevention is controversial, as observational and experimental studies have generated contradicting results. These discrepancies between studies may be due to different effects of micronutrients depending on source (diet or supplements). The objective of this study was to evaluate the association between vitamin C, E, folate and beta-carotene and lung cancer risk while focusing on source-specific effects of dietary and supplemental intake. The association was evaluated in a cohort of 55,557 Danes who completed a food frequency questionnaire including information on consumption of vitamin C, E, folate and beta-carotene from diet and supplements. Incidence rate ratios of lung cancer were calculated using Cox proportional hazards models. During a median follow-up of 10.6 years, 721 incident lung cancer cases were diagnosed. We found a significant protective effect of dietary vitamin E intake and a significantly higher lung cancer risk with supplemental beta-carotene and dietary folate intake. All three micronutrients exhibited significant source-specific effects. The harmful effect of dietary folate is, however, most likely to be due to uncontrolled confounding. Our results indicate source-specific effects of vitamin E and beta-carotene in lung cancer prevention with a preventive effect of dietary vitamin E and a harmful effect of supplemental beta-carotene. Future studies on micronutrients and lung cancer should take source into account.

Topics: Aged; Anticarcinogenic Agents; Ascorbic Acid; beta Carotene; Cohort Studies; Denmark; Diet; Dietary Supplements; Female; Folic Acid; Humans; Lung Neoplasms; Male; Micronutrients; Middle Aged; Proportional Hazards Models; Vitamin E

Two primary prevention trials unexpectedly showed adverse effects of supplemental beta-carotene on lung cancer incidence in cigarette smokers. To elucidate the molecular mechanisms that might underlie these effects, we studied the immunohistochemical expression of cytochrome P450 1A1, 1A2, and 2E1, retinoic acid receptor beta, activated protein-1 elements, cyclin D1, and Ki67 in lung tumors and, when available, adjacent normal tissues obtained from incident cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Archival lung tissue was available from 52 men randomized to receive 20 mg of beta-carotene per day and 30 men randomized to the placebo arm, all of whom were diagnosed with incident non-small-cell lung carcinoma during the course of the trial and subsequently underwent radical pulmonary resection. In normal-appearing bronchial epithelium, positive staining for cyclin D1 was observed in 23% of cases in the beta-carotene group and 0% of cases in the placebo group (based on only 3 of 13 versus 0 of 11 cases staining positively, however; P = 0.04), with no differences in expression noted in lung tumor tissue (P = 0.48). There were no statistically significant differences in Ki67 expression in normal or cancerous lung tissue between intervention groups, although a small increase in staining in tumors was noted among cases in the beta-carotene versus placebo group (88% versus 71% of cases stained positive, respectively; P = 0.13). Contrary to expectation, beta-carotene supplementation had no apparent effect on retinoic acid receptor-beta expression. These findings suggest that male smokers supplemented with beta-carotene may have had an increased risk of lung cancer due to aberrant cell growth, although our results are based on a relatively small number of cases and require confirmation in other completed trials of beta-carotene supplementation.

Topics: Aged; alpha-Tocopherol; beta Carotene; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Cocarcinogenesis; Cyclin D1; Cytochromes; Dietary Supplements; Double-Blind Method; Humans; Ki-67 Antigen; Lung; Lung Neoplasms; Male; Middle Aged; Multicenter Studies as Topic; Neoplasm Proteins; Randomized Controlled Trials as Topic; Receptors, Retinoic Acid; Retrospective Studies; Smoking

A meta-analysis of four randomised trials in a total of 109 394 subjects showed a statistically significant increase in the risk of lung cancer among smokers who used dietary supplements containing beta-carotene, at a mean dose of 20 to 30 mg/day. This contradicts the results of observational studies conducted in the 1990s.

Topics: beta Carotene; Dietary Supplements; Humans; Lung Neoplasms; Smoking

Topics: Anticarcinogenic Agents; beta Carotene; Denmark; Dietary Supplements; Humans; Lung Neoplasms; Nutrition Policy; Vitamin D

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Colorectal Neoplasms; Confounding Factors, Epidemiologic; Dietary Supplements; Female; Folic Acid; Humans; Incidence; Lung Neoplasms; Male; Neoplasms; Primary Prevention; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Assessment; Selenium; United States; Vitamin B 12; Vitamin B 6; Vitamin E

Beta-Carotene supplementation showed neither benefit nor harm among apparently healthy physicians (all men) in the Physicians' Health Study (PHS) trial. The objective of the current investigation was to evaluate how long-term beta-carotene supplementation affects molecular markers of lung carcinogenesis in the PHS.. The protein levels of total p53, cyclin D1, proliferating cellular nuclear antigen (PCNA), retinoic acid receptor beta (RARbeta), and cytochrome p450 enzyme 1A1 (CYP1A1) were measured using the immunohistochemical method in 40 available archival lung tissue samples from patients who were diagnosed with lung cancer in the PHS. The protein levels of these markers were compared by category of beta-carotene treatment assignment and other characteristics using unconditional logistic regression models.. The positivity for total p53, RARbeta, cyclin D1, and PCNA was nonsignificantly lower among lung cancer patients who were assigned to receive beta-carotene than those who were assigned to receive beta-carotene placebo. There was a borderline significant difference in CYP1A1 positivity with an OR of 0.2 (95% confidence interval, 0.2-1.1; P = .06) in a comparison of men who received beta-carotene and men who received beta-carotene placebo.. The 50-mg beta-carotene supplementation on alternate days had no significant influence on molecular markers of lung carcinogenesis that were evaluated in the PHS. This finding provides mechanistic support for the main PHS trial results of beta-carotene, which demonstrated no benefit or harm to the risk of developing lung cancer.

Topics: beta Carotene; Biomarkers; Dietary Supplements; Female; Humans; Immunohistochemistry; Lung Neoplasms; Male; Middle Aged; Randomized Controlled Trials as Topic

High-dose beta-carotene supplementation in high-risk persons has been linked to increased lung cancer risk in clinical trials; whether effects are similar in the general population is unclear. The authors examined associations of supplemental beta-carotene, retinol, vitamin A, lutein, and lycopene with lung cancer risk among participants, aged 50-76 years, in the VITamins And Lifestyle (VITAL) cohort Study in Washington State. In 2000-2002, eligible persons (n = 77,126) completed a 24-page baseline questionnaire, including detailed questions about supplement use (duration, frequency, dose) during the previous 10 years from multivitamins and individual supplements/mixtures. Incident lung cancers (n = 521) through December 2005 were identified by linkage to the Surveillance, Epidemiology, and End Results cancer registry. Longer duration of use of individual beta-carotene, retinol, and lutein supplements (but not total 10-year average dose) was associated with statistically significantly elevated risk of total lung cancer and histologic cell types; for example, hazard ratio = 2.02, 95% confidence interval: 1.28, 3.17 for individual supplemental lutein with total lung cancer and hazard ratio = 3.22, 95% confidence interval: 1.29, 8.07 for individual beta-carotene with small-cell lung cancer for >4 years versus no use. There was little evidence for effect modification by gender or smoking status. Long-term use of individual beta-carotene, retinol, and lutein supplements should not be recommended for lung cancer prevention, particularly among smokers.

Topics: Aged; beta Carotene; Carotenoids; Dietary Supplements; Female; Humans; Lung Neoplasms; Lutein; Lycopene; Male; Middle Aged; Risk Factors; Smoking; Surveys and Questionnaires; Vitamin A; Vitamins

beta-Carotene has shown cancer-preventive effects in preclinical studies while increasing lung cancer mortality in clinical trials. We have shown that beta-carotene stimulates cAMP signalling in vitro. Here, we have tested the hypothesis that beta-carotene promotes the development of pulmonary adenocarcinoma (PAC) in vivo via cAMP signalling.. PAC was induced in hamsters with the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), followed by beta-carotene for 1.5 years. Incidence, multiplicity and size of lung tumours were recorded, and phosphorylated CREB and ERK1/2 in tumour cells were determined by Western blots. Cyclic AMP in blood cells was analysed by immunoassays, retinoids in serum and lungs by HPLC.. beta-Carotene increased lung tumour multiplicity, lung tumour size, blood cell cAMP, serum and lung levels of retinoids and induced p-CREB and p-ERK1/2 in lung tumours.. Our data suggest that beta-carotene promotes the development of PAC via increased cAMP signalling.

Topics: Adenocarcinoma; Animals; beta Carotene; Biological Assay; Blotting, Western; Cricetinae; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Extracellular Signal-Regulated MAP Kinases; Lung Neoplasms; Male; Mesocricetus; Models, Animal; Nitrosamines; Phosphorylation; Random Allocation; Retinoids; Signal Transduction; Time Factors

Studies have suggested that retinoids prevent lung cancer by interacting with nuclear retinoid receptors. However, clinical trials with beta-carotene increased lung cancer mortality. We recently showed that beta-carotene stimulates the proliferation of small airway-derived adenocarcinoma by increasing cAMP signaling. Here, we have tested the hypothesis that beta-carotene may stimulate squamous cell carcinoma cells via similar mechanisms. We determined the effects of beta-carotene in cell lines from squamous cell carcinomas and large airway epithelia on proliferation by MTT assays in the presence and absence of inhibitors. Signaling via cAMP/PKA was measured by immunoassays and PKA activation assay. Phosphorylated ERK1/2 was determined by Western blotting. beta-carotene significantly inhibited proliferation and phosphorylation of ERK1/2 by Galphas-mediated signaling involving adenylyl cyclase, cAMP, PKA and ERK1/2. These findings introduce a non-genomic inhibitory mechanism of beta-carotene and emphasize the need for the development of marker-guided lung cancer prevention.

Topics: beta Carotene; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Gene Expression Regulation, Neoplastic; Humans; Immunoassay; Lung Neoplasms; Models, Biological; Phosphorylation; Signal Transduction; Tetrazolium Salts; Thiazoles; Time Factors

Topics: Antioxidants; beta Carotene; Carotenoids; Evidence-Based Medicine; Humans; Life Style; Lung Neoplasms; Lutein; Lycopene; Risk; Vitamin A; Vitamins

Because US smoking rates have not declined during the past decade, there is a renewed need to identify factors associated with smoking cessation. Using a nested case-control design, we explored the association between ability to sustain cessation over an extended period and demographic, smoking, medical, and behavioral variables.. We selected a sample of 1379 sustained quitters (abstinent from smoking for at least 40 months) and 1388 relapsers (abstinent for more than 8 months before relapse) from participants in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study, a nutritional intervention study involving Finnish men aged 50 to 69 years at baseline. Contingency table and multiple regression analyses were used to evaluate potential differences between the 2 groups on baseline variables.. Compared with sustained quitters, relapsers were more likely to report symptoms of emotional distress and higher levels of nicotine dependence, to drink more alcohol, and to report more medical conditions.. Factors associated with both tobacco use and comorbid conditions impact an individual's ability to maintain long-term smoking cessation. Understanding the underlying mechanisms of action and potential common pathways among these factors may help to improve smoking cessation therapies.

Topics: Aged; alpha-Tocopherol; Attitude to Health; beta Carotene; Case-Control Studies; Finland; Health Behavior; Health Status; Humans; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Recurrence; Risk Factors; Risk-Taking; Smoking; Smoking Cessation; Smoking Prevention; Stress, Psychological; Time Factors; Tobacco Use Disorder

Reactive oxygen species produced either endogenously or exogenously can attack lipids, proteins and DNA in human cells and cause potentially deleterious consequences. In recent years, their role in the pathogenesis of lung cancer and the preventive effect of antioxidants have been studied extensively. In this study, our aim was to investigate the levels of 8-hydroxy-2'-deoxyguanosine (8OHdG) and malondialdehyde as a marker for the effects of reactive oxygen species on DNA and lipids, the levels of antioxidant vitamins and the correlations between these oxidative stress markers and antioxidants in lung cancer.. Serum malondialdehyde, beta-carotene, retinol, and vitamins C and E were measured by high-performance liquid chromatography methods in fasting blood samples and 8OHdG was measured by gas chromatography-mass spectrometry in 24-h urine samples of patients with lung cancer (n=39) and healthy controls (n=31).. The levels of 8OHdG and malondialdehyde were significantly higher (p<0.05 and p<0.005, respectively) and beta-carotene, retinol, and vitamins C and E (p<0.0001, p<0.0001, p<0.0001, and p<0.05, respectively) were significantly lower in patients than in controls. There was a significantly positive correlation between 8OHdG and malondialdehyde (r=0.463, p=0.01) and a negative correlation between the levels of 8OHdG and retinol (r=-0.419, p=0.021) in the patient group.. Our results demonstrate that the oxidant/antioxidant balance was spoiled in favor of lipid peroxidation and DNA damage in lung cancer patients. Significant increases in the levels of malondialdehyde and 8OHdG and decreases in the levels of antioxidants suggest the possible involvement of oxidative stress in lung cancer.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Case-Control Studies; Chromatography, High Pressure Liquid; Deoxyguanosine; DNA Damage; Female; Humans; Lipid Peroxidation; Lung Neoplasms; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Reactive Oxygen Species; Reference Values; Vitamin A; Vitamin E; Vitamins

Lycopene has been shown to inhibit tumor metastasis in vitro, but it is unclear whether lycopene is antimetastatic in vivo. Here, nude mice were orally supplemented 2 times per week for 12 wk with a low or high dose of lycopene [1 or 20 mg/kg body weight (BW)] or with beta-carotene (20 mg/kg BW). Two weeks after the beginning of supplementation, mice were injected once with human hepatoma SK-Hep-1 cells via the tail vein. Plasma levels of matrix metalloproteinase (MMP)-2 and vascular endothelial growth factor (VEGF) increased gradually in tumor-injected mice (tumor controls) following tumor injection but were markedly lowered by lycopene or beta-carotene supplementation. Ten weeks after tumor injection, mice were killed and tumor metastasis was found to be confined to the lungs. Compared with the tumor controls, high-lycopene supplementation lowered the mean number of tumors from 14 +/- 8 to 3 +/- 5 (P < 0.05) and decreased tumor cross-sectional areas by 62% (P < 0.05). High-lycopene supplementation also decreased the positive rate of proliferating cellular nuclear antigen (PCNA), the level of VEGF, and protein expressions of PCNA, MMP-9, and VEGF in lung tissues. However, high-lycopene increased the protein expression of nm23-H1 (an antimetastatic gene) by 133% (P < 0.001). For most variables measured, effects of lycopene were dose dependent and the effect of beta-carotene was between those of high-dose and low-dose lycopene. These results show that lycopene supplementation reduces experimental tumor metastasis in vivo and suggest that such an action is associated with attenuation of tumor invasion, proliferation, and angiogenesis.

Topics: Animals; beta Carotene; Body Weight; Carcinoma, Hepatocellular; Carotenoids; Cell Line, Tumor; Diet; Dietary Supplements; Gene Expression Regulation; Humans; Interleukin-12; Lung Neoplasms; Lycopene; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Nude; Neoplasm Metastasis; Neoplasms, Experimental; NM23 Nucleoside Diphosphate Kinases; Proliferating Cell Nuclear Antigen; Vascular Endothelial Growth Factor A

Insulin-like growth factor 1 (IGF-1) and its major binding protein, IGF binding protein 3 (IGFBP-3) are implicated in lung cancer and other malignancies. We have previously shown that the combination of three major antioxidants [beta-carotene (BC), alpha-tocopherol (AT) and ascorbic acid (AA)] can prevent lung carcinogenesis in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-treated and smoke-exposed (SM) ferret model, which is highly analogous to humans. The present study is aimed at determining the effect of the combination of BC, AT and AA on antioxidant capacity, lymphocyte DNA damage, plasma IGF-1 and IGFBP-3 concentrations, as well as on IGF-1/IGFBP-3 mRNA expression in the tissues (lung and liver) of the ferrets. Ferrets were treated with or without combined antioxidant (BC, AT and AA) supplementation (AOX) for 6 months in the following 4 groups: (i) control; (ii) SM+NNK; (iii) AOX; and (iv) SM+NNK+AOX. Combined AOX supplementation significantly attenuated SM+NNK induced lymphocyte DNA damage in the ferret, while increasing resistance to oxidative damage when challenged with H(2)O(2) in vitro. Ferrets treated with SM+NNK had significantly lower IGFBP-3 mRNA expression in lungs, whereas there was significantly higher IGFBP-3 mRNA expression in the liver, as well as higher circulating IGFBP-3 concentrations. Combined AOX supplementation did not affect the plasma or tissue (lung and liver) ratio of IGF-1/IGFBP-3. Combined antioxidant supplementation provides protection against smoke-induced oxidative DNA damage, but does not affect the IGF-1/IGFBP-3 system. Differential expression of IGFBP-3 in different tissues indicates that caution should be taken when using plasma IGFBP-3 as a biomarker of tissue status.

Topics: Animals; Antioxidants; Ascorbic Acid; beta Carotene; Disease Models, Animal; DNA Breaks, Single-Stranded; Ferrets; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Liver; Lung; Lung Neoplasms; Male; Nitrosamines; Smoke; Vitamin E

Topics: Antioxidants; beta Carotene; Clinical Trials as Topic; Dietary Supplements; Drug Approval; Evidence-Based Medicine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lung Neoplasms; Macular Degeneration; Risk Reduction Behavior; Spain

Lung cancer is the most common cause of cancer death in the United States. Cigarette smoking is the main risk factor. Former smokers are at a substantially increased risk for lung cancer compared with lifetime never-smokers. Chemoprevention is the use of specific agents to reverse, suppress, or prevent the process of carcinogenesis. This article reviews the major agents that have been studied for chemoprevention.. Articles of primary, secondary, and tertiary prevention trials were reviewed and summarized to obtain recommendations.. None of the phase III trials with the agents beta carotene, retinol, 13-cis-retinoic acid, alpha-tocopherol, N-acetylcysteine, or acetylsalicylic acid has demonstrated beneficial, reproducible results. For facilitating the evaluation of promising agents and for lessening the need for a large sample size, extensive time commitment, and expense, focus is now turning toward the assessment of surrogate end point biomarkers for lung carcinogenesis. With the understanding of important cellular signaling pathways, various inhibitors that may prevent or reverse lung carcinogenesis are being developed.. By integrating biological knowledge, more trials can be performed in a reasonable time frame. The future of lung cancer chemoprevention should entail the evaluation of single agents or combinations that target various pathways while working toward identification and validation of intermediate end points.

Topics: Acetylcysteine; alpha-Tocopherol; Anticarcinogenic Agents; Aspirin; beta Carotene; Chemoprevention; Clinical Trials, Phase III as Topic; Evidence-Based Medicine; Humans; Isotretinoin; Lung Neoplasms; United States; Vitamin A

In this study, we examined oxidative stress and B vitamins status in non-small cell lung cancer (NSCLC) patients at different stages. NSCLC patients were divided into 2 groups, stage III (IIIA + IIIB, n = 27) and stage IV (n = 23). A total of 16 healthy control subjects were included for comparison. Plasma levels of alpha-tocopherol, beta-carotene, vitamin C, Se, Cu, Zn, reduced glutathione (GSH), oxidized glutathione (GSSG), lipid oxidation and the activities of glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase, and xanthine oxidase (XO) were determined for evaluating oxidative status in these subjects. B vitamins (B(1), B(2), B(6), B(12), folate) in blood and plasma ghrelin level in these subjects were analyzed. Results showed that plasma level of ghrelin and lipid oxidation in NSCLC patients were significantly greater than control groups (P < 0.05). The activity of GPX, SOD, or catalase was significantly reduced, but XO activity was significantly elevated in NSCLC patients (P < 0.05). Plasma level of GSH was significantly lower, but GSSG level was significantly increased in NSCLC patients (P < 0.05). Vitamins B(2) and B(6) levels in red blood cells (RBC) from NSCLC patients were significantly lower (P < 0.05), and both were negatively correlated with plasma ghrelin. The correlation coefficients were -0.788 and -0.752, respectively. These data suggest that plasma GSH level may be a proper biomarker for evaluating oxidation status for NSCLC patients. RBC levels of vitamins B2 and B6 were reduced in NSCLC patients; thus, the importance of vitamins B(2) and B(6) for NSCLC patients could not be ignored.

Topics: Adult; Aged; Aged, 80 and over; alpha-Tocopherol; Ascorbic Acid; beta Carotene; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Case-Control Studies; Catalase; Erythrocytes; Female; Ghrelin; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Health Status; Humans; Lipid Peroxidation; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Nutritional Status; Oxidation-Reduction; Oxidative Stress; Superoxide Dismutase; Vitamin B Complex; Xanthine Oxidase

An alpha-tocopherol, beta-carotene supplementation trial (ATBC) and a chemoprevention trial with beta-carotene and retinoids (CARET trial) were conducted in the 1990s in populations at risk for the development of lung cancer. Both trials had to be discontinued due to significant increases in lung cancer and cardiovascular mortality. Clinical trials to test the cancer preventive effects of beta-carotene are still ongoing, and high concentrations of this provitamin are contained in numerous dietary supplements. Using a cell line derived from a human pulmonary adenocarcinoma (PAC) of Clara cell lineage and immortalized human small airway epithelial cells, our data show that low concentrations of beta-carotene that can be realistically expected in human tissues after oral administration caused a significant increase in intracellular cAMP and activated PKA, as well as in phosphorylation of ERK1/2 and CREB. Furthermore, the proliferation of cells was significantly stimulated by identical concentrations of beta-carotene as monitored by MTT assays. Control experiments with retinol also showed stimulation of cell proliferation and activation of PKA in both cell lines. In light of the fact that PAC is the leading type of lung cancer, these findings suggest that the growth promoting effects of beta-carotene on this cancer type observed in our experiments may have contributed to the unfortunate outcome of the ATBC and CARET trials. This interpretation is supported by the fact that elevated levels of cAMP in the cardiovascular system play a major role in the genesis of cardiovascular disease, which was also greatly promoted in the CARET trial. Our data challenge the widely accepted view that beta-carotene may be useful as a cancer preventive agent.

Topics: Adenocarcinoma; Analysis of Variance; beta Carotene; Blotting, Western; Cell Line; Cell Line, Tumor; Cell Proliferation; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Cyclic AMP-Dependent Protein Kinases; Dose-Response Relationship, Drug; Enzyme Activation; Epithelial Cells; Humans; Lung; Lung Neoplasms; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Phosphorylation; Protein Serine-Threonine Kinases; Time Factors; Vitamins

Interactions among beta-carotene (BC), alpha-tocopherol (AT) and ascorbic acid (AA) led to the hypothesis that using a combination of these antioxidants could be more beneficial than using a single antioxidant alone, particularly against smoke-related lung cancer. In this investigation, we have conducted an animal study to determine whether combined BC, AT and AA supplementation (AOX) protects against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung carcinogenesis in smoke-exposed (SM) ferrets. Ferrets were treated for 6 months in the following four groups: (i) control, (ii) SM + NNK, (iii) AOX and (iv) SM + NNK + AOX. Results showed that the combined AOX supplementation (i) prevented the SM + NNK-decreased lung concentrations of retinoic acid (RA) and BC; (ii) inhibited the SM + NNK-induced phosphorylation of Jun N-terminal kinase (JNK), extracellular-signal-regulated protein kinase (ERK) and proliferating cellular nuclear antigen proteins in the lungs of ferrets; and (iii) blocked the SM + NNK-induced up-regulation of total p53 and Bax proteins, as well as phosphorylated p53 in the lungs of ferrets. In addition, there were no lesions observed in the lung tissue of ferrets in the control and/or the AOX groups after 6 months of intervention, but combined AOX supplementation resulted in a trend toward lower incidence of both preneoplastic lung lesions and lung tumor formation in SM + NNK + AOX group of ferrets, as compared with the SM + NNK group alone. These data indicate that combined AOX supplementation could be a useful chemopreventive strategy against lung carcinogenesis through maintaining normal tissue levels of RA and inhibiting the activation of mitogen-activated protein kinase pathways, cell proliferation and phosphorylation of p53.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; bcl-2-Associated X Protein; beta Carotene; Blotting, Western; Carcinogens; Chromatography, High Pressure Liquid; Dietary Supplements; Enzyme Activation; Ferrets; Immunohistochemistry; JNK Mitogen-Activated Protein Kinases; Lung; Lung Neoplasms; Mitogen-Activated Protein Kinases; Nitrosamines; Proliferating Cell Nuclear Antigen; Tobacco Smoke Pollution; Tretinoin; Tumor Suppressor Protein p53

Topics: Antineoplastic Agents; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; beta Carotene; Breast Neoplasms; Clinical Trials as Topic; Estrogen Receptor Modulators; Female; Humans; Lung Neoplasms; Male; Smoking; Tamoxifen; Vitamin A

The Bach model was developed to predict the absolute 10-year risk of developing lung cancer among smokers by use of participants in the Carotene and Retinol Efficacy Trial of lung cancer prevention. We assessed the validity of the Bach model among 6239 smokers from the placebo arm of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. The expected numbers of lung cancer cases and deaths without lung cancer were calculated from the Bach model and compared with the observed numbers of corresponding events over 10 years. We found that the risk model slightly underestimated the observed lung cancer risk (number of lung cancers expected/number observed = 0.89, 95% confidence interval [CI] = 0.80 to 0.99) over 10 years. The competing risk portion of the model substantially underestimated risk of non-lung cancer mortality (number of non-lung cancer deaths expected/number observed = 0.61, 95% CI = 0.57 to 0.64) over 10 years. The age-specific concordance indices for 10-year predictions were 0.77 (95% CI = 0.70 to 0.84), 0.59 (95% CI = 0.53 to 0.65), 0.62 (95% CI = 0.57 to 0.67), and 0.57 (95% CI = 0.49 to 0.67) for the age groups 50-54, 55-59, 60-64, and 65-69 years, respectively. Periodic radiographic screening in the ATBC Study may explain why slightly more cancers were observed than expected from the Bach model.

Topics: Age Distribution; Age Factors; Aged; alpha-Tocopherol; Anticarcinogenic Agents; beta Carotene; Clinical Trials as Topic; Confidence Intervals; Humans; Incidence; Lung Neoplasms; Mass Chest X-Ray; Middle Aged; Models, Statistical; Predictive Value of Tests; Reproducibility of Results; Risk Assessment; Risk Factors; Smoking; United States

Results from some intervention trials indicated that supplemental beta-carotene enhanced lung cancer incidence and mortality in chronic smokers. The aim of this study was to verify the hypothesis that high concentrations of the carotenoid, under the pO2 present in lung (100-150 mmHg), may exert deleterious effects through a prooxidant mechanism. To test this hypothesis, we examined the interactions of beta-carotene and cigarette smoke condensate (tar) on the formation of lipid peroxidation products in rat lung microsomal membranes enriched in vitro with varying beta-carotene concentrations (from 1 to 10 nmol/mg prot) and then incubated with tar (6-25 microg/ml) under different pO2. As markers of lipid peroxidation, we evaluated the levels of conjugated dienes and malondialdehyde, possessing mutagenic and pro-carcinogenic activity. The exposure of microsomal membranes to tar induced a dose-dependent enhancement of lipid peroxidation, which progressively increased as a function of pO2. Under a low pO2 (15 mmHg), beta-carotene acted clearly as an antioxidant, inhibiting tar-induced lipid peroxidation. However, the carotenoid progressively lost its antioxidant efficiency by increasing pO2 (50-100 mmHg) and acted as a prooxidant at pO2 ranging from 100 to 760 mmHg in a dose-dependent manner. Consistent with this finding, the addition of alpha-tocopherol (25 microM) prevented the prooxidant effects of the carotenoid. beta-Carotene auto-oxidation, measured as formation of 5,6-epoxy-beta,beta-carotene, was faster at high than at low pO2 and the carotenoid was more rapidly consumed in the presence of tar. These data point out that the carotenoid may enhance cigarette smoke-induced oxidative stress and exert potential deleterious effects at the pO2 normally present in lung tissue.

Topics: alpha-Tocopherol; beta Carotene; Humans; Lipid Peroxides; Lung; Lung Neoplasms; Malondialdehyde; Microsomes; Mutagens; Oxygen; Oxygen Consumption; Smoke; Smoking

Recent findings of an inverse association between beta-cryptoxanthin and lung cancer risk in several observational epidemiologic studies suggest that beta-cryptoxanthin could potentially act as a chemopreventive agent against lung cancer. However, the biological activity of beta-cryptoxanthin and molecular mechanism(s) by which beta-cryptoxanthin affects lung tumourigenesis have not been studied. In the present study, we found that beta-cryptoxanthin inhibited the growth of A549 cells, a non-small-cell lung cancer cell line and BEAS-2B cells, an immortalized human bronchial epithelial cell line in a dose-dependent manner. beta-Cryptoxanthin suppressed the protein levels of cyclin D1 and cyclin E, up-regulated the cell cycle inhibitor p21, increased the number of lung cancer cells in the G1/G0 phase and decreased those in the S phase of the cell cycle. Consistent with inhibition of the lung cancer cell growth, beta-cryptoxanthin induced the mRNA levels of retinoic acid receptor beta (RARbeta) in BEAS-2B cells, although this effect was less pronounced in A549 cells. Furthermore, beta-cryptoxanthin transactivated RAR-mediated transcription activity of the retinoic acid response element. These findings suggest a mechanism of anti-proliferative action of beta-cryptoxanthin and indicate that beta-cryptoxanthin may be a promising chemopreventive agent against lung cancer.

Topics: Anticarcinogenic Agents; Base Sequence; beta Carotene; Bronchi; Carcinoma, Non-Small-Cell Lung; Cell Division; Cryptoxanthins; Gene Expression Regulation, Neoplastic; Genes, Reporter; Humans; Luciferases; Lung Neoplasms; Molecular Sequence Data; Receptors, Retinoic Acid; Respiratory Mucosa; Up-Regulation; Xanthophylls

A number of epidemiological studies have reported associations of beta-carotene plasma levels or intake with decreased lung cancer risk. However, intervention studies in smokers reported increased lung tumor rates after high long-term beta-carotene supplementation. For insight into these conflicting results, we studied the influence of beta-carotene on tobacco smoke carcinogen-induced lung cancer development in the A/J-mouse using 4-(N-Methyl-N-nitro samino)-1-(3-pyridyl)-1-butanone (NNK) as the initiator and lung adenoma multiplicity as the functional endpoint. Gene regulation of the putative tumor suppressor RARbeta in mouse lung was analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for its relevance in predicting the endpoint of lung cancer. A/J-mice achieved plasma beta-carotene levels of up to 3 micromol/L within 4 wk and up to 6 micromol/L after 6 mo of supplementation on a diet modified to enhance beta-carotene absorption. Despite high lung beta-carotene concentrations of up to 6 micromol/kg, tumor multiplicity was not significantly affected by the beta-carotene treatment, either in carcinogen-initiated or non-initiated mice, and was unrelated to beta-carotene dose and the time point of treatment during cancer formation. Tumor multiplicity did not correlate with beta-carotene plasma levels in NNK-treated animals. All RARbeta isoforms were significantly suppressed in the lungs of NNK- and NNK plus high dose beta-carotene-treated animals. However, the number of tumors per mouse did not correlate with the RARbeta-isoform expression levels. beta-carotene alone after 3 mo of supplementation mildly but significantly increased levels of RARbeta1, beta2, and beta4. This increase persisted for 6 mo for RARbeta2 and beta4. In summary, we found no effect of beta-carotene on tumor formation in the NNK-initiated A/J-mouse lung cancer model with respect to dose or time point of treatment. beta-Carotene-induced changes in RARbeta isoform gene expression levels were not predictive for the number of lung tumors but were indicative of intact beta-carotene metabolism and persistent sensitivity to retinoic acid in the mice. Down-regulation of RARbeta in NNK-induced adenoma-bearing lungs was similar to that observed in human lung cancer and further confirms the A/J-mouse as a valuable model for lung carcinogenesis.

Topics: Adenoma; Animals; beta Carotene; Carcinogens; Dietary Supplements; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Lung; Lung Neoplasms; Male; Mice; Nitrosamines; Protein Isoforms; Random Allocation; Receptors, Retinoic Acid; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Smoking; Vitamins

We compared the effects of beta-carotene with those of beta-apo-8'-carotenal (AC, an oxidative product of beta-carotene) on DNA damage and the expression of cytochrome P450 (CYP)1A2 in A549 cells exposed or not to benzo[a]pyrene (BaP), a cigarette-associated carcinogen. Furthermore, we investigated whether quercetin, a flavonoid, modulates these effects. A549 cells were first preincubated with various concentrations of beta-carotene or AC for 1h, followed by incubation with 20 microM BaP for 24h. Next, DNA strand breaks, measured by use of the comet assay, and the expression of CYP1A2, measured by use of western blotting, were assessed. Both beta-carotene and AC at 20 microM significantly enhanced DNA strand breaks and CYP1A2 expression induced by BaP. However, beta-carotene at 2 microM significantly suppressed BaP-induced DNA strand breaks. AC alone induced DNA strand breaks, lipid peroxidation, and the expression of CYP1A2 in A549 cells. The harmful effects of beta-carotene and AC on intracellular DNA were associated with the expression of CYP, because 1-aminobenzotriazole, a CYP inhibitor, partly suppressed these effects. Quercetin significantly inhibited the DNA strand breaks and the increase in CYP1A2 protein induced by AC or beta-carotene in combination with BaP or by AC alone. These findings indicate that the harmful effect of beta-carotene induced by BaP may be through the formation of oxidative products such as AC. Quercetin increased the safety of high doses of beta-carotene, possibly through interaction with beta-carotene's oxidative products or through inhibition of CYP1A2 expression.

Topics: Antioxidants; Benzo(a)pyrene; beta Carotene; Blotting, Western; Carotenoids; Cell Line, Tumor; Comet Assay; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP1A2 Inhibitors; DNA Breaks; Drug Interactions; Enzyme Inhibitors; Humans; Lipid Peroxidation; Lung Neoplasms; Quercetin; Triazoles

Male strain A/J mice were exposed for six hours a day, five days a week for six months to either full tobacco smoke or to tobacco smoke drawn through a HEPA filter that removed more than 99% of particulate matter. After another four months in air, the animals were sacrificed and lung tumors were counted for calculation of multiplicities and incidences. Analysis of the chamber atmospheres showed that in the filtered smoke the concentrations of polycyclic aromatic hydrocarbons and tobacco smoke specific nitrosamines were reduced to from below 18% to even nondetectable levels of the original values measured in the unfiltered smoke. Aldehydes and other volatile organic compounds such as 1,3-butadiene, benzene, or acrolein were reduced to about 50 to 90% of the concentrations found in unfiltered smoke. Some potentially carcinogenic metals reached levels in filtered smoke ranging from 77% to less than 1% found in full smoke. The mice exposed to the filtered smoke atmosphere had practically identical lung tumor multiplicities and incidence as had the animals exposed to full smoke, significantly higher than in air exposed controls. Diets containing 0.5% beta-carotene or 0.4% N-acetylcysteine afforded some chemoprevention. It was tentatively concluded that 1,3-butadiene might be an important contributor to lung tumorigenesis in this mouse model of tobacco smoke carcinogenesis.

Topics: Acetylcysteine; Animals; Atmosphere Exposure Chambers; beta Carotene; Carcinogens; Free Radical Scavengers; Lung Neoplasms; Male; Metals; Mice; Nicotiana; Nitrosamines; Polycyclic Aromatic Hydrocarbons; Smoke

Topics: Asbestosis; beta Carotene; Dietary Supplements; Female; Humans; Lung Neoplasms; Male; Mortality; Sex Factors; Smoking

We studied the influence of beta-carotene on the tobacco smoke carcinogen 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor development in the A/J-mouse model. The normally low beta-carotene absorption was facilitated with a diet enriched in fat and bile salt, resulting in plasma and lung tissue levels similar to humans. beta-Carotene enhanced NNK-induced early bronchial cell proliferation, however, this effect was not predictive for later tumor development. Tumor multiplicity was not significantly affected by beta-carotene, neither in carcinogen-initiated nor in uninitiated mice, and regardless of dose and time point of supplementation during tumor development. RARbeta isoform and CYP26 gene expression levels analyzed by quantitative RT-PCR were weakly, but significantly, inversely correlated and showed evidence for altered retinoid signaling and catabolism in the lungs of NNK-initiated, beta-carotene supplemented mice. However, this interaction did not translate into enhanced tumor multiplicity. These results indicate that impaired retinoid signaling is not likely a key factor in lung tumorigenesis in this mouse model.

Topics: Adenoma; Animals; beta Carotene; Bronchi; Carcinogens; Cytochrome P-450 Enzyme System; Disease Models, Animal; Down-Regulation; Drug Interactions; Epithelial Cells; Gene Expression Regulation; Lung; Lung Neoplasms; Male; Mice; Nitrosamines; Protein Isoforms; Receptors, Retinoic Acid; Retinoic Acid 4-Hydroxylase

Topics: beta Carotene; Cardiovascular Diseases; Cataract; Humans; Lung Neoplasms; Lutein; Macular Degeneration; Radiodermatitis; Retinitis Pigmentosa; Xanthophylls; Zeaxanthins

Topics: alpha-Tocopherol; Antioxidants; beta Carotene; Head and Neck Neoplasms; Humans; Lung Neoplasms; Randomized Controlled Trials as Topic; Smoking; Vitamin A

Topics: Adult; beta Carotene; Carcinogens; Carotenoids; Female; France; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Primary Prevention; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Research Design; Smoking; United States

Intervention studies have demonstrated that, in smokers, beta-carotene supplements had a deleterious effect on risk of lung cancer and may have a deleterious effect on digestive cancers as well. We investigated a potential interaction between beta-carotene intake and smoking on the risk of tobacco-related cancers in women.. A total of 59,910 women from the French Etude Epidémiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N) prospective investigation were studied from 1994. After a median follow-up of 7.4 years, 700 women had developed cancers known to be associated with smoking. Diet, supplement use, and smoking status at baseline were assessed by self-report. beta-carotene intake was classified into four groups: first (low intake), second, and third tertiles of dietary intake, and use of supplements (high intake). Unadjusted and multivariable Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals (CIs) for cancer risk. All statistical tests were two-sided.. Among never smokers, multivariable hazard ratios of all smoking-related cancers were 0.72 (95% CI = 0.57 to 0.92), 0.80 (95% CI = 0.64 to 1.01), and 0.44 (95% CI = 0.18 to 1.07) for the second and third tertiles of dietary intake, and high beta-carotene intake, respectively, compared with low intake (Ptrend = .03). Among ever smokers, multivariable hazard ratios were 1.43 (95% CI = 1.05 to 1.96), 1.20 (95% CI = 0.86 to 1.67), and 2.14 (95% CI = 1.16 to 3.97) for the second and third tertiles of dietary intake, and high beta-carotene intake, respectively, compared with low intake (Ptrend = .09). Tests for interaction between beta-carotene intake and smoking were statistically significant (Ptrend =.017). In this population, the absolute rates over 10 years in those with low and high beta-carotene intake were 181.8 and 81.7 cases per 10,000 women in never smokers and 174.0 and 368.3 cases per 10,000 women in ever smokers.. beta-carotene intake was inversely associated with risk of tobacco-related cancers among nonsmokers with a statistically significant dose-dependent relationship, whereas high beta-carotene intake was directly associated with risk among smokers.

Topics: Adult; Antioxidants; beta Carotene; Carcinogens; Dietary Supplements; Feeding Behavior; Female; Follow-Up Studies; France; Humans; Lung Neoplasms; Middle Aged; Multivariate Analysis; Neoplasms; Odds Ratio; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Smoking

In the Alpha Tocopherol, Beta Carotene Cancer Prevention Study, alpha tocopherol supplementation decreased risk of cerebral infarction by 14% (95% CI, -25% to -1%), and beta carotene increased risk of intracerebral hemorrhage by 62% (95% CI, 10% to 132%). We report here the 6-year postintervention effects of alpha tocopherol and beta carotene supplementation on stroke and its subtypes.. A total of 29,133 male smokers, aged 50 to 69 years, were randomized to receive 50 mg of alpha tocopherol, 20 mg of beta carotene, both, or placebo daily for 5 to 8 years. At the beginning of the post-trial follow-up, 24 382 men were still at risk for first-ever stroke. During the post-trial follow-up, 1327 men experienced a stroke: 1087 cerebral infarctions, 148 intracerebral hemorrhages, 64 subarachnoid hemorrhages, and 28 unspecified strokes.. Post-trial risk for cerebral infarction was elevated among those who had received alpha tocopherol compared with those who had not (relative risk [RR], 1.13; 95% CI, 1.00 to 1.27), whereas beta carotene had no effect (RR, 0.97; 95% CI, 0.86 to 1.09). Alpha tocopherol supplementation was associated with a postintervention RR of 1.01 (95% CI, 0.73 to 1.39) for intracerebral hemorrhage and 1.38 (95% CI, 0.84 to 2.26) for subarachnoid hemorrhage. The corresponding RRs associated with beta carotene supplementation were 1.38 (95% CI, 0.99 to 1.91) and 1.09 (95% CI, 0.67 to 1.77), respectively.. Neither alpha tocopherol nor beta carotene supplementation had any postintervention preventive effects on stroke. The post-trial increase in cerebral infarction risk among recipients of alpha tocopherol may present a rebound of the reduced risk of cerebral infarction during the intervention.

Topics: alpha-Tocopherol; Antioxidants; beta Carotene; Cerebral Hemorrhage; Cerebral Infarction; Dietary Supplements; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk; Smoking; Stroke; Subarachnoid Hemorrhage

Topics: beta Carotene; Blindness; Clinical Trials as Topic; Contraindications; Dietary Supplements; Drug Labeling; Humans; Lung Neoplasms; Macular Degeneration; Male; Prostatic Neoplasms; Smoking; Zinc

Topics: Animals; Anticarcinogenic Agents; Antioxidants; beta Carotene; Carcinogens; Cardiovascular Diseases; Clinical Trials as Topic; Dietary Supplements; Disease Models, Animal; Female; Follow-Up Studies; Humans; Incidence; Lung; Lung Neoplasms; Male; Oxidants; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Smoking; United States

Topics: Anticarcinogenic Agents; beta Carotene; Carcinogens; Chemoprevention; Dietary Supplements; Humans; Lung Neoplasms; Male; Randomized Controlled Trials as Topic; Smoking; Treatment Failure

The Carotene and Retinol Efficacy Trial (CARET) was a large, multicenter randomized chemoprevention trial designed to test a combined lung cancer prevention agent in heavy smokers and workers exposed to asbestos. In January 1996, the CARET Steering Committee decided to stop the intervention due to an adverse effect. This paper describes the decision process used to apply the stopping rules and the activities engaged in by CARET participants and staff to implement the decision. The most important activity was to draft and mail a letter to the participants informing them of the disappointing CARET results and asking them to stop taking the study vitamins and to return any unused study vitamins. The steering committee, with the support of the National Cancer Institute, planned to follow participants for disease endpoints and smoking behavior for 5 years. These activities led to smooth closure of active intervention and maintained high retention rates during the transition.

Topics: Asbestos; beta Carotene; Chemoprevention; Clinical Trials Data Monitoring Committees; Data Interpretation, Statistical; Drug Evaluation; Ethics, Medical; Humans; Lung Neoplasms; Occupational Exposure; Randomized Controlled Trials as Topic; Smoking; Therapeutic Human Experimentation; United States; Vitamin A

The effects of ethyl alcohol and synthetic beta-carotene have been studied on two models of carcinogenesis in mice BALB/c. Lung tumours were induced with organotropically acting urethane (given by i.p. injections, total dose--100 mg/mouse) subcutaneous tumours were induced with locally acting benzo(a)pyrene (single injection, 2 mg/mouse) beta-Carotene was given 3 times per week 0.4 mg/mouse by gastric intubations and 10% ethanol was given instead of drinking water until the end of experiments (4-6 months). Results showed that beta-carotene did not significantly inhibit lung adenomogenesis and may moderately delay subcutaneous tumours occurence. In ourstudies chronic ethanol intake did notshow significant influence on this delay.

Topics: Animals; Benzo(a)pyrene; beta Carotene; Carcinogens; Ethanol; Liver; Lung Neoplasms; Mice; Mice, Inbred BALB C; Models, Animal; Skin Neoplasms; Urethane

To investigate whether high serum levels of carotenoids, tocopherols, and folic acid decrease risk of lung cancer in Japanese, we conducted a case-control study nested in the Japan Collaborative Cohort (JACC) Study. A total of 39,140 subjects provided serum samples at baseline between 1988 and 1990. We identified 147 cases (113 males and 34 females) of death from lung cancer during an 8-year follow-up. Of the subjects who survived to the end of this follow-up, 311 controls (237 males and 74 females) were selected, matched to each case of lung cancer death for gender, age and participating institution. We measured serum levels of antioxidants in cases of lung cancer death and controls. Odds ratios (ORs) for lung cancer death were estimated using conditional logistic models. The risk of lung cancer death for the highest quartile of serum alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, and canthaxanthin was significantly or marginally significantly lower than for the lowest quartile: the ORs, adjusted for smoking and other covariates, were 0.35 (95% confidence interval (CI), 0.14-0.88), 0.21 (0.08-0.58), 0.46 (0.21-1.04), 0.44 (0.17-1.16) and 0.37 (0.15-0.91), respectively. The ORs for the highest serum levels of zeaxanthin/lutein and folic acid tended to be low, but the differences were not statistically significant. Serum total cholesterol was also inversely related to risk of lung cancer death: the OR for the highest vs. the lowest quartile was 0.39 (95% CI, 0.19-0.79). Higher serum levels of carotenoids such as alpha- and beta-carotenes may play a role in preventing death from lung cancer among Japanese.

Topics: Adult; Aged; Alcohol Drinking; Anticarcinogenic Agents; Antioxidants; beta Carotene; Body Mass Index; Canthaxanthin; Carotenoids; Case-Control Studies; Cholesterol; Cohort Studies; Cryptoxanthins; Feeding Behavior; Female; Folic Acid; Follow-Up Studies; Humans; Japan; Life Style; Lung Neoplasms; Lutein; Lycopene; Male; Middle Aged; Odds Ratio; Smoking; Tocopherols; Vitamin A; Xanthophylls

Effect of beta-carotene on the inhibition of lung metastasis induced by B16F-10 melanoma cells was studied in C57BL/6 mice. Simultaneous administration of the compound after tumor induction produced a significant reduction (71.36%) in tumor nodule formation. Increased lung collagen hydroxyproline (22.37 microg/mg protein) in the metastasized lungs of control animals compared to the normal animals (0.95 microg/mg protein) was significantly reduced (4.19 microg/mg protein) in the beta-carotene treated animals. High amount of uronic acid (355.83 microg/100mg tissue ) in the metastasized control animals was significantly reduced (87.87 microg/100 mg tissue) in the animals treated with beta-carotene. Lung hexosamine content also was inhibited significantly in the beta-carotene treated animals (1.58 mg/100 mg lyophilized tissue) compared to the untreated control animals (4.2 mg/100 mg lyophilized tissue). The elevated levels of serum sialic acid and serum gamma glutamyl transpeptidase activity in the untreated control animals was significantly reduced in the animals treated with beta-carotene. Beta carotene treated animals were survived up to 69 days. Histopathology of the lung tissue also correlated with the above parameters and life span of the drug treated animals. Our results reveal the antimetastatic activity of beta-carotene which are abundantly present in green plants, vegetables and fruits.

Topics: Animals; beta Carotene; gamma-Glutamyltransferase; Hexosamines; Lung; Lung Neoplasms; Melanoma, Experimental; Mice; Mice, Inbred C57BL; N-Acetylneuraminic Acid; Neoplasm Transplantation; Survival Rate; Tropocollagen; Tumor Cells, Cultured; Uronic Acids

Topics: Anticarcinogenic Agents; Antioxidants; beta Carotene; Biomarkers; Chemoprevention; Confounding Factors, Epidemiologic; False Positive Reactions; Feeding Behavior; Follow-Up Studies; Fruit; Humans; Incidence; Lung Neoplasms; Prospective Studies; Smoking; Vegetables

Topics: Aged; Aged, 80 and over; Aging; Antioxidants; Ascorbic Acid; beta Carotene; Humans; Jaundice; Lung Neoplasms; Macular Degeneration; Middle Aged; Randomized Controlled Trials as Topic; Smoke Inhalation Injury; Vitamin E; Zinc

Topics: beta Carotene; Contraindications; Dietary Supplements; Humans; Lung Neoplasms; Smoking

In the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, alpha-tocopherol supplementation decreased prostate cancer incidence, whereas beta-carotene increased the risk of lung cancer and total mortality. Postintervention follow-up provides information regarding duration of the intervention effects and may reveal potential late effects of these antioxidants.. To analyze postintervention effects of alpha-tocopherol and beta-carotene on cancer incidence and total and cause-specific mortality.. Postintervention follow-up assessment of cancer incidence and cause-specific mortality (6 years [May 1, 1993-April 30, 1999]) and total mortality (8 years [May 1, 1993-April 30, 2001]) of 25 563 men. In the ATBC Study, 29 133 male smokers aged 50 to 69 years received alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5 to 8 years. End point information was obtained from the Finnish Cancer Registry and the Register of Causes of Death. Cancer cases were confirmed through medical record review.. Site-specific cancer incidence and total and cause-specific mortality and calendar time-specific risk for lung cancer incidence and total mortality.. Overall posttrial relative risk (RR) for lung cancer incidence (n = 1037) was 1.06 (95% confidence interval [CI], 0.94-1.20) among recipients of beta-carotene compared with nonrecipients. For prostate cancer incidence (n = 672), the RR was 0.88 (95% CI, 0.76-1.03) for participants receiving alpha-tocopherol compared with nonrecipients. No late preventive effects on other cancers were observed for either supplement. There were 7261 individuals who died by April 30, 2001, during the posttrial follow-up period; the RR was 1.01 (95% CI, 0.96-1.05) for alpha-tocopherol recipients vs nonrecipients and 1.07 (95% CI, 1.02-1.12) for beta-carotene recipients vs nonrecipients. Regarding duration of intervention effects and potential late effects, the excess risk for beta-carotene recipients was no longer evident 4 to 6 years after ending the intervention and was primarily due to cardiovascular diseases.. The beneficial and adverse effects of supplemental alpha-tocopherol and beta-carotene disappeared during postintervention follow-up. The preventive effects of alpha-tocopherol on prostate cancer require confirmation in other trials. Smokers should avoid beta-carotene supplementation.

Topics: Aged; alpha-Tocopherol; Antioxidants; beta Carotene; Cause of Death; Dietary Supplements; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prostatic Neoplasms; Risk; Smoking

High prediagnostic serum beta-cryptoxanthin levels have been found to be associated with reduced risk of lung cancer in a recent cohort study of Chinese men in Shanghai, China. Data on dietary beta-cryptoxanthin, and other specific carotenoids and antioxidants in relation to lung cancer, particularly in non-Western populations, are scarce. The aim of the present study was to assess the roles of dietary antioxidants in the development of lung cancer. Between April 1993 and December 1998, 63,257 Chinese men and women ages 45-74 years in Singapore participated in a prospective study of diet and cancer. At baseline, an in-person interview was conducted using a structured questionnaire for information on usual dietary habits, tobacco smoking, and other lifestyle factors. A Singapore food composition database was used to estimate intake of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein/zeaxanthin, vitamins A, C, and E, and folate in study subjects. During the first 8 years of follow-up, 482 lung cancer cases occurred among cohort members. High levels of dietary beta-cryptoxanthin were associated with reduced risk of lung cancer; relative to the lowest quintile, the self-reported smoking adjusted relative risks (95% confidence intervals) for the highest quintile were 0.73 (0.54-0.98) among all of the subjects and 0.63 (0.41-0.99) among current smokers. Before adjustment for cigarette smoking, dietary vitamin C was associated with a statistically significant reduction in risk of lung cancer. However the inverse vitamin C-lung cancer association was largely explained by smoking and dietary beta-cryptoxanthin. Other carotenoids (alpha-carotene, beta-carotene, lycopene, and lutein/zeaxanthin), vitamins A and E, and folate were not associated significantly with lung cancer risk after adjustment for cigarette smoking. We recognized that potential measurement errors in cigarette smoking may exert an effect on the dietary beta-cryptoxanthin-lung cancer association. After additional adjustments were made for the residual confounding by smoking using statistical models, about 15-40% reduction in risk of lung cancer was seen for subjects in the highest versus lowest 10th percentile of dietary beta-cryptoxanthin. The present study lends additional credence to prior experimental and epidemiological data in support of the hypothesis that dietary beta-cryptoxanthin is a chemopreventive agent for lung cancer in humans.

Topics: Aged; Antioxidants; beta Carotene; China; Cohort Studies; Cryptoxanthins; Diet; Feeding Behavior; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Registries; Risk Factors; Singapore; Smoking; Surveys and Questionnaires; Xanthophylls

In addition to its antioxidant activity, beta-carotene (BC) is known to enhance gap junction intercellular communication (GJIC) by up-regulation of connexin 43 (Cx43), an action that may be important in its control of tumor growth. Surprisingly, two clinical trials on supplemental BC suggest that BC may increase lung cancer incidence in smokers. Recently, an animal study indicated that a very high dose of BC (50 mg/kg b.w./day for 5 days) decreases GJIC in rat liver, while a lower dose (5 mg/kg b.w./day) increases GJIC. It is unclear how high-doses of BC inhibit GJIC. In this study, we tested whether oxidized BC (OBC, obtained by heating BC at 60 degrees C in open air for 1 h) may inhibit GJIC. We incubated a human lung cancer cell line (A549) with OBC or BC at 2-10 microM for 5 days. Cell viability (by Trypan-blue assay), GJIC (by scrape-loading dye transfer) and Cx43 expression (by western blotting and immunocytochemical localization) were measured to investigate the effects of OBC and BC on GJIC and the possible mechanisms. The results show that OBC at concentrations lower than 10 microM did not significantly affect cell viability. However, OBC at 5 muM inhibited GJIC, whereas BC at 5 microM markedly increased GJIC. The loss of GJIC in A549 induced by OBC accompanied the aberrant localization and phosphorylation of connexin43 (Cx43). These changes in the expression of Cx43 induced by OBC were similar to those induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter. Thus, our results suggest that in vivo inhibition of GJIC by a high dose of BC on GJIC is, at least in part, attributable to the effect of OBC.

Topics: Adenocarcinoma; Antioxidants; beta Carotene; Blotting, Western; Cell Communication; Cell Line, Tumor; Connexin 43; Fluorescent Dyes; Gap Junctions; Humans; Immunohistochemistry; Indicators and Reagents; Isoquinolines; Lung Neoplasms; Oxidation-Reduction; Phosphorylation

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Biological Evolution; Carcinogens; Carotenoids; Disease Models, Animal; Humans; Lung Neoplasms; Lycopene; Male; Prostatic Neoplasms; Rats; Solanum lycopersicum

The aim of this investigation was to study the effects of fat-soluble extracts from vegetable powder (FEFVP) and beta-carotene on the proliferation and apoptosis of cultured YTMLC-90 lung cancer cells.. The lung cancer cells were continuously exposed to a broad range of concentration of FEFVP and beta-carotene. The proliferation was evaluated in MTT test. The induction of apoptosis was evaluated by morphological change, DNA fragmentation analysis, and DNA content analysis combined with flow cytometric analysis.. Both FEFVP and beta-carotene were found to inhibit cell proliferation and to induce morphologic changes consistent with apoptosis in YTMLC-90 cancer cells, including cellular shrinkage, chromatin condensation and nuclear fragmentation. DNA agarose gel electrophoresis showed DNA fragmentation 'ladder'. Flow cytometric analysis revealed decreased DNA content and the presence of a sub-G1 apoptotic peak.. These findings are consistent with the induction of apoptosis. Moreover, the effects of FEFVP are stronger than those of beta-carotene. FEFVP inhibits the growth of YTMLC-90 probably via the induction of apoptosis cancer cells.

Topics: Antioxidants; Apoptosis; beta Carotene; Cell Division; DNA Damage; Flow Cytometry; Humans; Lung Neoplasms; Plant Extracts; Powders; Tumor Cells, Cultured; Vegetables

The structures of two novel 3,4-seco-lanostane-type triterpenes isolated from the sclerotium of Poria cocos were established to be 16alpha-hydroxy-3,4-seco-lanosta-4(28),8,24-triene-3,21-dioic acid (1; poricoic acid G) and 16alpha-hydroxy-3,4-seco-24-methyllanosta-4(28),8,24(24(1))-triene-3,21-dioic acid (2; poricoic acid H) on the basis of spectroscopic methods. These two, and eight other known compounds isolated from the sclerotium, poricoic acid B (3), poricoic acid A (4), tumulosic acid (5), dehydrotumulosic acid (6), 3-epidehydrotumulosic acid (7), polyporenic acid C (8), 25-hydroxy-3-epidehydrotumulosic acid (9), and dehydroabietic acid methyl ester (10), showed potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Evaluation of the cytotoxicity of compounds 1 and 4 against human cancer cell lines revealed that 1 was significantly cytotoxic to leukemia HL-60 cells [GI(50) (concentration that yields 50% growth) value 39.3 nM], although it showed only moderate cytotoxicity to the other cells. Compound 4 exhibited moderate cytotoxicity to all of the cancer cell lines tested.

Topics: Antineoplastic Agents, Phytogenic; Brain Neoplasms; Chromatography, High Pressure Liquid; Colonic Neoplasms; Drug Screening Assays, Antitumor; Female; Humans; Japan; Kidney Neoplasms; Lanosterol; Leukemia, Myeloid; Lung Neoplasms; Melanoma; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Ovarian Neoplasms; Plants, Medicinal; Polyporaceae; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Triterpenes; Tumor Cells, Cultured

The induction of pre-cancerous squamous metaplasia in lungs of ferrets by high doses of dietary beta-carotene (BC) and cigarette smoke is compared with and contrasted to the different effects of high doses of dietary BC on skin papilloma and carcinoma induction by the two-stage carcinogenesis protocol. Whereas high dietary BC can inhibit the conversion of skin papillomas to carcinomas, such treatment would not be expected to inhibit smoke-induced lung tumors.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; beta Carotene; Carcinogens; Dose-Response Relationship, Drug; Ferrets; Lung Neoplasms; Mice; Nicotiana; Papilloma; Precancerous Conditions; Skin Neoplasms; Smoke; Tetradecanoylphorbol Acetate

In human clinical trials it was found that the putative chemopreventive agent beta-carotene not only failed to protect active smokers against the carcinogenic action of tobacco smoke, but actually increased their risk of developing lung cancer. In preclinical animal studies, beta-carotene had been effective against some chemically induced cancers, but not against tumors in the respiratory tract. We exposed male strain A/J mice to tobacco smoke at a concentration of 140 mg/m(3) of total suspended particulate matter, 6 h a day, 5 days a week, for either 4 or 5 months, followed by a recovery period in air for 4 or 5 months, or for 9 months without recovery period. beta-carotene was added in the form of gelatin beadlets to the AIN-93G diet either during or following tobacco smoke exposure at concentrations of 0.005, 0.05 and 0.5%. In the supplement-fed animals, plasma and lung levels of beta-carotene were higher than they were in animals fed control diets. Exposure to tobacco smoke increased rather than decreased plasma beta-carotene levels, but had no significant effect on lung levels. After 9 months, lung tumor multiplicities and incidence were determined. Tobacco smoke increased both lung tumor multiplicities and incidences, but beta-carotene failed to modulate tumor development under all exposure conditions. Animal studies in a model of tobacco smoke carcinogenesis would thus have predicted the absence of any beneficial effects of beta-carotene supplementation in current or former smokers, but would have failed to anticipate the increase in lung cancer risk.

Topics: Animals; Antioxidants; Atmosphere Exposure Chambers; beta Carotene; Chromatography, High Pressure Liquid; Diet; Lung Neoplasms; Male; Mice; Mice, Inbred A; Nicotiana; Smoke

Findings from several beta-carotene supplementation trials were unexpected and conflicted with most observational studies. Carotenoids other than beta-carotene are found in a variety of fruits and vegetables and may play a role in this important malignancy, but previous findings regarding the five major carotenoids are inconsistent. The authors analyzed the associations between dietary beta-carotene, beta-carotene, lutein/zeaxanthin, lycopene, beta-cryptoxanthin, vitamin A, serum beta-carotene, and serum retinol and the lung cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of male smokers conducted in southwestern Finland between 1985 and 1993. Of the 27,084 male smokers aged 50-69 years who completed the 276-food item dietary questionnaire at baseline, 1,644 developed lung cancer during up to 14 years of follow-up. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals. Consumption of fruits and vegetables was associated with a lower lung cancer risk (relative risk = 0.73, 95% confidence interval: 0.62, 0.86, highest vs. lowest quintile). Lower risks of lung cancer were observed for the highest versus the lowest quintiles of lycopene (28%), lutein/zeaxanthin (17%), beta-cryptoxanthin (15%), total carotenoids (16%), serum beta-carotene (19%), and serum retinol (27%). These findings suggest that high fruit and vegetable consumption, particularly a diet rich in carotenoids, tomatoes, and tomato-based products, may reduce the risk of lung cancer.

Topics: Aged; alpha-Tocopherol; Antioxidants; beta Carotene; Carotenoids; Cohort Studies; Diet; Fruit; Humans; Lung Neoplasms; Male; Middle Aged; Risk Factors; Smoking; Vegetables; Vitamin A

The effect of beta-carotene on the morphology of NCI-H69 small cell lung cancer cells that had undergone beta-carotene-induced growth reduction (P < 0.05) was examined. The cells were grown at 1 x 10(8) cells/L and were cultured with or without 20 micromol/L beta-carotene. The qualitative electron microscopic observations revealed that beta-carotene-treated cells contained more vacuoles than control cells not treated with beta-carotene. The quantitative image analysis showed a significantly smaller (P < 0.05) value of the nuclear roundness factor for treated cells compared with control cells, indicating an irregular nuclear morphology of beta-carotene-treated cells. The major diameter of the cells and the minor diameter of the nuclei were significantly smaller (P < 0.05), and the nuclear perimeter was significantly larger (P < 0.05) in beta-carotene-treated cells. The ratio of nucleus to cytoplasm was significantly less (P < 0.05) in beta-carotene-treated cells compared with control cells, indicating a less malignant growth of the cells. These results demonstrate that the treatment of small cell lung cancer cells with beta-carotene induces morphological changes in the cells concomitant with a reduction in their proliferation. Further investigation is required to show a direct effect of beta-carotene or its intracellular polar metabolites on the morphology of these cells.

Topics: Antioxidants; beta Carotene; Carcinoma, Small Cell; Cell Division; Humans; Image Processing, Computer-Assisted; Lung Neoplasms; Microscopy, Electron; Tumor Cells, Cultured; Vacuoles

The results of three randomized trials of beta-carotene supplementation for the prevention of lung cancer among smokers are in contradiction to a large body of epidemiologic evidence for the reduction of risk of lung cancer among smokers with higher intake and/or higher serum levels of beta-carotene. Complicating this issue are widely noted negative associations between tobacco use and intake or serum levels of beta-carotene. Although observational studies attempt to control for reported smoking histories, the accuracy of self-reported smoking is uncertain; correlations as low as 0.5 between reported and true smoking exposure are not inconsistent with studies of biomarkers of cigarette exposure. The authors developed a simple statistical model for random errors in reported smoking (relative to true tobacco exposure) and assumed a modest (inverse) relation between true tobacco exposure and serum beta-carotene. Calculations from this model, combined with a model for lung cancer contemplated by Doll and Peto (J Epidemiol Community Health 1978;78:303-13), suggest that biases in assessment of smoking exposure between smokers with low versus high beta-carotene intake may plausibly explain much or all of the observed protective effect of high beta-carotene levels. Appropriate cohort studies of lung cancer in smokers, utilizing biomarkers of smoking, are needed and are presently ongoing.

Topics: Antioxidants; beta Carotene; Confounding Factors, Epidemiologic; Epidemiologic Studies; Humans; Lung Neoplasms; Models, Statistical; Smoking

Topics: Antioxidants; beta Carotene; Free Radical Scavengers; Fruit; Humans; Lung Neoplasms; Neoplasms; Smoking; Vegetables

Topics: alpha-Tocopherol; Animals; beta Carotene; Cell Division; Chemoprevention; Humans; Lung Neoplasms; Prognosis; Receptors, Retinoic Acid; Smoking; Tretinoin

Topics: Animals; Animals, Laboratory; beta Carotene; Carcinogens; Disease Models, Animal; Ferrets; Liver Neoplasms; Lung Neoplasms; Marmota; Mice; Mutation; Neoplasms; Phenotype; Sciuridae; Skin Neoplasms; Zebrafish

Topics: beta Carotene; Carcinoma, Bronchogenic; Cocarcinogenesis; Humans; Lung Neoplasms; Smoking

The purpose of this study is to examine the carotenoid effects on lung tumorigenesis induced by intratracheal instillation of diesel exhaust particles (DEP) into mice weekly for 20 wk. It was suggested that active oxygen radicals might play an important role in DEP-induced lung tumorigenesis. Mice were divided to 4 groups of diet containing 0.02% of palm oil carotene, 0.02% of beta-carotene, or no carotenoid with or without DEP. The BF group (4% fat) and the HF group (16% fat) were prepared for each diet group. The experimental period was 12 mo. By the administration of palm oil carotene, neither adenocarcinoma nor adenoma was found in the BF group. In the HF group with palm oil carotene, no adenocarcinoma was observed, and adenoma was reduced. Adenoma in the HF group was not greatly reduced by beta-carotene, but rather increased in the BF group. No adenocarcinoma was found in either the BF or the HF groups with beta-carotene. The 8-hydroxydeoxyguanosine/deoxyguanosine ratio in palm carotene groups was lower than in the other groups, while that in beta-carotene groups was not. From these results, palm oil carotene was suggested to prevent lung tumorigenesis by its protective effect on DNA from active oxygen. Beta-carotene was supposed to have different effects from palm oil carotene on lung tumorigenesis. Besides the chemopreventive effect, the growth of mice was inhibited by the administration of palm oil carotene. Further studies are necessary to elucidate the mechanisms of carotenoid effects.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenocarcinoma; Adenoma; Animals; Antioxidants; beta Carotene; Carotenoids; Deoxyguanosine; Dietary Fats; DNA Damage; Growth; Lung; Lung Neoplasms; Male; Mice; Mice, Inbred ICR; Reactive Oxygen Species; Time Factors; Vehicle Emissions; Vitamins

Higher blood levels of beta-carotene have been found to be associated with reduced risk of lung cancer, but large intervention trials have failed to demonstrate reduced lung cancer incidence after prolonged high-dose beta-carotene supplementation. Data on blood levels of specific carotenoids other than beta-carotene in relation to lung cancer are scarce. Little is known about the relationship between prediagnostic serum levels of carotenoids, retinol, and tocopherols, and risk of lung cancer especially in non-Western populations. Between January 1986 and September 1989, 18,244 men ages 45-64 years participated in a prospective study of diet and cancer in Shanghai, China. Information on tobacco smoking and other lifestyle factors was obtained through in-person interviews. A serum sample was collected from each study participant at baseline. During the first 12 years of follow-up, 209 lung cancer cases, excluding those diagnosed within 2 years of enrollment, were identified. For each cancer case, three cancer-free control subjects were randomly selected from the cohort and matched to the index case by age (within 2 years), month and year of blood sample collection, and neighborhood of residence. Serum concentrations of retinol, alpha- and gamma-tocopherols, and specific carotenoids including alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin were determined on the 209 cases and 622 matched controls by high-performance liquid chromatography methods. A high prediagnostic serum level of beta-cryptoxanthin was significantly associated with reduced risk of lung cancer; relative to the lowest quartile, the smoking-adjusted relative risks (95% confidence intervals) for the 2nd, 3rd, and 4th quartile categories were 0.72 (0.41-1.26), 0.42 (0.21-0.84), and 0.45 (0.22-0.92), respectively (P for trend = 0.02). Increased serum levels of other specific carotenoids including alpha-carotene, beta-carotene, lycopene, and lutein/zeaxanthin were related to reduced risk of lung cancer although the inverse associations were no longer statistically significant after adjustment for smoking. A statistically significant 37% reduction in risk of lung cancer was noted in smokers with above versus below median level of total carotenoids. Serum retinol levels showed a threshold effect on lung cancer risk. Compared with the lowest quartile (<40 microg/dl), the smoking-adjusted relative risk (95% confidence interval) was 0.60 (0.39-0.92) for men in the 2n

Topics: Aged; beta Carotene; Carotenoids; Case-Control Studies; China; Cryptoxanthins; Humans; Lung Neoplasms; Male; Middle Aged; Predictive Value of Tests; Risk Factors; Smoking; Vitamin A; Xanthophylls

Topics: Anticarcinogenic Agents; Asbestos; beta Carotene; Carcinogens; Clinical Trials as Topic; Evidence-Based Medicine; Humans; Incidence; Lung Neoplasms; Occupational Exposure; Risk Factors; Smoking; United States

We evaluated the association between exposure to environmental tobacco smoke (ETS) from husbands who smoke and plasma levels of antioxidant vitamins among nonsmoking women. A total of 1249 women from four areas in Italy answered a self-administered questionnaire, reported their diets on a food frequency questionnaire, had a medical examination, and gave their blood for alpha and beta-carotene, retinol, L-ascorbic acid, alpha-tocopherol, and lycopene determinations. Urinary cotinine was used to evaluate the level of recent exposure to ETS. After adjusting for study center, age and education, we found no association between ETS exposure and daily nutrient intake of beta-carotene, retinol, L-ascorbic acid, and alpha-tocopherol. However, we found an inverse dose-response relationship between intensity of current husband's smoke and concentrations of plasma beta-carotene and L-ascorbic acid. The associations remained even after controlling for daily beta-carotene and vitamin C intake and for other potential confounders (vitamin supplementation, alcohol consumption, and body mass index). Moreover, when urinary cotinine was considered as the exposure variable, a significant inverse association with plasma beta-carotene was found. The findings may be of interest to explain the biological mechanism that link ETS exposure with lung cancer and ischemic heart diseases.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Cross-Sectional Studies; Environmental Exposure; Female; Humans; Lung Neoplasms; Male; Middle Aged; Myocardial Ischemia; Spouses; Tobacco Smoke Pollution

Previously we reported that a commercial Satsuma mandarin (Citrus unshiu Marc.) juice (MJ), MJ2 and MJ5, especially MJ5, effectively suppressed chemically-induced rat colon carcinogenesis (Int. J. Cancer 88 (2000) 146). MJ2 and MJ5 prepared from MJ have higher amounts of beta-cryptoxanthin and hesperidin than MJ, suggesting that principle chemopreventive factors in MJs may be beta-cryptoxanthin and hesperidin. Present study was conducted to test whether these MJs could modify carcinogenesis in other organ, lung initiated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in male A/J mice. Mice were given an intraperitoneal injection of NNK (10 micromol in saline/mouse) to induce pulmonary neoplasms. They also received MJ, MJ2 or MJ5 as a drinking water at night for 21 weeks, starting 1 week after the NNK injection. Treatments with MJ, MJ2, and MJ5 reduced the incidence of lung tumors and the inhibition by MJ5 (29% reduction) was statistically significant (P<0.05). MJs treatment lowered the multiplicity of lung neoplasms without statistical significance. Immunohistochemically, MJs, especially MJ5, reduced proliferating cell nuclear antigen (PCNA)-positive index in the lung tumors without affecting PCNA index in hyperplastic alveolar cell lesions. These findings might suggest that MJ5, which contain 3.9 mg beta-cryptoxanthin and 100 mg hesperidin in 100 g sample), has chemopreventive ability against NNK-induced mouse lung tumorigenesis.

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Beverages; Carcinogens; Citrus; Cryptoxanthins; Hesperidin; Immunoenzyme Techniques; Incidence; Injections, Intraperitoneal; Lung Neoplasms; Male; Mice; Mice, Inbred A; Nitrosamines; Nucleolus Organizer Region; Proliferating Cell Nuclear Antigen; Xanthophylls

We have examined the role of dietary patterns and specific dietary nutrients in the etiology of lung cancer among non-smokers using a multicenter case-control study.. 506 non-smoking incident lung cancer cases were identified in the eight centers along with 1045 non-smoking controls. Dietary habits were assessed using a quantitative food-frequency questionnaire administered by personal interview. Based on this information, measures of total carotenoids, beta-carotene and retinol nutrient intake were estimated.. Protective effects against lung cancer were observed for high consumption of tomatoes, (odds ratio (OR) = 0.5; 95% confidence interval (CI) 0.4-0.6), lettuce (OR = 0.6; 95% CI 0.3-1.2), carrots (OR = 0.8; 95% CI 0.5-1.1), margarine (OR = 0.7; 95% CI 0.5-0.8) and cheese (OR = 0.7; 95% CI 0.5-1.0). Only weak protective effects were observed for high consumption of all carotenoids (OR = 0.8; 95% CI 0.6-1.0), beta-carotene (OR = 0.8; 95% CI 0.6-1.1) and retinol (OR = 0.9; 95% CI 0.7-1.1). Protective effects for high levels of fruit consumption were restricted to squamous cell carcinoma (OR = 0.7; 95% CI 0.4-1.2) and small cell carcinoma (OR = 0.7; 95% CI 0.4-1.2), and were not apparent for adenocarcinoma (OR = 0.9; 95% CI 0.6-1.3). Similarly, any excess risk associated with meat, butter and egg consumption was restricted to squamous and small cell carcinomas, but was not detected for adenocarcinomas.. This evidence suggests that the public health significance of increasing vegetable consumption among the bottom third of the population would include a reduction in the incidence of lung cancer among lifetime non-smokers by at least 25%, and possibly more. A similar protective effect for increased fruit consumption may be present for squamous cell and small cell lung carcinomas.

Topics: Adenocarcinoma; Adult; Aged; beta Carotene; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; Diet; Female; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Public Health; Smoking; Vegetables; Vitamin A

Topics: beta Carotene; Carotenoids; Case-Control Studies; Cheese; Diet; Europe; Fruit; Humans; Lung Neoplasms; Odds Ratio; Risk Factors; Tobacco Smoke Pollution; Vegetables; Vitamin A

Topics: Anticarcinogenic Agents; beta Carotene; Breast Neoplasms; Clinical Trials as Topic; Female; Humans; Lung Neoplasms; Neoplasms; Tamoxifen; Treatment Outcome; Uterine Cervical Neoplasms

Topics: Acetylcysteine; Anticarcinogenic Agents; beta Carotene; Carcinogens; Diterpenes; Glucuronides; Glutathione; Humans; Lung Neoplasms; Randomized Controlled Trials as Topic; Retinyl Esters; Vitamin A

Topics: Anticarcinogenic Agents; Antioxidants; beta Carotene; Environmental Exposure; Humans; Lung Neoplasms; Nitrogen Dioxide; Oxidative Stress; Oxygenases; Ozone; Risk Factors

Carotenoids may reduce lung carcinogenesis because of their antioxidant properties; however, few studies have examined the relation between intakes of individual carotenoids and lung cancer risk.. The aim of this study was to examine the relation between lung cancer risk and intakes of alpha-carotene, beta-carotene, lutein, lycopene, and beta-cryptoxanthin in 2 large cohorts.. During a 10-y follow-up period, 275 new cases of lung cancer were diagnosed in 46924 men; during a 12-y follow-up period, 519 new cases were diagnosed in 77283 women. Carotenoid intakes were derived from the reported consumption of fruit and vegetables on food-frequency questionnaires administered at baseline and during follow-up. The data were analyzed separately for each cohort and the results were pooled to compute overall relative risks (RRs).. In the pooled analyses, alpha-carotene and lycopene intakes were significantly associated with a lower risk of lung cancer; the association with beta-carotene, lutein, and beta-cryptoxanthin intakes were inverse but not significant. Lung cancer risk was significantly lower in subjects who consumed a diet high in a variety of carotenoids (RR: 0.68; 95% CI: 0.49, 0.94 for highest compared with lowest total carotenoid score category). Inverse associations were strongest after a 4-8-y lag between dietary assessment and date of diagnosis. In subjects who never smoked, a 63% lower incidence of lung cancer was observed for the top compared with the bottom quintile of alpha-carotene intake (RR: 0.37; 95% CI: 0.18, 0.77).. Data from 2 cohort studies suggest that several carotenoids may reduce the risk of lung cancer.

Topics: Adult; Aged; beta Carotene; Carotenoids; Cohort Studies; Cryptoxanthins; Eating; Female; Humans; Linear Models; Lung Neoplasms; Lutein; Lycopene; Male; Middle Aged; Prospective Studies; Regression Analysis; Risk Factors; Smoking; Surveys and Questionnaires; Xanthophylls

Human cellular glutathione peroxidase 1 (hGPX1) is a selenium-dependent enzyme that participates in the detoxification of hydrogen peroxide and a wide range of organic peroxides. We conducted a case-control study nested within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study cohort to evaluate the association between the proline to leucine polymorphism at codon 198 of hGPX1 and lung cancer risk. Cases (n = 315) were matched to controls on age (+/-5 years), intervention group, and study clinic using incidence density sampling in a 1:1 ratio. The prevalence of the hGPX1 Pro198Leu variant allele was 58% for controls and 71% for cases (P < 0.001). Using conditional logistic regression, we found a significant association between hGPX1 genotype and lung cancer risk. The odds ratio for heterozygotes was 1.8 (95% confidence interval, 1.2-2.8) and 2.3 (95% confidence interval, 1.3-3.8) for homozygous variants compared to wild-type individuals. Due to its high prevalence, the hGPX1 variant may contribute significantly to lung cancer risk among Caucasians but not among ethnic Chinese who do not exhibit this polymorphism.

Topics: Age Factors; Aged; Antioxidants; beta Carotene; Case-Control Studies; Codon; Genotype; Germ-Line Mutation; Glutathione Peroxidase; Glutathione Peroxidase GPX1; Humans; Lung Neoplasms; Male; Middle Aged; Polymorphism, Genetic; Risk Factors; Smoking; Vitamin E

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Asbestosis; beta Carotene; Cocarcinogenesis; Cohort Studies; Down-Regulation; Ferrets; Gene Expression Regulation; Genes, fos; Genes, jun; Humans; Incidence; Lung; Lung Neoplasms; Metaplasia; Nicotiana; Plants, Toxic; Proliferating Cell Nuclear Antigen; Receptors, Retinoic Acid; Smoke; Smoking; Transcription Factor AP-1; Tretinoin

Epidemiologic studies have demonstrated that individuals who eat more fruits and vegetables and/or have high levels of serum beta-carotene have a lower risk of cancer, especially lung cancer. However, recent human intervention studies using beta-carotene supplements have shown an increase in the risk of lung cancer among smokers and asbestos workers. In this study, we used an animal model system to evaluate the hazard associated with a combination of high-dose beta-carotene supplementation and tobacco smoking.. Ferrets were given a beta-carotene supplement, exposed to cigarette smoke, or both for 6 months. Cell proliferation and squamous metaplasia in lung tissue were assessed by examination of proliferating-cell nuclear antigen expression and histopathologic examination, respectively. beta-Carotene and retinoid concentrations in lung tissue and plasma samples were analyzed by high-performance liquid chromatography. Expression of genes for retinoic acid receptors (RARs) and activator protein-1 (encoded by the c-Jun and c-Fos genes) in lung tissue specimens was examined by western blotting.. A strong proliferative response in lung tissue and squamous metaplasia was observed in all beta-carotene-supplemented animals, and this response was enhanced by exposure to tobacco smoke. When compared with control groups, all three treatment groups had statistically significantly lower concentrations of retinoic acid in lung tissue, and they exhibited 18%-73% reductions in RARbeta gene expression; however, RARalpha and RARgamma gene expression was not reduced. Ferrets given a beta-carotene supplement and exposed to tobacco smoke had threefold to fourfold elevated expression of the c-Jun and c-Fos genes.. Diminished retinoid signaling, resulting from the suppression of RARbeta gene expression and overexpression of activator protein-1, could be a mechanism to enhance lung tumorigenesis after high-dose beta-carotene supplementation and exposure to tobacco smoke.

Topics: Animals; beta Carotene; Cell Division; Cocarcinogenesis; Diterpenes; Down-Regulation; Environmental Exposure; Ferrets; Gene Expression Regulation; Genes, fos; Genes, jun; Humans; Lung; Lung Neoplasms; Male; Metaplasia; Nicotiana; Plants, Toxic; Precancerous Conditions; Proliferating Cell Nuclear Antigen; Receptors, Retinoic Acid; Retinyl Esters; Signal Transduction; Smoke; Transcription Factor AP-1; Tretinoin; Vitamin A

Topics: 3T3 Cells; Animals; beta Carotene; Carcinogens; Cocarcinogenesis; Cytochrome P-450 Enzyme System; Enzyme Induction; Humans; Lung; Lung Neoplasms; Male; Mice; Rats; Rats, Sprague-Dawley; Smoking; Superoxides

Recent intervention trials reported that smokers given dietary beta-carotene supplementation exhibited an increased risk of lung cancer and overall mortality. beta-Carotene has been hypothesized to promote lung carcinogenesis by acting as a prooxidant in the smoke-exposed lung. We have examined the interactions of cigarette smoke with beta-carotene in model systems. Both whole smoke and gas-phase smoke oxidized beta-carotene in toluene to several products, including carbonyl-containing polyene chain cleavage products and beta-carotene epoxides. A major product of the reaction was identified as 4-nitro-beta-carotene, which was formed by nitrogen oxides in smoke. Both cis and all-trans isomers of 4-nitro-beta-carotene were detected. The hypothesis that smoke-driven beta-carotene autoxidation exerts prooxidant effects was tested in a liposome system. Lipid peroxidation in dilinoleoylphosphatidylcholine liposomes exposed to gas-phase smoke was modestly inhibited by the incorporation of 0.1 mol % beta-carotene. Both the lipid soluble antioxidant alpha-tocopherol and the water soluble antioxidant ascorbate were oxidized more slowly by gas-phase smoke exposure in liposomes containing beta-carotene. These data indicate that beta-carotene exerts weak antioxidant effects against smoke-induced oxidative damage in vitro. It is unlikely that a prooxidant effect of beta-carotene occurs under biologically relevant conditions or is responsible for an increased incidence of lung cancer observed in smokers who consume beta-carotene supplements.

Topics: Animals; Antioxidants; beta Carotene; Carotenoids; Cattle; Dietary Supplements; Evaluation Studies as Topic; Humans; Liposomes; Lung Neoplasms; Oxidants; Oxidation-Reduction; Risk Factors; Smoking; Structure-Activity Relationship; Toluene

Delivery of beta-carotene in tetrahydrofuran slowed the growth of NCI-H69 small cell lung cancer cells. Analysis of cells and cellular fractions revealed that beta-carotene-treated cells accumulated beta-carotene as well as some polar metabolites, primarily in the crude nuclei. Cells were grown at 1 x 10(5) cells/ml and treated with 20 microM beta-carotene. Growth monitoring up to 15 days indicated an inverse relationship between the duration of beta-carotene treatment and the rate of cell growth. Reverse-phase high-performance liquid chromatography analysis of treated cells showed the presence of beta-carotene, retinoic acid, retinol, and retinal, with beta-carotene accounting for the major material recovered. When cellular fractions were analyzed for beta-carotene, it was found to be located primarily in the crude nuclei. These results demonstrate that treatment of small cell lung cancer cells with beta-carotene results in a reduced growth of the cells. Further investigation is required to show a direct effect of beta-carotene or its intracellular polar metabolites on these cells. Accumulation of beta-carotene in the nucleus suggests a need for evaluating the nuclear role for beta-carotene.

Topics: Antioxidants; beta Carotene; Carcinoma, Small Cell; Cell Division; Cells, Cultured; Humans; Lung Neoplasms; Retinaldehyde; Tretinoin; Tumor Cells, Cultured; Vitamin A

To examine the protective role of dietary antioxidants (carotenoids, vitamin C, vitamin E, glutathione, and flavonoids) in lung cancer risk, a case-control study involving 541 cases of lung cancer and 540 hospitalized controls was carried out in Uruguay. The relevant variables were energy adjusted using the residuals method and then categorized in quartiles. Adjusted odds ratios (ORs) for antioxidants were calculated through unconditional logistic regression. With the exception of lycopene and vitamin C, the remaining antioxidants were associated with significant reductions in risk of lung cancer. Of particular interest was the inverse association between dietary glutathione and lung cancer [OR of quartile with highest intake compared with lowest quartile = 0.42, 95% confidence interval (CI) = 0.27-0.63]. Also, carotenoids and vitamin E were associated with significant reductions in risk of lung cancer (OR = 0.43, 95% CI = 0.29-0.64 for total carotenoids and OR = 0.50, 95% CI = 0.39-0.85 for vitamin E). A joint effect for high vs. low intakes of beta-carotene and glutathione was associated with a significant reduction in risk (OR = 0.32, 95% CI = 0.22-0.46). It could be concluded that dietary antioxidants are associated with a significant protective effect in lung carcinogenesis and that the inverse association for glutathione persisted after controlling for total vegetables and fruits.

Topics: Adenocarcinoma; Adult; Age Distribution; Aged; Aged, 80 and over; Antioxidants; beta Carotene; Carcinoma; Carcinoma, Large Cell; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Case-Control Studies; Diet; Glutathione; Humans; Logistic Models; Lung Neoplasms; Male; Middle Aged; Odds Ratio; Risk Factors; Surveys and Questionnaires; Uruguay

We evaluated the association between alcohol intake and lung cancer in a trial-based cohort in Finland, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study).. During an average of 7.7 years of follow-up, 1059 lung cancer cases were diagnosed among the 27,111 male smokers with complete alcohol and dietary information. The relationship between alcohol and lung cancer was assessed in multivariate Cox regression models that adjusted for age, smoking, body mass index and intervention group.. Nondrinkers, 11% of the study population, were at increased lung cancer risk compared to drinkers (RR = 1.2, 95% CI: 1.0-1.4), possibly due to the inclusion of ex-drinkers who had stopped drinking for health reasons. Among drinkers only, we observed no association between lung cancer and total ethanol or specific beverage (beer, wine, spirits) intake. We found no significant effect modification by level of smoking, dietary micronutrients or trial intervention group; however, for men in the highest quartile of alcohol intake, we observed a slight increase in risk for lighter smokers (<1 pack/day) and reduced risk among the heaviest smokers (>30 cigarettes/day).. We concluded that alcohol consumption was not a risk factor for lung cancer among male cigarette smokers, and its effect was not significantly modified by other factors, notably smoking history.

Topics: Aged; Alcohol Drinking; beta Carotene; Cohort Studies; Finland; Humans; Lung Neoplasms; Male; Middle Aged; Risk Assessment; Smoking; Vitamin E

Different methods for estimating the effect of treatment actually received in a longitudinal placebo-controlled trial with non-compliance are discussed. Total mortality from the ATBC Study is used as an illustrative example. In the ATBC Study some 25 per cent of the participants dropped out from active follow-up prior to the scheduled end of the study. The 'intention-to-treat' analysis showed an increased death risk in the beta-carotene arm when compared with the no beta-carotene arm. Owing to considerable non-compliance it is also of interest to estimate the effect of beta-carotene actually received. We use a simple model for the treatment action and discuss three methods for estimation of the treatment effect under the model - the 'intention-to-treat' approach, the 'as-treated' approach and the g-estimation approach. These approaches are compared in a simulation study under different settings for non-compliance. Finally, the data from the ATBC Study are analysed using the proposed methods.

Topics: beta Carotene; Computer Simulation; Finland; Humans; Lung Neoplasms; Male; Middle Aged; Models, Biological; Patient Dropouts; Proportional Hazards Models; Randomized Controlled Trials as Topic; Smoking; Treatment Refusal; Vitamin E

Topics: Adult; beta Carotene; Clinical Trials as Topic; Diet; Fruit; Humans; Lung Neoplasms; Risk Factors; Vegetables; Vitamin A Deficiency

Four agents, fumaric acid (FA), N-acetylcysteine (NAC), N-(4-hydroxyphenyl) retinamide (4-HPR) and beta-carotene (beta-CT), were evaluated for potential chemopreventive activity using the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor model in female A/J mice. The agents were evaluated in both 16-week and 52-week bioassays at two dose levels corresponding to 0.8 maximum tolerated dose (MTD) and 0.4 MTD administered throughout the bioassay either in the diet (FA, 160 and 80 mmol/kg diet; NAC, 160 and 80 mmol/kg diet; 4-HPR, 4 and 2 mmol/kg diet) or by subcutaneous injection twice a week (beta-CT, 32 and 16 mg/kg b.w.). Mice were treated with a single i.p. dose of 10 micromol NNK in saline 1 week after administration of test agent. Lung adenomas were evaluated in the 16-week bioassay, whereas both adenomas and adenocarcinomas of the lung were determined in the 52-week bioassay. Both bioassays showed that all four agents did not significantly inhibit the total tumor incidence and multiplicity of the lung. However, the incidence of adenocarcinomas was reduced (P < 0.01) at 52 weeks in NNK groups given either 0.8 MTD NAC or 0.8 MTD beta-CT compared with the NNK control group. The decreases in adenocarcinomas were accompanied by corresponding increases in adenomas in these treatment groups. Thus, this study showed that FA, NAC, 4-HPR and beta-CT did not inhibit the total tumor formation, however, at the higher doses both NAC and beta-CT significantly retarded the malignant progression in the lung of NNK-treated A/J mice.

Topics: Acetylcysteine; Animals; Anticarcinogenic Agents; beta Carotene; Carcinogens; Dose-Response Relationship, Drug; Female; Fenretinide; Fumarates; Lung Neoplasms; Mice; Mice, Inbred A; Nicotiana; Nitrosamines; Plants, Toxic

The inhibitory effects of the newly-developed forms of beta-carotene--water-soluble and liposomal--have been studied in rats and mice bearing tumors induced in 4 models of carcinogenesis. Mammary tumors were induced by single injections of 1 mg methylnitrosourea into each gland. Esophageal tumors were induced in male rats by intragastric administration of 3 mg/kg methylbenzylnitrosoamine, thrice a week for 4 weeks. Tumors of the vagina and cervix uteri were induced by intravaginal painting with 25 mkg dimethylbenz(a)anthracene, twice a week for 6 weeks. Tumors of the lung were induced in female mice by intraperitoneal injection of 1 g/kg urethane, once a week for 6 weeks. With models I-III, animals received water-soluble beta-carotene (Aquiton-10) with drinking water (200 mg/I), on completion of carcinogen treatment and for another 9-12 months until the end of experiment. Urethane-treated mice received liposomal beta-carotene with drinking water (60 mg/l) 10 days before the beginning of carcinogen treatment and for another 6 months until the end experiment. Water-soluble beta-carotene failed to influence the carcinogenesis in the mammary gland and esophagus in rats; however, it significantly inhibited carcinoma development in murine vagina and cervix uteri (47.0%). Liposomal beta-carotene significantly inhibited lung adenomas (46.4%) and mammary carcinomas (55.6%) in urethane-treated mice.

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Esophageal Neoplasms; Female; Liposomes; Lung Neoplasms; Male; Mammary Neoplasms, Experimental; Mice; Neoplasms, Experimental; Rats; Solubility; Uterine Cervical Neoplasms; Vaginal Neoplasms; Water

Topics: beta Carotene; Cardiovascular Diseases; Dietary Supplements; Environmental Exposure; Humans; Lung Diseases; Lung Neoplasms; Pneumonectomy; Pulmonary Emphysema; Risk Factors; Sleep Apnea Syndromes; Vitamin A

In a hospital-based case control study, we measured serum concentrations of vitamin A, beta-carotene and vitamin E for subjects with cancer (58 cases of lung cancer and 22 cases of stomach cancer) and 63 matched controls in Shenyang, China. Lung cancer patients had significantly (P < 0.01) lower mean serum levels of vitamin A, beta-carotene and vitamin E than controls, while the mean serum level of vitamin E did not differ between stomach cancer patients and the controls. Lower serum levels of vitamin A, vitamin E and beta-carotene were associated with an increased risk of lung cancer. Lower serum levels of vitamin A and beta-carotene were associated with a higher risk of stomach cancer, although the number of cases was small. An increased risk of lung cancer associated with lower serum levels of vitamin A and vitamin E was more evident among heavy smokers than among non-heavy smokers.

Topics: Adult; Aged; Antioxidants; beta Carotene; Case-Control Studies; China; Female; Humans; Lung Neoplasms; Male; Middle Aged; Odds Ratio; Risk Factors; Smoking; Stomach Neoplasms; Vitamin A; Vitamin E

Lung cancers occur more commonly in the upper lobes than in the lower lobes, but its pathophysiologic basis is not well understood. Because numerous studies have reported a consistent inverse relationship between lung cancer risk and intake of certain vegetables and fruits, we hypothesized that the balance between diet-derived protective substances delivered via the circulation and cigarette-derived carcinogenic substances delivered via the airways would be less favorable in the upper lobes compared with the lower lobes, hence accounting for the upper lobe predominance of tumors among smokers. Thus, we examined the association between diet and tumor location in 328 patients with lung cancer. The ratio of upper to lower lobe tumors was 2.5:1.0. In univariate analysis, age, height, weight, sex, race, family history of cancer, education level, tumor histology, calories consumed per day, and intake of animal fat did not differ significantly between patients with upper versus lower lobe tumors. Predictors of tumor location in univariate analysis were family history of lung cancer; smoking history; history of asbestos exposure; and intakes of yellow-orange vegetables, alpha-carotene, beta-carotene, and vitamins A, C, and E. In multivariable logistic regression analysis, the independent predictors of upper lobe tumor location were family history of lung cancer (p = 0.03), history of asbestos exposure (p = 0.02), less intake of yellow-orange vegetables (p < 0.04), and less intake of vitamin E (p = 0.05). Our results show a strong inverse association between upper lobe location of lung cancer and intake of yellow-orange vegetables and vitamin E.

Topics: Administration, Inhalation; Age Factors; Aged; Analysis of Variance; Anticarcinogenic Agents; Antioxidants; Asbestos; Ascorbic Acid; beta Carotene; Carcinogens; Carotenoids; Diet; Dietary Fats; Educational Status; Energy Intake; Female; Forecasting; Fruit; Humans; Logistic Models; Lung; Lung Neoplasms; Male; Racial Groups; Risk Factors; Sex Factors; Smoking; Vegetables; Vitamin A; Vitamin E

Although cigarette smoking is one major determinant of lung carcinogenesis, not all smokers develop cancer. This phenomenon is due to individual variation in genetic susceptibility to carcinogens, nutrition, and lifestyle. Previous studies have shown that genetic polymorphism of metabolic enzymes and plasma micronutrients are associated with lung cancer risk. DNA adducts may serve as a molecular dosimeter for exposure to carcinogens. In this cross-sectional study, we analyzed the blood samples of 158 subjects to evaluate the effects of polymorphisms of cytochrome P450 1A1 (CYP1A1), glutathione S-transferase M1 (GSTM1), T (GSTT), N-acetytransferase 2 (NAT2), and aldehyde dehydrogenase 2 (ALDH2) as well as the effects of plasma beta-carotene and alpha-tocopherol on lymphocyte DNA adducts measured by 32P-postlabeling analysis. The DNA adduct level of smokers (mean +/- SD, 1.26 +/- 0.79/10(8) nucleotides) was significantly higher than that of nonsmokers (0.87 +/- 0.33, P = 0.007). Smokers with CYP1A1 minor homozygotes and GSTM1 null genotypes had a significantly higher level of DNA adducts than those without (P = 0.027 for homozygotes, P = 0.049 for heterozygotes). Smokers with NAT2 minor homozygotes also tended to have a higher DNA adduct level than those with heterozygotes and wild alleles, but the difference was not statistically significant. The DNA adduct level of smokers with ALDH2 heterozygotes was significantly higher than that of smokers with minor homozygotes (P = 0.045). When smokers were divided into "high" and "low" groups according to mean level of plasma beta-carotene or alpha-tocopherol, in the low beta-carotene group, the subjects with CYP1A1 minor homozygotes had higher DNA adduct levels than those with other CYP1A1 genotypes. Smokers with GSTT null genotype and high beta-carotene tended to have a higher DNA adduct level than those with GSTT present and high beta-carotene (P = 0.07), and those with GSTT null genotype and low beta-carotene (P = 0.07). There was weak correlation between DNA adduct level and number of cigarettes smoked per day in the low plasma beta-carotene group (r = 0.28, n = 36, p < 0.1). These results suggested that polymorphisms of CYP1A1, GSTM1, T, NAT2, and ALDH2, and plasma beta-carotene may modulate the level of DNA adducts.

Topics: Adolescent; Adult; beta Carotene; Cell Transformation, Neoplastic; Cross-Sectional Studies; DNA Adducts; Enzymes; Humans; Life Style; Lung Neoplasms; Lymphocytes; Male; Middle Aged; Nutritional Status; Polymorphism, Genetic; Smoking; Vitamin E

Most studies concerning a possible protective role of carotenoids against cancer focus on serum carotenoid levels. We have used Raman microspectroscopy to study the intracellular amounts of carotenoids in lymphocytes of lung cancer patients and of healthy individuals. Our results indicate a significant decrease of carotenoids in lung carcinoma patients compared with healthy individuals, particularly in adenocarcinoma patients. Carotenoid supplementation raised the serum concentration in 2 lung cancer patients up to normal levels, whereas intracellular content remained significantly lower. This indicates that carotenoid uptake by lymphocytes is not only dependent on serum carotenoid concentration. Our findings indicate that Raman microspectroscopy, a recently developed technique to measure intracellular levels of drugs, is also well suited to obtain quantitative data on carotenoid amounts inside cells.

Topics: Adenocarcinoma; Adult; Age Factors; Aged; beta Carotene; Carotenoids; Chromatography, High Pressure Liquid; Cryptoxanthins; Food, Fortified; Humans; Lung Neoplasms; Lycopene; Lymphocytes; Reference Values; Spectrum Analysis, Raman; Xanthophylls

Topics: Anticarcinogenic Agents; beta Carotene; Carcinogens; Clinical Trials as Topic; Drug Synergism; Ethanol; Humans; Isomerism; Lung Neoplasms; Risk; Risk Factors; Smoking; Treatment Outcome; Vitamin A

The authors studied the intake of vegetables, fruits, beta-carotene, and vitamins C and E in relation to the incidence of lung cancer. For 561 men from the town of Zutphen, the Netherlands, dietary history information was obtained in 1960, 1965, and 1970. During 1971-1990, 54 new cases of lung cancer were identified. The data were analyzed using Cox proportional hazard analyses, adjusting for age, pack-years of cigarettes, and energy intake. No relation between intake of vitamin E and lung cancer risk was seen. For vitamin C intake, the results pointed to an inverse association, although not entirely consistently. Furthermore, it was observed that participants with low stable intakes (i.e., low in 1960, 1965, and 1970) of vegetables, fruits, and beta-carotene experienced more than twofold increased relative risks of lung cancer than those with high stable intakes. For participants with low average intakes, relative risks were much lower and not statistically significant. The authors conclude that there is no apparent relation of vitamin E to lung cancer risk; however, for beta-carotene, vitamin C, vegetables, and fruit, most studies, including the present one, suggest weak inverse associations. The use of repeated intake measurements to select subgroups with stable, highly contrasting intakes may be a promising approach for studying diet-cancer relations.

Topics: Ascorbic Acid; beta Carotene; Diet; Diet Surveys; Follow-Up Studies; Fruit; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Netherlands; Proportional Hazards Models; Risk; Vegetables; Vitamin E

Topics: beta Carotene; Food, Fortified; Humans; Incidence; Lung Neoplasms; Risk; Smoking

The results of the ATBC study, the first large intervention trial of antioxidants, were intriguing. While the possibility that beta-carotene may in some circumstances enhance carcinogenesis has now been confirmed in another large trial, the mechanisms of action remain obscure.

Topics: Aged; beta Carotene; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Smoking; Vitamin E

Vegetables and fruits are associated with a reduced risk of cancers, including especially lung cancer. The possible protective compounds include a wide variety of phytochemicals. However, for historical, technical, and biological reasons, a great deal of attention has focused on a single agent: beta-carotene. Recently, in clinical trials, beta-carotene has been shown not to be an effective agent and, perhaps, to be harmful. Possible explanations for this are presented, as is the danger of reductionist approaches to the explanation of the complex nutrition-related biology of cancer.

Topics: Adenomatous Polyps; Apoptosis; beta Carotene; Lung Neoplasms; Mitochondria; Oxidation-Reduction

Topics: beta Carotene; Coronary Disease; Drug Interactions; Ethanol; Finland; Humans; Lung Neoplasms; Myocardial Infarction; Smoking

Lower lobe origin and histologic diagnosis of adenocarcinoma have been described as useful parameters for attributing lung cancer to prior asbestos exposure. To assess whether these characteristics differed between asbestos-exposed individuals and smokers, we evaluated lobe of origin and histologic type of tumors in 78 asbestos-exposed and 214 nonexposed heavy smokers developing lung cancer during the Carotene and Retinol Efficacy Trial (CARET), a prospective cancer chemoprevention trial. Most tumors in both cohorts, regardless of radiographic fibrosis at baseline, originated in upper lobes, representing 67% in asbestos-exposed and 80% in smokers, respectively (adjusted OR for lower lobe = 1.41; 95% CI = 0.69-2.91). Adenocarcinoma represented 32% of lung tumors in the asbestos cohort, and 30% in the smoking cohort (adjusted OR = 0.78; 95% CI = 0.40-1.55), and was inversely associated with radiographic fibrosis (adjusted OR = 0.19; 95% CI = 0.06-0.62). We conclude that neither anatomic site nor histologic cell type of tumors distinguishes effectively between smoking and asbestos as causal factors in development of lung cancer.

Topics: Adenocarcinoma; Anticarcinogenic Agents; beta Carotene; Causality; Confounding Factors, Epidemiologic; Diterpenes; Double-Blind Method; Female; Humans; Lung Neoplasms; Male; Middle Aged; Multicenter Studies as Topic; Occupational Diseases; Occupational Exposure; Prospective Studies; Pulmonary Fibrosis; Randomized Controlled Trials as Topic; Retinyl Esters; Smoking; Vitamin A

Topics: Alcohol Drinking; beta Carotene; Carcinogens; Humans; Lung Neoplasms; Smoking; Vitamin A; Vitamin E

Topics: Animals; Antineoplastic Agents; Antioxidants; beta Carotene; Carotenoids; Clinical Trials as Topic; Female; Humans; Lung Neoplasms; Male; Vitamin A

Topics: Anticarcinogenic Agents; Asbestos; beta Carotene; Carotenoids; Controlled Clinical Trials as Topic; Heart Diseases; Humans; Lung Neoplasms; Neoplasms; Smoking

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; beta Carotene; Carotenoids; Case-Control Studies; Confounding Factors, Epidemiologic; Diet; Fruit; Humans; Lung Neoplasms; Male; Middle Aged; Risk; Smoking; Surveys and Questionnaires; Tracheal Neoplasms; Vegetables

Topics: beta Carotene; Carotenoids; Humans; Lung Neoplasms

Topics: Anticarcinogenic Agents; beta Carotene; Carotenoids; Clinical Trials as Topic; Humans; Lung Neoplasms; Vitamin A

Topics: Anticarcinogenic Agents; beta Carotene; Carotenoids; Controlled Clinical Trials as Topic; Humans; Lung Neoplasms; Smoking

Topics: Aged; Anticarcinogenic Agents; Asbestos; beta Carotene; Cocarcinogenesis; Female; Humans; Lung Neoplasms; Male; Middle Aged; Occupational Diseases; Occupational Exposure; Randomized Controlled Trials as Topic; Risk Factors; Smoking; Vitamin A

Topics: Antioxidants; beta Carotene; Carotenoids; Fruit; Humans; Lung Neoplasms; Vegetables

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; beta Carotene; Cardiovascular Diseases; Contraindications; Humans; Leukoplakia, Oral; Lung Neoplasms; Male; Middle Aged; Randomized Controlled Trials as Topic; Vitamin A; Vitamin E

As part of the multicenter Carotene and Retinol Efficacy Trial (CARET) lung cancer prevention study, we investigated the associations of baseline demographic, health history, and nutritional intake information and the prerandomization serum concentrations of beta-carotene, retinol, retinyl palmitate, and alpha-tocopherol in a random subset of 1182 smokers and asbestos-exposed workers. Dietary intake was estimated via a self-administered food frequency questionnaire using the recently updated United States Department of Agriculture/National Cancer Institute database. In multiple regression analyses, supplemental vitamin use was the strongest predictor of each of the four analytes. There was a statistically significant inverse relationship between smoking and beta-carotene concentrations. Lower serum beta-carotene was associated with current smoking, higher daily cigarettes smoked, and more pack-years. Serum beta-carotene concentrations were higher with increasing years since stopping cigarette use, which suggests a biological mechanism for the lower serum concentration of beta-carotene in smokers. We found weak inverse associations between alcohol intake and the serum concentrations of both beta-carotene and retinol. As in previous reports, dietary intakes as measured by a food frequency questionnaire can only moderately predict serum concentrations of beta-carotene, retinol, retinyl palmitate, and alpha-tocopherol.

Topics: Alcohol Drinking; Anticarcinogenic Agents; Asbestos; beta Carotene; Diet; Diterpenes; Female; Food, Fortified; Humans; Lung Neoplasms; Male; Micronutrients; Middle Aged; Multivariate Analysis; Nutritional Status; Occupational Exposure; Regression Analysis; Retinyl Esters; Smoking; Vitamin A; Vitamin E; Vitamins

Topics: Antioxidants; beta Carotene; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Lung Neoplasms; Smoking; Vitamin A

Increasing evidence suggests that beta-carotene, retinol (vitamin A), and alpha-tocopheral (vitamin E) may have important protective effects in the lung. However, surprisingly little is known about their storage and metabolism in human lung. Levels of beta-carotene, retinol, and alpha-tocopherol in human lung tissues and bronchoalveolar lavage (BAL) cells were determined with reverse-phase high-pressure liquid chromatography (HPLC). Fresh lung tissue, serum, and dietary questionnaires were obtained from 21 patients undergoing open lung surgery, and BAL cells from 12 of these patients. Dietary and serum levels of carotenoids, beta-carotene, retinol, and alpha-tocopherol were consistent with previously reported values. Lung tissue levels of total carotenoids, beta-carotene, retinol, and alpha-tocopherol were respectively 0.34 +/- 0.36 microg/g, 0.13 +/- 0.27 microg/g, 0.15 +/- 0.06 microg/g, and 9.60 +/- 4.86 microg/g tissue. Levels of these nutrients were also measured in BAL cells to establish potential markers for their lung tissue levels. Correlations between serum, BAL-cell, tissue, and dietary levels of the nutrients were determined. Lung tissue levels of total carotenoids, beta-carotene, and alpha-tocopherol, but not retinol, correlated well with their serum levels. Lung tissue levels of retinol and alpha-tocopherol correlated with their BAL-cell levels. These studies demonstrate quantifiable levels of retinol, alpha-tocopherol, and total carotenoids or beta-carotene in human lung tissue and BAL cells, and show that serum and/or BAL-cell levels of these nutrients can potentially be used to predict their lung tissue levels.

Topics: Aged; beta Carotene; Bronchoalveolar Lavage Fluid; Chromatography, High Pressure Liquid; Diet; Female; Humans; Lung; Lung Neoplasms; Macrophages, Alveolar; Male; Middle Aged; Vitamin A; Vitamin E

Topics: Animal Nutritional Physiological Phenomena; Animals; beta Carotene; Clinical Trials as Topic; Disease Models, Animal; Heart Diseases; Humans; Lung Neoplasms; Nutritional Physiological Phenomena; Research Design; Vitamin A

The carotenoid, beta-carotene, has been examined in human trials as a possible lung cancer chemopreventive agent, but initial results indicate that the compound is ineffective. Here we have considered whether beta-carotene could enhance gap junctional intercellular communication (GJIC) and affect the growth of lung epithelial cells, since these effects may be involved in the carotenoid's chemopreventive actions. In accordance with its lack of lung cancer chemopreventive activity, beta-carotene (1-10 microM; 1-5 days treatment durations) did not affect GJIC, gap junction protein (connexin43; Cx43) expression, or growth in vitro of non-transformed (C10) or neoplastic (E9 and 82-132) murine lung epithelial cells. beta-Carotene enhanced GJIC and Cx43 expression and reduced the growth of C3H10T1/2 murine fibroblasts, however. These data indicate that the effects of beta-carotene on GJIC and growth are cell-specific which may partly explain why the carotenoid is an ineffective lung cancer chemopreventive agent.

Topics: Animals; beta Carotene; Cell Communication; Cell Division; Cells, Cultured; Chemoprevention; Connexin 43; Epithelium; Fibroblasts; Gap Junctions; Gene Expression Regulation; Humans; Lung; Lung Neoplasms; Mice; Mice, Inbred C3H; Organ Specificity

Topics: Aged; beta Carotene; Female; Humans; Lung Neoplasms; Male; Middle Aged; Myocardial Infarction; Vitamin A

Topics: Antioxidants; beta Carotene; Humans; Longitudinal Studies; Lung Neoplasms; Male; Randomized Controlled Trials as Topic; Risk Factors; Smoking; Vitamin A

In order to discover the relationship between dietary nutrients intake and risk of lung cancer 1:1 matched case-control study on 156 recent histologiclly diagnosed primary lung cancer patients and 156 patients with respiratory tumour and other related diseases as controls, was conducted in Wuhan. All cases and controls were asked to participate in the nutritional assessment program and a food frequency questionnaire containing 64 food items was filled in. The findings showed that there was a statistically significant difference between dietary intake of beta-carotene between the two groups (2877.13 +/- 393.43 vs. 3445 +/- 430.98 micrograms/day). Having controled the confounding factor of cigarette smoking, a significant linear trend for lower dietary carotene intake toward higher lung cancer risk was observed.

Topics: Adenocarcinoma; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; China; Diet; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nutrition Surveys; Risk Factors; Smoking

Topics: Adult; beta Carotene; Carotenoids; Female; Food, Fortified; Humans; Incidence; Lung Neoplasms; Middle Aged; Smoking; United States; United States Food and Drug Administration; Vitamins

To evaluate if there are differences in lung cancer incidence between socioeconomic groups in the Netherlands and if so, if smoking habits and other lifestyle characteristics could explain these differences.. Prospective cohort study. Baseline measurement included information on socioeconomic status, smoking habits, and other covariates by means of a self-administered questionnaire. Follow up was established by computerised record linkage to cancer registries and a pathology register.. Population originating from 204 municipalities in The Netherlands.. 58,279 men aged 55-69 years in September 1986. After 3.3 years of follow up 490 microscopically confirmed incident lung cancer cases were detected.. An inverse association between lung cancer risk and highest level of education was found, which persisted after adjustment for age, smoking, dietary intake of vitamin C, beta-carotene and retinol (rate ratio (RR) highest/lowest level of education = 0.52, 95% CI 0.33, 0.82, trend p < 0.001). Men with a lower white collar profession had a significantly lower relative rate of lung cancer compared with blue collar workers (RR = 0.66, 95% CI 0.47, 0.96), but after adjustment for smoking habits this difference was reduced (RR = 0.73, 95% CI 0.51, 1.08).. There is an inverse association between highest level of education and lung cancer, which is still apparent after adjustment for age, smoking, dietary intake of vitamin C, beta-carotene and retinol. The significantly lower lung cancer risk of lower white collar workers compared with the risk of blue collar workers could be partially explained by smoking habits.

Topics: Age Factors; Aged; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Cohort Studies; Diet; Educational Status; Follow-Up Studies; Humans; Incidence; Life Style; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Netherlands; Prospective Studies; Risk Factors; Smoking; Social Class; Socioeconomic Factors

It has been hypothesized that beta-carotene mediates the association between low serum cholesterol levels and increased risk of lung cancer. It follows from this assumption that this association should be greater in population strata with a low intake of beta-carotene than in with those with a high intake. To investigate this hypothesis, we analysed dietary beta-carotene, plasma beta-carotene and serum cholesterol levels in 20 male smokers with lung cancer and 103 male smoking controls, a subsample taken from a larger case-control study on oxidant-antioxidant status. As predicted, we found that the association between low serum cholesterol levels and lung cancer risk was greater in subjects with low plasma beta-carotene. Controlling for plasma beta-carotene decreased but did not negate the magnitude of the inverse association between serum cholesterol and lung cancer. A low serum cholesterol level tended to increase the risk associated with low plasma beta-carotene. Our data suggest that a low plasma beta-carotene does not totally explain the association between serum cholesterol and lung cancer.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Carotenoids; Case-Control Studies; Cholesterol; Feeding Behavior; Humans; Lung Neoplasms; Male; Middle Aged; Risk Factors; Smoking

Topics: Antineoplastic Agents; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Cell Transformation, Neoplastic; Humans; Incidence; Lung Neoplasms

The antiproliferative properties of lycopene, the major tomato carotenoid, were compared with those of alpha- and beta-carotene. Lycopene, delivered in cell culture medium from stock solutions in tetrahydrofuran, strongly inhibited proliferation of endometrial (Ishikawa), mammary (MCF-7), and lung (NCI-H226) human cancer cells with half-maximal inhibitory concentration of 1-2 microM; alpha- and beta-carotene were far less effective inhibitors. For example, in Ishikawa cells, a 4-fold higher concentration of alpha-carotene or a 10-fold higher concentration of beta-carotene was needed for the same order of growth suppression. The inhibitory effect of lycopene was detected after 24 hours of incubation, and it was maintained for at least three days. In contrast to cancer cells, human fibroblasts were less sensitive to lycopene, and the cells gradually escaped growth inhibition over time. In addition to its inhibitory effect on basal endometrial cancer cell proliferation, lycopene also suppressed insulin-like growth factor-I-stimulated growth. Insulin-like growth factors are major autocrine/paracrine regulators of mammary and endometrial cancer cell growth. Therefore, lycopene interference in this major autocrine/paracrine system may open new avenues for research on the role of lycopene in the regulation of endometrial cancer and other tumors.

Topics: Anticarcinogenic Agents; beta Carotene; Breast Neoplasms; Carotenoids; Cell Division; DNA; Dose-Response Relationship, Drug; Endometrial Neoplasms; Female; Humans; Insulin-Like Growth Factor I; Lung Neoplasms; Lycopene; Tumor Cells, Cultured

Topics: beta Carotene; Carotenoids; Humans; Lung Neoplasms; Risk Factors; Smoking; Vitamin E

Topics: alpha-Tocopherol; Antioxidants; beta Carotene; Carotenoids; Coloring Agents; Humans; Lung Neoplasms; Quinolines; Tocopherols; Vitamin E

A 1:2 matched case-control study was conducted in Wuhan area with conditional logistic regression model to study the relationship between occurrence of primary lung cancer and serum levels of beta-carotene. The results showed the lower the serum levels of beta-carotene, the higher the risk of lung cancer. It suggested the increase of serum beta-carotene with dietary intake could lower the risk of lung cancer.

Topics: Adjuvants, Immunologic; beta Carotene; Carotenoids; Case-Control Studies; China; Female; Humans; Logistic Models; Lung Neoplasms; Male; Risk Factors

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Carotenoids; Clinical Trials as Topic; Humans; Lung Neoplasms; Neoplasms; Smoking

Topics: beta Carotene; Carotenoids; Clinical Trials as Topic; Humans; Lung Neoplasms; Neoplasms; Oxygen; Photochemistry; Singlet Oxygen; Stomach Neoplasms

Topics: Adult; Aged; Antioxidants; beta Carotene; Carotenoids; Humans; Lung Neoplasms; Selenium; Smoking; Vitamin E

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Carotenoids; Cholesterol; France; Humans; Lung Neoplasms; Male; Middle Aged; Risk Factors

Topics: beta Carotene; Carotenoids; Humans; Incidence; Lung Neoplasms; Vitamin E

Topics: Alcoholism; Animals; beta Carotene; Carotenoids; Drug Synergism; Ethanol; Humans; Lung Neoplasms; Smoking; Vitamin E

Topics: Antioxidants; beta Carotene; Carotenoids; Humans; Lung Neoplasms; Male; Smoking; Vitamin E

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Humans; Lung Neoplasms; Smoking; Vitamin E

Topics: Antioxidants; beta Carotene; Carotenoids; Humans; Lung Neoplasms; Myocardial Ischemia; Risk Factors

Topics: Antioxidants; beta Carotene; Cardiovascular Diseases; Carotenoids; Female; Humans; Lung Neoplasms; Male; Middle Aged; Vitamin E

Topics: beta Carotene; Carotenoids; Finland; Humans; Lung Neoplasms; Male; Randomized Controlled Trials as Topic; Smoking

Topics: beta Carotene; Carotenoids; Humans; Lung Neoplasms; Male; National Institutes of Health (U.S.); Public Policy; Publishing; Risk Factors; Television; United States

Approximately 15% of all lung cancer deaths in the United States (about 22,350 deaths annually) may not be directly attributable to active cigarette smoking. Consumption of beta carotene, which is derived almost exclusively from intake of fruits and vegetables, has been associated with a reduced risk of lung cancer in smokers. However, studies examining this association in nonsmokers, particularly nonsmoking men, are limited.. The purpose of this study was to examine whether dietary factors including beta carotene and retinol are associated with a reduced risk for lung cancer in nonsmoking men and women.. A population-based, matched case-control study of lung cancer in nonsmokers was conducted in New York State from 1982 to 1985. Dietary interviews were completed for 413 individually matched case-control pairs of subjects. To determine whether the relationship between dietary intake from specific food groups and lung cancer differed by type of interview, smoking history, sex, age, or histologic type, we examined data on the case-control pairs from each subgroup separately. The intake of beta carotene and retinol was calculated as the weighted sum of the monthly frequencies of consumption of food items containing these nutrients, where the weights correspond to the nutrient content of a typical portion of the food items.. Consumption of greens (P for trend < .01), fresh fruits (P for trend < .01), and cheese (P for trend < .05) was associated with a significant dose-dependent reduction in risk for lung cancer, whereas consumption of whole milk (P for trend < .01) was associated with a significant dose-dependent increase in risk. Use of vitamin E supplements was also protective (odds ratio = 0.55; 95% confidence interval [CI] = 0.35-0.85). Increased consumption of the following food groups was associated with a reduction in risk among females: vegetables (P for trend < .025), raw fruits and vegetables (P for trend < .005), and dairy products (P for trend < .025). In males, increased consumption of raw fruits and vegetables was associated with a reduced risk for lung cancer (P for trend < .005). Dietary beta carotene (OR = 0.70; 95% CI = 0.50-0.99), but not retinol (OR = 0.98; 95% CI = 0.82-1.17), was significantly associated with risk reduction.. This is the largest study to date of dietary factors and lung cancer in nonsmokers; results suggest that dietary beta carotene, raw fruits and vegetables, and vitamin E supplements reduce the risk of lung cancer in nonsmoking men and women.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Carotenoids; Case-Control Studies; Diet; Dose-Response Relationship, Drug; Female; Fruit; Humans; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; New York; Smoking; Vegetables; Vitamin A; Vitamin E

Topics: Adjuvants, Immunologic; Adult; AIDS-Related Complex; Animals; Antimutagenic Agents; beta Carotene; Bleomycin; Breast Diseases; Carotenoids; Chemotherapy, Adjuvant; Chromosome Aberrations; Diet; Female; Humans; Lung Neoplasms; Lymphocytes; Male; Menstruation Disturbances; Mice; Mice, Inbred BALB C; Pain; Rats

Topics: Anticarcinogenic Agents; beta Carotene; Carcinoma, Small Cell; Carotenoids; Cell Division; Cell Line; Gene Expression; Genes, myc; Humans; Kinetics; Lung Neoplasms; RNA, Messenger; Tumor Cells, Cultured

Beta-carotene at concentration of 6.25 micrograms/ml was shown to inhibit significantly the colony forming efficiency (CFE) of cultured human lung cancer 801 cell line and at 12.5 micrograms/ml was shown to completely inhibit CFE. A 42%-68% (P < 0.01) decrease in spontaneous lung metastasis of LA795 murine pulmonary adenocarcinoma was observed when T739 inbred strain mice were fed a diet with beta-carotene (25mg/100g diet). Ability of DNA and RNA synthesis of lung cancer cells were decreased (P < 0.05) after treating with beta-carotene (25 micrograms/ml) by 24 hours, but the ability for DNA synthesis of human lymphocytes was not effected by the same treatment. Expression of ras oncogene was proved to be inhibited by beta-carotene because the product of ras p21 proteins of cancer cells was decreased after treating by beta-carotene.

Topics: Adenocarcinoma; Animals; beta Carotene; Carotenoids; DNA, Neoplasm; Genes, ras; Humans; Lung Neoplasms; Mice; Oncogene Protein p21(ras); RNA, Neoplasm; Tumor Cells, Cultured; Tumor Stem Cell Assay

Selenium has been suggested to be anticarcinogenic and to play a role in the cellular defense against oxidative stress. The association between toenail selenium (a marker of long-term selenium status) and lung cancer was investigated in a cohort study of diet and cancer that started in 1986 among 120,852 Dutch men and women aged 55-69 years. After 3.3 years of follow-up, 550 incident cases of lung carcinoma were detected. Toenail selenium data were available for 370 lung cancer cases and 2459 members of a randomly selected subcohort. The rate ratio of lung cancer for subjects in the highest compared to the lowest quintile of toenail selenium, after controlling for age, gender, smoking, and education, was 0.50 (95% confidence interval, 0.30-0.81), with a significant inverse trend across quintiles (P = 0.006). The protective effect of selenium was concentrated in subjects with a relatively low dietary intake of beta-carotene or vitamin C. The rate ratio in the highest compared to the lowest quintile of selenium was 0.45 in the low beta-carotene group (95% confidence interval, 0.22-0.92; trend P = 0.028) and 0.36 in the low vitamin C group (95% confidence interval, 0.17-0.75; trend P < 0.001). The results of this study support an inverse association between selenium status and lung cancer and suggest a modification of the effect of selenium by the antioxidants beta-carotene and vitamin C.

Topics: Adenocarcinoma; Age Factors; Aged; Ascorbic Acid; beta Carotene; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Carotenoids; Cohort Studies; Education; Feeding Behavior; Female; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Nails; Netherlands; Prospective Studies; Risk Factors; Selenium; Sex Factors; Smoking; Surveys and Questionnaires; Time Factors; Toes; Vitamin A

Topics: beta Carotene; Carotenoids; Digestive System Neoplasms; Humans; Lung Neoplasms

The hypotheses that the antioxidant vitamin E provides protection against lung cancer and that this hypothetical protection is modified by smoking status were investigated using two different study designs--a cohort study and a nested case-control study--among Finnish men aged 15 years and over. In the cohort study the association between vitamin E intake and lung cancer risk was studied among 5,254 individuals with 121 lung cancer cases that occurred during a 19-year follow-up, and in the nested case-control study the association between serum vitamin E level and lung cancer risk was studied using 144 lung cancer cases and 270 matched controls as a basis. There was a significant inverse association between vitamin E status and lung cancer occurrence among nonsmokers but not among smokers in both designs. The relative risk of lung cancer between the lowest and highest tertiles of vitamin E intake was 3.3 among nonsmokers and 0.8 among smokers. The corresponding results for serum vitamin E were 6.6 and 0.8, respectively. Nonsmokers with simultaneously low serum levels of vitamin E and other micronutrients (i.e., beta-carotene, retinol and selenium) had a 12-fold greater risk of lung cancer in comparison with men having more satisfactory levels. The corresponding number among smokers was three. The results suggest that vitamin E status is primarily associated with lung cancer risk among nonsmokers. Firm conclusions can, however, be drawn only on the basis of intervention trials.

Topics: Adolescent; Adult; Aged; beta Carotene; Carotenoids; Case-Control Studies; Cohort Studies; Diet; Dose-Response Relationship, Drug; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Nutrition Surveys; Risk Factors; Selenium; Smoking; Vitamin A; Vitamin E

Although beta-carotene has been considered to be a key cancer preventive agent in green and yellow vegetables, other types of carotenoids, such as alpha-carotene, may also contribute to anticarcinogenic action, since these carotenoids usually coexist with beta-carotene and are detectable in human blood and tissues. In this study, we compared the inhibitory effect of natural alpha-carotene, obtained from palm oil, with that of beta-carotene on spontaneous liver carcinogenesis in C3H/He male mice. The mean number of hepatomas per mouse was significantly decreased by alpha-carotene supplementation (per os administration in drinking water at a concentration of 0.05%, ad libitum) as compared with that in the control group (P < 0.001, Student's t test). On the other hand, beta-carotene, at the same dose as alpha-carotene, did not show any such significant difference from the control group. Furthermore, we also compared the antitumor-promoting activity of alpha-carotene with that of beta-carotene against two-stage mouse lung carcinogenesis (initiator, 4-nitroquinoline 1-oxide; promoter, glycerol). alpha-Carotene, but not beta-carotene, reduced the number of lung tumors per mouse to about 30% of that in the control group (P < 0.001, Student's t test). The higher potency of the antitumor-promoting action of alpha-carotene compared to beta-carotene was confirmed in other experimental systems; e.g., alpha-carotene was also found to have a stronger effect than beta-carotene in suppressing the promoting activity of 12-O-tetradecanoylphorbol-13-acetate on skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated mice. These results suggest that not only beta-carotene, but also other types of carotenoids, such as alpha-carotene, may play an important role in cancer prevention.

Topics: 4-Nitroquinoline-1-oxide; 9,10-Dimethyl-1,2-benzanthracene; Administration, Oral; Animals; beta Carotene; Carotenoids; Drug Screening Assays, Antitumor; Humans; Liver Neoplasms; Lung Neoplasms; Male; Mice; Mice, Inbred C3H; Ornithine Decarboxylase; Papilloma; Skin Neoplasms; Specific Pathogen-Free Organisms; Tetradecanoylphorbol Acetate

In the first part of this study we have shown how the serum levels of four selected tumour markers, namely tissue polypeptide antigen (TPA), carcino-embryonic antigen (CEA), hyaluronic acid (HA) and ferritin, display patterns characteristic of mesothelioma (M) or bronchogenic carcinoma (BC) in asbestos-exposed workers, and we hypothesize that the differences in marker patterns correspond to differences in carcinogenesis mechanisms. In a preliminary study, we found these specific marker patterns in 5/19 exposed workers of whom only one demonstrated any radiological signs of disease. Thus these specific marker patterns may be early events, occurring long (possibly years) before the classical radiological signs of exposure to asbestos. Accordingly they afford an optimal opportunity for prevention which should be adapted to the carcinogenesis mechanism as it is revealed by the marker pattern; it is aimed at antagonizing free radical carcinogenesis in all persons with TPA levels in excess of 100 U/l or Ferritin in excess of 400 ng/ml, and at inhibiting chemical carcinogenesis in those having elevated CEA levels (over 3 ng/ml). The mechanisms involved in these inhibitory processes are described and discussed, as well as the practical implementations that proceed from them. A prevention trial is now being started among 300 active and retired workers of an asbestos-cement works in northern France; the design of the study is presented. This prevention programme should be maintained over many years and holds a strong potential for reducing the untoward effects of exposure to asbestos.

Topics: Acetylcysteine; Antigens, Neoplasm; Asbestos; Ascorbic Acid; beta Carotene; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Bronchogenic; Carotenoids; Cohort Studies; Ferritins; Humans; Hyaluronic Acid; Longitudinal Studies; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Occupational Diseases; Occupational Exposure; Peptides; Riboflavin; Selenium; Tissue Polypeptide Antigen; Vitamin A; Vitamin E

Increased intake of vegetables, fruits, and carotenoids and elevated blood levels of beta-carotene are consistently associated with reduced risk of lung cancer in epidemiologic studies. Epidemiologic research also suggests that carotenoids may reduce the risk of other cancers, although the evidence is less extensive and consistent. The simplest explanation is that beta-carotene is protective. However, the possible roles of other carotenoids, other constituents of vegetables and fruits, and associated dietary patterns have not been adequately explored. To evaluate these alternative hypotheses, we are undertaking three lines of research. (a) With dietary data from the 1987 National Health Interview Survey and the 1982-1984 Epidemiologic Follow-up of the first National Health and Nutrition Examination Study, we have determined which food groups and nutrients are highly correlated with vegetable and fruit intake. (b) We have developed and characterized a liquid chromatography method for optimal recovery and resolution of the common carotenoids in blood, specifically lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and beta-carotene. (c) In a population-based case-control study of lung cancer in white men in New Jersey, we are assessing whether estimates of the intake of the individual carotenoids might produce stronger inverse associations than estimates of provitamin A carotenoids based on current food composition tables.

Topics: beta Carotene; Carotenoids; Case-Control Studies; Chromatography, Liquid; Diet Surveys; Energy Intake; Fruit; Humans; Lung Neoplasms; Neoplasms; Prospective Studies; Retrospective Studies; Stomach Neoplasms; Vegetables

This study compares the toxic effects of the carotenoids, beta-carotene and canthaxanthin, and alpha-tocopherol (vitamin E) on human tumor cells and their normal counterparts in vitro. Seven different malignant cell lines were examined: oral carcinoma (two cell lines), breast (two cell lines), lung carcinoma (two cell lines), and malignant melanoma. The in vitro cell culture assays showed a consistent morphologic change in the affected tumor cells following treatment with carotenoid or vitamin E. A rounding of the tumor cells and eventual lifting off the tissue culture plate were observed. These changes were apparent after 1 to 5 hours of treatment depending on the tumor cell line. Associated with these observable cellular changes were quantitative reductions in proliferation (3H-thymidine proliferation) and succinic dehydrogenase activity (MTT assay). In addition, there was a noticeable change in protein expression, with an increased expression of a 70-kD protein following treatment with beta-carotene. This protein was associated with tumor cells showing a decrease in proliferation (oral carcinoma, malignant melanoma) but not with normal keratinocytes or melanocytes. These studies substantiate a selective cytotoxic effect on human tumor cell growth by carotenoids and alpha-tocopherol in vitro, and may provide an explanation of the therapeutic activity of these agents and their possible use in the treatment of premalignancy or early oral carcinoma.

Topics: beta Carotene; Breast Neoplasms; Canthaxanthin; Carcinoma, Squamous Cell; Carotenoids; Cell Division; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Humans; Keratinocytes; Lung Neoplasms; Melanocytes; Melanoma; Mouth Neoplasms; Neoplasm Proteins; Succinate Dehydrogenase; Tumor Cells, Cultured; Vitamin E

A cohort of 5,080 men living in a retirement community in California (United States) and initially free from lung cancer were followed from June 1981 to December 1989. At recruitment, each study participant completed a mailed questionnaire which requested information on the subject's medical history, use of cigarettes, and usual consumption frequencies during the preceding 12 months of 44 vegetable and fruit items. Men who had never smoked had the highest mean daily intake of beta-carotene (8,505 micrograms), followed by past smokers (7,761 micrograms) and then by current smokers (6,178 micrograms). beta-Carotene intake of the subject's wife was correlated significantly with that of the husband in the 4,018 spouse pairs (r = 0.46; P = 0.0001). Among men with similar smoking habits, dietary beta-carotene intake significantly decreased with the spouse's smoking habit: never, past, and current smokers (P = 0.004; test for linear trend). During 31,477 person-years of follow-up, 125 incident cases of lung cancer were observed among the cohort of 5,080 men. Age-adjusted relative risks for lung cancer were below unity (i.e., demonstrating a reduced risk) for higher relative to lower consumption of beta-carotene, of all vegetables and fruits, and of yellow vegetables alone. However, these relative risks approached or crossed the null value when adjusted for personal smoking.

Topics: Aged; beta Carotene; California; Carotenoids; Diet; Follow-Up Studies; Housing for the Elderly; Humans; Lung Neoplasms; Marriage; Prospective Studies; Risk Factors; Smoking; Surveys and Questionnaires; Tobacco Smoke Pollution

In a case-control study to determine the risk of developing lung cancer, the serum levels of vitamins A and E, carotene and selenium were determined in 31 patients, newly diagnosed as having lung cancer, and in matched controls, the said controls being selected from outpatients with no cancer. A significant, inverse association was found between serum vitamins A and E and lung cancer. The relative risk for the low vs high tertiles were, respectively, 5.94 for serum vitamin A and 8.44 for serum vitamin E. Taking histological cancer subtype into account, no relation was revealed between the microelements and squamous cell carcinoma of the lung. The relative risk for lung cancer was 6.50, however, when three, or all four, microelement levels were in the lowest tertile, compared with there being fewer than three in the lowest tertile. Even when three microelements, excluding vitamin E which had the most significant inverse association with lung cancer, were considered, the relative risk was 7.50 when any two or all three were in the lowest tertile, compared with there being just one microelement or none at all in the lowest tertile. A combined effect of vitamins A and E, carotene and selenium on the development of lung cancer has, therefore, been suggested. Further studies will thus be necessary to elucidate the cumulative effect of the serum micronutrients and trace elements, as well as the effect of single elements, on the development of lung cancer.

Topics: Adenocarcinoma; Adult; Aged; beta Carotene; Carcinoma; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Risk Factors; Selenium; Smoking; Vitamin A; Vitamin E

This paper hypothesizes that beta-carotene mediates the association between low serum cholesterol and increased risk of lung cancer, predicts that the association should be greater in population strata with low intake of beta-carotene than in those with high intake if the hypothesis is correct, and investigates this prediction with data from a 24-year cohort study of 1,960 middle-aged employed men. In the total cohort, serum cholesterol was not related to risk of lung cancer. The relative risk associated with a difference of -1.0 mmol per liter in serum cholesterol was 1.01 (95% confidence interval of 0.80-1.27) after adjustment for cigarette smoking, age, and intake of beta-carotene. In contrast, however, when the study group was restricted to men with intake of beta-carotene less than 5,000 (N = 929) or less than 3,000 IU per day (N = 272), comparable relative risks were 1.10 and 1.21, respectively. Although the 95% confidence intervals for these relative risks were broad and included unity, the result is consistent with expectation. We conclude that the hypothesis warrants further investigation.

Topics: Adult; beta Carotene; Carotenoids; Chicago; Cholesterol; Cohort Studies; Diet; Humans; Lung Neoplasms; Male; Middle Aged; Risk Factors; Smoking

Topics: beta Carotene; Carotenoids; Humans; Lung Neoplasms

The hypothesis that dietary cholesterol is positively associated with lung cancer was investigated in a 24-year cohort study of 1,878 middle-aged men who were employed in 1958 by the Western Electric Company in Chicago. The relative risk of lung cancer associated with an increment in dietary cholesterol of 500 mg/day was 1.9 (95 percent confidence interval 1.1-3.4) after adjustment for cigarettes, age, and intake of beta-carotene and fat. Results suggested that the association was specific to cholesterol from eggs. Further research is needed to understand the basis for this association.

Topics: Adenocarcinoma; Adult; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Chicago; Cholesterol, Dietary; Cohort Studies; Dietary Fats; Eggs; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Risk; Smoking

In 1971-1973 at the third examination of the Basel Study started in 1959, the major antioxidant vitamins and carotene were measured in the plasma of 2974 men. A subsample and their families were reinvestigated in 1977-79. During the 12-y observation period (1973-85) 553 men died, 204 of cancer (lung cancer 68, stomach cancer 20; colon cancer 17, all other malignancies 99). We found significantly lower mean carotene levels for all cancer, bronchus cancer, and stomach cancer (all P less than 0.01) compared with the 2421 survivors. The relative risk of subjects with low carotene (less than 0.23 mumol/L) was significantly elevated (P less than 0.05) for lung cancer (Cox's model). Higher risks were noted for all cancer (P less than 0.01) if both carotene and retinol were low. Low plasma carotene which is known to reflect carotene intake is in our study associated with increased cancer risk.

Topics: Adult; Age Factors; Ascorbic Acid; beta Carotene; Carotenoids; Cholesterol; Cohort Studies; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prospective Studies; Risk Factors; Sex Factors; Smoking; Stomach Neoplasms; Switzerland; Triglycerides; Vitamin A; Vitamin E

Dietary carotene intake during the year before diagnosis was estimated for 96 men with lung cancer, 75 men with other epithelial cancers, and 97 hospital controls. Relative to those of men in the lowest third of carotene intake (less than 1,683 micrograms/day), the smoking-adjusted odds ratios for men in the middle (1,683-2,698 micrograms/day) and upper (greater than 2,698 micrograms/day) thirds of carotene intake were 0.67 and 0.45, respectively, for lung cancer (one-sided test for trend, p = 0.048) and 0.63 and 0.65, respectively, for other epithelial cancers (one-sided test for trend p = 0.074). The protective effect of estimated dietary carotene intake was considerably stronger than was the effect of total intake of carotene-rich vegetables and fruits (grams per day), providing some evidence that the protective factor is carotene itself rather than another component of vegetables and fruits.

Topics: Aged; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; Diet; Humans; Lung Neoplasms; Male; Middle Aged; Odds Ratio; Risk Factors; Smoking; Surveys and Questionnaires; Vitamin A; Vitamin E; Zinc

A unique case-control study design including family members of cases and controls was used to assess the association between serum beta-carotene and cancer. The cases (n = 389) were incident cancer cases diagnosed between 1981 and 1984 in Wellington, New Zealand, and the controls (n = 391) were hospital patients without cancer. Both cases and controls were on a home diet at the time beta-carotene levels were measured. Since findings concerning patients who have already been diagnosed with cancer may reflect changes that occurred subsequent to development of cancer, family members of cancer patients (n = 618) and control patients (n = 675) were included, giving a total of 2,073 study participants. Low levels of beta-carotene were observed for individuals with a number of cancers, including cancers of the lung stomach, esophagus, small intestine, cervix, and uterus. Low levels of beta-carotene were also found in the relatives of these cancer patients. These differences persisted after stratification by current cigarette smoking. The strongest findings were those for lung cancer. Excluding adenocarcinoma, lung cancer patients had average serum beta-carotene levels of 40.2 micrograms/dl, 25.9 micrograms/dl lower than those of controls, adjusted for age, sex, and length of sample storage (p less than 0.01). Family members of the lung cancer patients also had lower values than family members of control patients, with an adjusted difference of 10.8 micrograms/dl (p less than 0.01). Odds ratio estimates for lung cancer by quartiles of beta-carotene residuals ranged from 3.6 (90% confidence interval (CI) 1.1-12.2) for the second-highest quartile to 6.6 (90% CI 1.9-23.0) for the lowest quartile (test for trend, p less than 0.001). Patients with cancers of the breast, colon, prostate, and skin did not have lower levels of serum beta-carotene than expected. Family members of individuals with these cancers also did not have lower levels of serum beta-carotene. The cancer sites that were associated with serum beta-carotene are, in general, sites for which smoking is a strong risk factor, and the sites that were not associated with beta-carotene do not have smoking as a risk factor.

Topics: Adenocarcinoma; Adult; beta Carotene; Carotenoids; Case-Control Studies; Family; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; New Zealand; Smoking

Topics: beta Carotene; Carotenoids; Female; Humans; Lung Neoplasms; Male; Tobacco Smoke Pollution

Several factors are known to promote the development of a lung cancer. Smoking, occupation, environment, chronic bronchitis, and scars in the lung are all risk factors. Many studies have stressed the importance of nutrition, in particular vitamins. Vitamin A is necessary for cell differentiation. Retrospective and prospective studies have proven the inverse relation between provitamin A, beta-carotene, and lung cancer of the squamous and oat cell types. Studies in which beta-carotene or natural vitamin A are supplied to smokers, controls, and patients after resection for lung cancer are in progress. The study of other vitamins such as vitamin C and vitamin E has not led to definitive conclusions. The trace element selenium may also exert a beneficial effect.

Topics: beta Carotene; Carotenoids; Humans; Lung Neoplasms; Nutritional Requirements; Retrospective Studies; Risk Factors; Vitamin A; Vitamin A Deficiency

Topics: beta Carotene; Carotenoids; Cholesterol, Dietary; Dietary Fats; Hawaii; Humans; Lung Neoplasms

We conducted a population-based study of diet and lung cancer among the multiethnic population of Hawaii in 1983-1985. We completed interviews for 230 men and 102 women with lung cancer and 597 men and 268 women controls, frequency-matched to the patients by age and sex. A quantitative dietary history assessed the usual intake of foods rich in vitamins A and C and carotenoids. A clear dose-dependent negative association was demonstrated between dietary beta-carotene and lung cancer risk in both sexes. After adjusting for smoking and other covariates, the men in the lowest quartile of beta-carotene intake had an odds ratio of 1.9 (95% confidence interval, 1.1-3.2) compared to those in the highest quartile of intake. The corresponding odds ratio for women was 2.7 (95% confidence interval, 1.2-6.1). No clear association was found for retinol, vitamin C, folic acid, iron, dietary fiber, or fruits. All vegetables, dark green vegetables, cruciferous vegetables, and tomatoes showed stronger inverse associations with risk than beta-carotene. This observation suggests that other constituents of vegetables, such as lutein, lycopene, and indoles, and others, may also protect against lung cancer in humans.

Topics: Ascorbic Acid; beta Carotene; Carotenoids; Dietary Fiber; Epidemiologic Methods; Female; Folic Acid; Hawaii; Humans; Lung Neoplasms; Male; Risk; Smoking; Vegetables; Vitamin A

Topics: Adult; Age Factors; Aged; Aged, 80 and over; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; China; Dose-Response Relationship, Drug; Feeding Behavior; Humans; Lung Neoplasms; Male; Middle Aged; Risk Factors; Smoking; Vitamin A

Topics: Asbestos; beta Carotene; Carotenoids; Diet; Humans; Lung Neoplasms; Occupational Diseases; Preventive Medicine; Retinoids; Vitamin A

Plasma and dietary levels of retinol and beta-carotene were evaluated in a consecutive series of 47 females with histologically proven primary lung cancer and 159 nonneoplastic hospital controls. The dietary questionnaire included 69 different items: special care was given to foods rich in vitamin A and seasonal foods (e.g., vegetables and fruits), whereas serum analysis was focused on retinol and beta-carotene. Age-adjusted mean values for cases and controls were, respectively, 458.3 vs. 551.3 mg for plasma retinol, 276.1 vs. 390.1 mg for plasma carotene; 598.1 vs 820.6 mg for daily retinol, and 628.0 vs. 882.5 mg for dietary carotene. The odds ratios for low vs. high tertile, adjusted for age, smoking, retinol or carotene, cholesterol, and triglycerides by multivariate analysis were, respectively, 1.13 for plasma retinol, 5.04 for plasma carotene, 3.27 for dietary retinol, and 2.93 for dietary carotene. For all the examined items, there was a trend of increased risk for the second and third tertile, and statistical significance was reached for plasma beta-carotene (p less than 0.05). The hypothesis that a higher risk of lung cancer is related to a low vitamin A consumption is supported by these data.

Topics: Aged; beta Carotene; Carotenoids; Diet; Epidemiologic Methods; Female; Humans; Lung Neoplasms; Middle Aged; Smoking; Vitamin A

Many investigations suggested relations between fat soluble vitamin levels in blood and incidence of cancer. These studies are concerning both therapeutical efficiency of vitamins intake, seric levels and cancer risk, and the supposed correlation between blood fat soluble vitamin levels and the cancer localization. The purpose of the present study was to investigate whether the alterations of fat soluble vitamin levels (A-vitamin, beta-carotene and alpha-tocopherol) were correlated not only to carcinogenic processes but also to the localizations of their developments. In a former article, we have found that an abnormal ketone derivative of D3 vitamin (1-keto-24-methyl-25-hydroxycholecalciferol) or carcinomedin was present in the serum of all cancer patients and absent in that of healthy control subjects. Serum levels of the four above substances were determined in 1068 subjects suffering from differently localized cancers and in 880 healthy subjects. A statistical multidimensional analysis of data led a separate five groups of cancer types (p less than 0.001). Within each group alterations of vitamin spectra, compared to controls, were identical; between groups they were significantly different. These groups were: anal and intestinal cancer; pancreatic, hepatic, oesophageal and gastric cancer; laryngeal and lung cancer; uro-genital and breast cancer; brain cancer. All these groups are statistically different from the reference one (p less than 0.001). This grouping roughly corresponds to the embryologic origin of affected organs. This suggests that carcinogenesis may alter fat soluble vitamin metabolism, specifically in various forms of cancer, or these alterations of vitamin metabolism are in some way involved in the carcinogenic process.

Topics: Adult; beta Carotene; Breast Neoplasms; Calcitriol; Carotenoids; Digestive System Neoplasms; Female; Humans; Intestinal Neoplasms; Laryngeal Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasms; Nervous System Neoplasms; Urogenital Neoplasms; Vitamin A; Vitamin E

Topics: Aged; Ascorbic Acid; beta Carotene; Carotenoids; Colonic Neoplasms; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prospective Studies; Rectal Neoplasms; Smoking; Stomach Neoplasms; Switzerland; Vitamin A; Vitamin E

A cohort of 10,473 residents of Leisure World, Laguna Hills, CA, who were initially free of cancer were followed from 1981 to 1986. A health survey questionnaire completed by all cohort members included usual frequencies of consumption of certain food items, including vegetables, fruits, dairy products, liver, and cereal, as well as specific information on brand and formulation of vitamin supplements containing vitamins A, C, or E. Pathologic diagnosis of incident cancer was confirmed in 643 persons (56 lung, 110 colon, 59 bladder, 93 prostate, 123 female breast, and 202 cancers of other sites). Our study found little indication that increased intake of vitamin A or beta-carotene from the diet or supplements protects against the development of cancer overall. Dietary vitamin A intake was highly associated with smoking status; 25% of current smokers were in the highest third of dietary vitamin A consumption versus 32% of past smokers and 36% of never-smokers. In males who never smoked there was some indication that cancer rates decreased with increasing vitamin A intake, but the results were not statistically significant.

Topics: beta Carotene; Carotenoids; Diet; Female; Humans; Lung Neoplasms; Male; Neoplasms; Prospective Studies; Risk; Smoking; Vitamin A

Topics: Adult; Ascorbic Acid; beta Carotene; Carotenoids; Humans; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Selenium; Uric Acid; Vitamin A; Vitamins

We studied the relation of serum vitamin A (retinol), beta-carotene, vitamin E, and selenium to the risk of lung cancer, using serum that had been collected during a large blood-collection study performed in Washington County, Maryland, in 1974. Levels of the nutrients in serum samples from 99 persons who were subsequently found to have lung cancer (in 1975 to 1983) were compared with levels in 196 controls who were matched for age, sex, race, month of blood donation, and smoking history. A strong inverse association between serum beta-carotene and the risk of squamous-cell carcinoma of the lung was observed (relative odds, 4.30; 95 percent confidence limits, 1.38 and 13.41). Mean (+/- SD) levels of vitamin E were lower among the cases than the controls (10.5 +/- 3.2 vs. 11.9 +/- 4.90 mg per liter), when all histologic types of cancer were considered together. In addition, a linear trend in risk was found (P = 0.04), so that persons with serum levels of vitamin E in the lowest quintile had a 2.5 times higher risk of lung cancer than persons with levels in the highest quintile. These data support an association between low levels of serum vitamin E and the risk of any type of lung cancer and between low levels of serum beta-carotene and the risk of squamous-cell carcinoma of the lung.

Topics: Aged; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Humans; Lung Neoplasms; Male; Maryland; Middle Aged; Risk; Selenium; Smoking; Vitamin A; Vitamin E

Topics: Ascorbic Acid; beta Carotene; Blood Pressure; Body Composition; Carotenoids; Colonic Neoplasms; Diet; Female; Humans; Life Style; Lipids; Lung Neoplasms; Male; Neoplasms; Prospective Studies; Risk; Smoking; Stomach Neoplasms; Vitamin B Complex; Vitamin E; Vitamins

A case-control study among white women in Los Angeles County was conducted to investigate the role of smoking and other factors in the etiology of lung cancer in women. A total of 149 patients with adenocarcinoma (ADC) and 71 patients with squamous cell carcinoma (SCC) of the lung and their age- and sex-matched controls were interviewed. Personal cigarette smoking accounted for almost all of SCC and about half of ADC in this study population. Among nonsmokers, slightly elevated relative risk(s) (RR) for ADC were observed for passive smoke exposure from spouse(s) [RR = 1.2; 95% confidence interval (Cl) = 0.5, 3.3] and at work (RR = 1.3; 95% Cl = 0.5, 3.3). Childhood pneumonia (RR = 2.7; 95% Cl = 1.1, 6.7) and childhood exposure to coal burning (RR = 2.3; 95% Cl = 1.0, 5.5) were additional risk factors for ADC. For both ADC and SCC, increased risks were associated with decreased intake of beta-carotene foods but not for total preformed vitamin A foods and vitamin supplements.

Topics: Adenocarcinoma; beta Carotene; California; Carotenoids; Dairy Products; Diet; Epidemiologic Methods; Female; Humans; Lung Diseases; Lung Neoplasms; Occupations; Population Surveillance; Risk; Smoking; Tobacco Smoke Pollution; Vitamin A

Serum specimens were obtained from over 6800 men of Japanese ancestry in Hawaii from 1971 to 1975. Since then, the following numbers of newly diagnosed cancer cases have been identified: 81 colon, 74 lung, 70 stomach, 32 rectum, and 27 urinary bladder. The stored sera of the cases and 302 controls were tested to determine their beta-carotene, vitamin A, and vitamin E levels. There was no association of either vitamin A or E with any of the cancers. For serum beta-carotene, there was a significant association only with lung cancer (20.0 micrograms/dl in cases versus 29.0 in controls, P less than 0.005). The lung cancer odds ratio for men in the lowest quintile of beta-carotene was 3.4 relative to men in the highest quintile. These findings suggest that a low serum beta-carotene level is a predictor of increased lung cancer risk in men.

Topics: beta Carotene; Carotenoids; Hawaii; Humans; Japan; Lung Neoplasms; Male; Middle Aged; Neoplasms; Risk; Vitamin A; Vitamin E; Vitamins

In addition to frequency of consumption, a food frequency questionnaire may assess amount consumed, often by using food models, and the stability of diet. A food frequency interview directed at preformed vitamin A and beta-carotene was administered to 130 cases and 309 controls in an ongoing population-based case-control study of lung cancer in New Mexico. The questionnaire measured frequency, amount, and stability of consumption for 55 food items. Different combinations of responses to these three types of questions were used to calculate indices of total vitamin A consumption. The index based on frequency alone had the lowest value and increased significantly when amount was combined with frequency. Consideration of past consumption had relatively little effect on absolute and relative estimates of intake. Spearman rank order correlations between index pairs were high. These results suggest that the use of frequency alone is appropriate when the objective of data collection is to establish subjects' relative intake of specific nutrients.

Topics: Adult; Aged; beta Carotene; Carotenoids; Data Collection; Diet Surveys; Female; Food; Humans; Interviews as Topic; Lung Neoplasms; Male; Middle Aged; New Mexico; Nutrition Surveys; Regression Analysis; Surveys and Questionnaires; Vitamin A