beta-carotene and Colorectal-Neoplasms

Antioxidants, such as vitamin A, C and E, selenium and β-carotene, have been proposed as possible agents in the chemoprevention of colorectal cancer and have been the subject of recent trials and reviews. This review aimed to assess the present evidence on the effect of antioxidants on the incidence of colorectal neoplasms in the general population.. A systematic review of randomized controlled trials was undertaken comparing antioxidants alone or in combination with other agents vs placebo. The following databases were searched for published and unpublished literature: Cochrane Library, MEDLINE, PreMEDLINE, CINAHL, EMBASE, Web of Science, and Biological Abstracts and Research Registers. Studies were quality appraised and extracted. Meta-analysis was performed.. Twelve studies were identified as relevant. In the nine comparing antioxidants with no antioxidants (n=148 922), there was no difference in the incidence of colorectal cancer [relative risk (RR) 1.00, 95% confidence interval (CI) 0.88-1.13]. One study assessed the effect of antioxidants on adenoma formation (n=15 538) and did not demonstrate a statistically significant effect (RR 1.47, 95% CI 0.97-2.23). Of 14 discrete analyses for different combinations of antioxidants, only one reported a statistically significant increase in relative risk of adenoma formation in participants receiving vitamin E (RR 1.74, 95% CI 1.09-1.79, P=0.02) or vitamin E plus β-carotene (RR 1.63, 95% CI 1.01-2.63, P=0.04). Effectiveness did not seem to differ between healthy populations, participants with cardiovascular risk factors or populations exposed to smoking or asbestos.. The review demonstrates that antioxidants (vitamin A, C and E, selenium and β-carotene), as single agents, in combination with other antioxidants or in combination with other agents, are not effective in the chemoprevention of colorectal neoplasia in the general population. This questions their involvement in future randomized controlled trials of chemoprevention in colorectal cancer.

Topics: Adenoma; Antioxidants; Ascorbic Acid; beta Carotene; Colorectal Neoplasms; Humans; Selenium; Vitamin A; Vitamin E

Colorectal cancer (CRC) is the third most common cancer in the UK: incidence increases with age, median age at diagnosis being over 70 years. Approximately 25% of cases occur in individuals with a family history of CRC, including 5% caused by familial adenomatous polyposis (FAP) or hereditary non-polyposis CRC (HNPCC). Most develop from adenomatous polyps arising from the intestine lining. Individuals with these polyps undergo polypectomy and are invited for endoscopic surveillance. Screening via faecal occult blood testing has been rolled out across the UK.. To evaluate the clinical effectiveness and cost-effectiveness of drug and micronutrient interventions for the prevention of CRC and/or adenomatous polyps. Interventions considered include: non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and cyclo-oxygenase-2 (COX-2) inhibitors; folic acid; calcium; vitamin D and antioxidants (including vitamin A, vitamin C, vitamin E, selenium and beta-carotene). Chemoprevention was assessed in the general population, in individuals at increased risk of CRC, and in individuals with FAP or HNPCC.. A systematic review identified randomised controlled trials (RCTs) assessing drug and nutritional agents for the prevention of CRC or adenomatous polyps. A separate search identified qualitative studies relating to individuals' views, attitudes and beliefs about chemoprevention. MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, CINAHL, the Cochrane Database of Systematic Reviews, Cochrane CENTRAL Register of Controlled Trials, DARE, NHS-EED (NHS Economic Evaluation Database), HTA database, Science Citation Index, BIOSIS previews and the Current Controlled Trials research register were searched in June 2008. Data were extracted by one reviewer and checked by a second.. The synthesis methods used were systematic review and meta-analysis for RCTs and qualitative framework synthesis for qualitative studies. A health economic model was developed to assess the cost-effectiveness of chemoprevention for two populations with different levels of risk of developing CRC: the general population and an intermediate-risk population.. The search identified 44 relevant RCTs and six ongoing studies. A small study of aspirin in FAP patients produced no statistically significant reduction in polyp number but a possible reduction in polyp size. There was a statistically significant 21% reduction in risk of adenoma recurrence [relative risk (RR) 0.79, 95% confidence interval (CI) 0.68 to 0.92] in an analysis of aspirin versus no aspirin in individuals with a history of adenomas or CRC. In the general population, a significant 26% reduction in CRC incidence was demonstrated in studies with a 23-year follow-up (RR 0.74, 95% CI 0.57 to 0.97). Non-aspirin NSAID use in FAP individuals produced a non-statistically significant reduction in adenoma incidence after 4 years of treatment and follow-up and reductions in polyp number and size. In individuals with a history of adenomas there was a statistically significant 34% reduction in adenoma recurrence risk (RR 0.66, 95% CI 0.60 to 0.72) and a statistically significant 55% reduction in advanced adenoma incidence (RR 0.45, 95% CI 0.35 to 0.58). No studies assessed the effect of non-aspirin NSAIDs in the general population. There were no studies of folic acid in individuals with FAP or HNPCC. There was no significant effect of folic acid versus placebo on adenoma recurrence (RR 1.16, 95% CI 0.97 to 1.39) or advanced adenoma incidence in individuals with a history of adenomas. In the general population there was no significant effect of folic acid on risk of CRC (RR 1.13, 95% CI 0.77 to 1.64), although studies were of relatively short duration. Calcium use by FAP patients produced no significant reduction in polyp number or disease progression. In individuals with a history of adenomas there was a statistically significant 18% reduction in risk of adenoma recurrence (RR 0.82, 95% CI 0.69 to 0.98) and a non-significant reduction in risk of advanced adenomas (RR 0.77, 95% CI 0.50 to 1.17). In the general population there was no significant effect of calcium on risk of CRC (RR 1.08, 95% CI 0.87 to 1.34), although studies were of relatively short duration. There were no studies of antioxidant use in individuals with FAP or HNPCC, and in individuals with a history of adenomas no statistically significant differences in relative risk of adenoma recurrence were found. In the general population there was no difference in incidence of CRC (RR 1.00, 95% CI 0.88 to 1.13) with antioxidant use compared with no antioxidant use. Twenty studies reported qualitative fi. Whilst a number of studies were included in the review, the duration of follow-up was generally insufficient to detect an effect on cancer incidence. Given the uncertainties and ambiguities in the evidence base, the results of the health economic analysis should be interpreted with caution.. Aspirin and celecoxib may reduce recurrence of adenomas and incidence of advanced adenomas in individuals with an increased risk of CRC and calcium may reduce recurrence of adenomas in this group. COX-2 inhibitors may decrease polyp number in patients with FAP. There is some evidence for aspirin reducing the incidence of CRC in the general population. Both aspirin and NSAIDs are associated with adverse effects so it will be important to consider the risk-benefit ratio before recommending these agents for chemoprevention. The economic analysis suggests that chemoprevention has the potential to represent a cost-effective intervention, particularly when targeted at intermediate-risk populations following polypectomy.

Topics: Adenomatous Polyposis Coli; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; beta Carotene; Calcium; Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; Cyclooxygenase 2 Inhibitors; Folic Acid; Humans; Incidence; Models, Economic; Prognosis; Risk Assessment; Selenium; United Kingdom

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

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

Colorectal cancer is the third most incident cancer in the United States and is second only to lung cancer as a cause of cancer-related mortality. Colorectal cancer develops through a multistep process characterized by histopathological precursor lesions and molecular genetic alterations. This sequential process of tumorigenesis provides opportunities for the development and testing of both primary and secondary prevention strategies. This review focuses on chemoprevention, which is defined as the use of natural or synthetic agents to reverse the process of carcinogenesis. Epidemiological studies have consistently shown that chronic intake of nonsteroidal anti-inflammatory drugs (NSAIDs), principally aspirin, can reduce the incidence of colorectal adenomas and carcinomas. Evaluation of NSAIDs, including newer selective cyclo-oxygenase-2 inhibitors, in carcinogen-induced and genetically manipulated animal models of colorectal cancer demonstrates that these drugs are effective chemopreventive agents. In humans, the NSAID sulindac has been studied in familial adenomatous polyposis patients and was found to regress colorectal adenomas in a placebo-controlled trial. More recently, the selective cyclo-oxygenase-2 inhibitor Celebrex was also shown to be effective in familial adenomatous polyposis and was approved by the Food and Drug Administration as a adjuct to usual care in these patients. NSAIDs, as well as other chemopreventive agents, are currently being studied in patients at increased risk of colorectal cancer, including those with sporadic adenomas. The outcome of these studies has the potential to impact patient management practices. However, chemopreventive agents cannot be recommeded at present for average-risk individuals or for those with sporadic colorectal neoplasia. In addition to demonstrating efficacy, chemopreventive agents must be safe and well tolerated for chronic administration and should be relatively cost-effective. Although still in its infancy, the field of chemoprevention is an exciting and rapidly advancing area of investigation. Chemopreventive strategies, if effective, offer the promise of producing a paradigm shift in our current approach to colorectal cancer.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; beta Carotene; Calcium Compounds; Colorectal Neoplasms; Dietary Fiber; Dietary Supplements; Eflornithine; Enzyme Inhibitors; Female; Folic Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Male; Prognosis; Risk Assessment; Sensitivity and Specificity; Ursodeoxycholic Acid; Vitamin E

Aspirin and other NSAIDs are showing promise in the chemoprevention of colorectal cancer. Ongoing trials will eventually provide still lacking information about the optimum dose and treatment duration. NSAIDs may also help to lower the risk of cancer in other organs such as the oesophagus, and possibly breast, stomach, and lung. The chemoprevention by NSAIDs should be seen not as the sole method of prevention, but as an additional tool which will be accompanied by other approaches such as stopping smoking, limiting alcohol consumption, and eating more fruits and vegetables. The chemoprevention by NSAIDs needs also to be balanced against the risks of toxicity (particularly in the stomach) and the other beneficial effects such as prevention of cardiovascular morbidity and mortality. Some of the NSAID induced gastric ulceration and bleeding will most likely be avoided by adopting the use of cyclooxygenase-2 (COX-2) selective NSAIDs, which will selectively inhibit COX-2 while sparing COX-1.

Topics: Adult; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; beta Carotene; Case-Control Studies; Child; Cohort Studies; Colorectal Neoplasms; Cricetinae; Cyclooxygenase Inhibitors; Esophageal Neoplasms; Humans; Neoplasms; Pancreatic Neoplasms; Prospective Studies; Prostaglandin Antagonists; Prostaglandins; Randomized Controlled Trials as Topic; Skin Neoplasms; Stomach Neoplasms; Time Factors

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

Some 15 years ago there began to emerge a consensus among epidemiologists that diet might be responsible for 30-60% of cancers in the developed world, in the sense that it should be possible to reduce age-specific incidence rates by this amount by practicable dietary change. Within about 6 years it was also broadly agreed that the principal changes required to bring about this effect were a reduction in the consumption of fat; an increase in the consumption of fruit, green and yellow vegetables, dietary fiber, and some micronutrients; and possibly an improvement in the methods of food preservation. Very small effects, if any, were attributed to food additives and to the pollution of food by trace pesticides, which the public, who accepted much of the consensus advice, have increasingly regarded as important causes of risk. These past conclusions are reviewed in the light of increased knowledge of the etiology of cancer and the trends in its incidence. Contrary to common belief, the trends are broadly encouraging.

Topics: Age Factors; beta Carotene; Breast Neoplasms; Carotenoids; Colorectal Neoplasms; Dietary Fats; Dietary Fiber; Feeding Behavior; Humans; Incidence; Male; Neoplasms; Prostatic Neoplasms; Sex Factors

We previously reported a positive association between serum 25-hydroxyvitamin D (25(OH)D) and colorectal cancer risk. To further elucidate this association, we examined the molar ratio of 25(OH)D to vitamin D binding protein (DBP), the primary 25(OH)D transport protein, and whether DBP modified the association between 25(OH)D and colorectal cancer risk.. In a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, controls were 1∶1 matched to 416 colorectal cancer cases based on age and date of blood collection. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for quartiles of 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, a proxy for free, unbound circulating 25(OH)D.. Comparing highest to lowest quartiles, DBP was not associated with colorectal cancer risk (OR = 0.91; 95% CI: 0.58, 1.42, p for trend  = 0.58); however, a positive risk association was observed for the molar ratio of 25(OH)D:DBP (OR = 1.44; 95% CI: 0.92, 2.26, p for trend  = 0.04). In stratified analyses, the positive association between 25(OH)D and colorectal cancer was stronger among men with DBP levels above the median (OR = 1.89; 95% CI: 1.07, 3.36, p for trend  = 0.01) than below the median (OR = 1.20; 95% CI: 0.68, 2.12, p for trend  = 0.87), although the interaction was not statistically significant (p for interaction  = 0.24).. Circulating DBP may influence the association between 25(OH)D and colorectal cancer in male smokers, with the suggestion of a stronger positive association in men with higher DBP concentrations. This finding should be examined in other populations, especially those that include women and non-smokers.

Topics: alpha-Tocopherol; beta Carotene; Case-Control Studies; Colorectal Neoplasms; Double-Blind Method; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Risk; Risk Factors; Vitamin D; Vitamin D-Binding Protein

Previous epidemiologic observational and experimental studies investigated the potential of antioxidant micronutrients to modulate cancer risk, but these studies produced inconsistent results. In this pilot, randomized, double-blind, placebo-controlled clinical trial (n = 47), we assessed the effects of an antioxidant micronutrient combination (800 mg dl-alpha-tocopherol acetate, 24 mg beta-carotene, 1.0 g vitamin C, 200 microg l-selenomethionine, 7.2 mg riboflavin, 80 mg niacin, 60 mg zinc, 5 mg manganese) given daily over 4 months on oxidative and inflammatory biomarkers in patients with a history of sporadic colorectal adenoma. Plasma tumor necrosis factor-alpha (TNF-alpha), interleukin-6, and F2-isoprostane concentrations were measured using ELISAs, and cystine (CySS) was measured using high-performance liquid chromatography. Plasma TNF-alpha concentration decreased in the active treatment group by 37% relative to the placebo group (P = 0.002), and CySS decreased by 19% (P = 0.03); however, interleukin-6 and F2-isoprostane concentrations decreased in antioxidant-treated nonsmokers but increased in smokers, although these findings were not statistically significant. The decreases of TNF-alpha and CySS were more pronounced in nonsmokers. These data suggest that (a) an antioxidant micronutrient cocktail can modulate biomarkers of oxidative stress and inflammation in humans and (b) the effects of antioxidant micronutrient supplementation on biomarkers of inflammation and oxidative stress may differ according to smoking status.

Topics: Adenoma; Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers, Tumor; Chromatography, High Pressure Liquid; Colorectal Neoplasms; Cystine; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; F2-Isoprostanes; Female; Humans; Interleukin-6; Male; Manganese; Micronutrients; Middle Aged; Niacin; Oxidative Stress; Pilot Projects; Riboflavin; Selenomethionine; Tumor Necrosis Factor-alpha; Vitamin E; Zinc

In two large, randomized prevention trials, supplementation with beta-carotene increased the risk of lung cancer. Subjects in these studies were predominantly cigarette smokers, and the adverse effects were concentrated among those who also drank alcohol. Although beta-carotene supplementation appeared not to increase the risk of cancer generally, it is not clear if smoking and/or alcohol use alters the effect of beta-carotene on carcinogenesis at sites outside the lung.. We studied the effect of beta-carotene supplementation on colorectal adenoma recurrence among subjects in a multicenter double-blind, placebo-controlled clinical trial of antioxidants for the prevention of colorectal adenomas. A total of 864 subjects who had had an adenoma removed and were polyp-free were randomly assigned (in a factorial design) to receive beta-carotene (25 mg or placebo) and/or vitamins C and E in combination (1000 mg and 400 mg, respectively, or placebo), and were followed with colonoscopy for adenoma recurrence 1 year and 4 years after the qualifying endoscopy. A total of 707 subjects had two follow-up examinations and provided smoking and alcohol use data. Adjusted multivariate risk ratios (RRs) and 95% confidence intervals (CIs) were used to assess the effects of beta-carotene on adenoma recurrence.. Among subjects who neither smoked cigarettes nor drank alcohol, beta-carotene was associated with a marked decrease in the risk of one or more recurrent adenomas (RR = 0.56, 95% CI = 0.35 to 0.89), but beta-carotene supplementation conferred a modest increase in the risk of recurrence among those who smoked (RR = 1.36, 95% CI = 0.70 to 2.62) or drank (RR = 1.13, 95% CI = 0.89 to 1.43). For participants who smoked cigarettes and also drank more than one alcoholic drink per day, beta-carotene doubled the risk of adenoma recurrence (RR = 2.07, 95% CI = 1.39 to 3.08; P for difference from nonsmoker/nondrinker RR <.001).. Alcohol intake and cigarette smoking appear to modify the effect of beta-carotene supplementation on the risk of colorectal adenoma recurrence.

Topics: Adenoma; Adult; Aged; Alcohol Drinking; Anticarcinogenic Agents; Antioxidants; beta Carotene; Colorectal Neoplasms; Double-Blind Method; Female; Humans; Male; Middle Aged; Smoking; Treatment Outcome

To study the association between dietary and serum antioxidant vitamins and carotenoids and risk for colorectal cancer in male smokers.. A prospective cohort study within a randomised, double-blind, placebo-controlled trial testing supplementation with alpha-tocopherol (50 mg/day), beta-carotene (20 mg/day) or both in preventing cancer.. Participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study with complete dietary data and serum samples available from baseline. These included 26,951 middle-aged male smokers among whom 184 colorectal cancer cases were diagnosed during 8 y of follow-up. Relative risks were calculated with Cox proportional hazards models adjusting for trial supplementation, age, body mass index, serum cholesterol, cigarettes smoked per day and physical activity.. There was no significant association between dietary vitamin C or E, alpha-or gamma-tocopherol, retinol, alpha- or beta-carotene, lycopene or lutein+zeaxanthin and risk for colorectal cancer. Serum alpha-tocopherol, beta-carotene or retinol was also not associated with the risk, neither did the season when baseline blood was drawn modify the relationship between serum beta-carotene and colorectal cancer risk.. Our data support the results from previous studies in which no association between dietary antioxidant vitamins and carotenoids and risk for colorectal cancer has been observed. Likewise, no association between baseline serum antioxidant concentrations and colorectal cancer risk was evident.. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study was supported by a contract with the US National Cancer Institute (N01-CN-45165).

Topics: Aged; alpha-Tocopherol; Anticarcinogenic Agents; Antioxidants; beta Carotene; Cohort Studies; Colorectal Neoplasms; Dietary Supplements; Double-Blind Method; Humans; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors; Smoking; Vitamin A

Some epidemiological investigations suggest that higher intake or biochemical status of vitamin E and beta-carotene might be associated with reduced risk of colorectal cancer.. We tested the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of colorectal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, placebo-controlled trial among 29,133 50-69-year-old male cigarette smokers. Participants were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or a placebo daily for 5-8 years. Incident colorectal cancers (n = 135) were identified through the nationwide cancer registry, and 99% were histologically confirmed. Intervention effects were evaluated using survival analysis and proportional hazards models.. Colorectal cancer incidence was somewhat lower in the alpha-tocopherol arm compared to the no alpha-tocopherol arm, but this finding was not statistically significant (relative risk (RR) = 0.78, 95% confidence interval (CI) 0.55-1.09; log-rank test p = 0.15). Beta-carotene had no effect on colorectal cancer incidence (RR = 1.05, 95% CI 0.75-1.47; log-rank test p = 0.78). There was no interaction between the two substances.. Our study found no evidence of a beneficial or harmful effect for beta-carotene in colorectal cancer in older male smokers, but does provide suggestive evidence that vitamin E supplementation may have had a modest preventive effect. The latter finding is in accord with previous research linking higher vitamin E status to reduced colorectal cancer risk.

Topics: Aged; beta Carotene; Colorectal Neoplasms; Dietary Supplements; Double-Blind Method; Finland; Humans; Incidence; Male; Middle Aged; Risk Factors; Smoking; Vitamin E

Epidemiological and experimental studies have indicated that dietary factors such as vitamin C, vitamin E, and beta-carotene are associated with the risk of colorectal cancer. This study was carried out within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study), whose participants were randomly assigned to four supplementation groups: (a) alpha-tocopherol (AT), 50 mg/day; (b) beta-carotene (BC), 20 mg/day; (c) both AT and BC; and (d) placebo. We included the 15,538 ATBC Study participants who had been randomized within the areas of three major cities in southern Finland. Cases of colorectal adenoma (n = 146) were identified by the pathology laboratories in the study areas, and these participants' medical records were collected and reviewed. Alpha-tocopherol supplementation increased the risk for adenomas (relative risk, 1.66; 95% confidence interval, 1.19-2.32), whereas beta-carotene supplementation had no effect on the risk (relative risk, 0.98; 95% confidence interval, 0.71-1.35). Slightly more prediagnosis rectal bleeding and intestinal pain occurred in those adenoma cases who received alpha-tocopherol supplements than in those who did not. Thus, some bias may have resulted, with alpha-tocopherol supplementation leading to more colonoscopies and, thus, to an increased detection of incident polyps in this group. This is further supported by the trial finding that alpha-tocopherol supplementation did not increase the risk of colorectal cancer.

Topics: Adenoma; Aged; Antioxidants; beta Carotene; Bias; Colorectal Neoplasms; Double-Blind Method; Drug Therapy, Combination; Finland; Humans; Incidence; Male; Middle Aged; Proportional Hazards Models; Risk Factors; Smoking; Vitamin E

Folate derivatives are important in experimental colorectal carcinogenesis; low folate intake, particularly with substantial alcohol intake, is associated with increased risk. The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate, required for purine and thymidine syntheses, to 5-methyltetrahydrofolate, the primary circulatory form of folate necessary for methionine synthesis. A common mutation (677C-->T) in MTHFR reduces enzyme activity, leading to lower levels of 5-methyltetrahydrofolate. To evaluate the role of folate metabolism in human carcinogenesis, we examined the associations of MTHFR mutation, plasma folate levels, and their interaction with risk of colon cancer. We also examined the interaction between genotype and alcohol intake. We used a nested case-control design within the Physicians' Health Study. Participants were ages 40-84 at baseline when alcohol intake was ascertained and blood samples were drawn. During 12 years of follow-up, we identified 202 colorectal cancer cases and matched them to 326 cancer-free controls by age and smoking status. We genotyped for the MTHFR polymorphism and measured plasma folate levels. Men with the homozygous mutation (15% in controls) had half the risk of colorectal cancer [odds ratio (OR), 0.49; 95% confidence interval (CI), 0.27-0.87] compared with the homozygous normal or heterozygous genotypes. Overall, we observed a marginal significant increased risk of colorectal cancer (OR, 1.78; 95% CI, 0.93-3.42) among those whose plasma folate levels indicated deficiency (<3 ng/ml) compared with men with adequate folate levels. Among men with adequate folate levels, we observed a 3-fold decrease in risk (OR, 0.32; 95% CI, 0.15-0.68) among men with the homozygous mutation compared with those with the homozygous normal or heterozygous genotypes. However, the protection due to the mutation was absent in men with folate deficiency. In men with the homozygous normal genotype who drank little or no alcohol as reference, those with the homozygous mutation who drank little or no alcohol had an 8-fold decrease in risk (OR, 0.12; 95% CI, 0.03-0.57), and for moderate drinkers, a 2-fold decrease in risk (OR, 0.42; 95% CI, 0.15-1.20); no decrease in risk was seen in those drinking 1 or more drinks/day. Our findings provide support for an important role of folate metabolism in colon carcinogenesis. In particular, these results suggest that the 677C-->IT mutation

Topics: Adult; Aged; Aged, 80 and over; Alcohol Drinking; Aspirin; beta Carotene; Case-Control Studies; Cocarcinogenesis; Colorectal Neoplasms; Diet; DNA Methylation; DNA Replication; Double-Blind Method; Folic Acid; Folic Acid Deficiency; Genetic Predisposition to Disease; Genotype; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Odds Ratio; Oxidoreductases Acting on CH-NH Group Donors; Point Mutation; Polymorphism, Genetic; Prospective Studies; Risk; Tetrahydrofolates; United States

Topics: Adenoma; Antineoplastic Agents; beta Carotene; Carotenoids; Colorectal Neoplasms; Dietary Fats; Dietary Fiber; Humans; Randomized Controlled Trials as Topic

We investigated the association between self-reported alcohol ingestion and colorectal cancer in a cohort of male smokers in Finland. Among 27,109 men aged 50 to 69 years, 87 colon and 53 rectal cases were diagnosed during the five to eight years of follow-up. Among drinkers, colorectal cancer risk increased with the amount of alcohol consumed (P trend = 0.01) with risk increasing by 17 percent for each drink consumed. Both beer and spirits contributed to this increased risk. Further analyses revealed that the positive association with alcohol was primarily for colon cancer (P trend = 0.01). Interestingly, risk of colorectal cancer associated with drinking (cf self-reported abstinence) changed with follow-up time, suggesting an inverse association for alcohol early in follow-up, and a positive association after about three-and-a-half years of follow-up. Follow-up time did not modify the positive association with amount of alcohol among drinkers, however. Results also indicated that beta-carotene supplementation may attenuate the effect of alcohol on colorectal cancer risk among drinkers. In conclusion, this study supports a role for alcohol in colon carcinogenesis and suggests that similar studies should evaluate carefully the effects of lifetime drinking habits and recent abstinence.

Topics: Aged; Alcohol Drinking; Antineoplastic Agents; beta Carotene; Carotenoids; Cohort Studies; Colorectal Neoplasms; Finland; Follow-Up Studies; Humans; Male; Middle Aged; Risk Factors; Smoking; Time Factors

Epidemiologic evidence of associations between the high intake of fat and low intake of dietary fiber, beta carotene, and other dietary constituents and the risk of colorectal neoplasia has been inconsistent and has not provided a sufficient basis for recommendations concerning the dietary prevention of large-bowel cancer in humans.. We conducted a clinical trial to assess the effects on the incidence of adenomas of reducing dietary fat to 25% of total calories and supplementing the diet with 25 g of wheat bran daily and a capsule of beta carotene (20 mg daily).. We performed a randomized, partially double-blinded, placebo-controlled factorial trial in which half the patients were assigned to each intervention, resulting in seven intervention groups and one control group. Eligibility criteria included histologic confirmation of at least one colorectal adenoma and confidence expressed by the colonoscopist that all polyps had been removed. Dietary changes were individually initiated and monitored by dietitians and research nurses. At surveillance colonoscopy, the size and location of all polyps were recorded, and their histology was later centrally reviewed. Among 424 patients who were randomly assigned in the trial, 13 were found to be ineligible upon histologic review. Among the remaining 411, complete outcome data were collected from 390 at 24 months and from 306 at 48 months. All P values are from two-sided tests of statistical significance.. There was no statistically significant prevention of total new adenomas with any of the interventions. We found a statistically non-significant reduced risk of large adenomas (> or = 10 mm) with the low-fat intervention: At 24 months, the odds ratio (OR) adjusted for potential confounders = 0.4 and 95% confidence interval (CI) = 0.1-1.1; at 48 months, OR = 0.3 and 95% CI = 0.1-1.0. Less and statistically nonsignificant reductions in the risk of large adenomas were found with wheat bran: At 24 months, OR = 0.8 and 95% CI = 0.3-2.2; at 48 months, OR = 0.8 and 95% CI = 0.3-2.5. Patients on the combined intervention of low fat and added wheat bran had zero large adenomas at both 24 and 48 months, a statistically significant finding (P = .03).. Because only small numbers of patients were studied, our finding that the combination of fat reduction and a supplement of wheat bran reduced the incidence of large adenomas in this randomized, controlled trial must be treated with caution. The results do suggest, however, that these interventions may reduce the transition from smaller to larger adenomas, a step that may critically define those adenomas most likely to progress to malignancy.

Topics: Adenoma; Adult; Aged; Anticarcinogenic Agents; beta Carotene; Carotenoids; Colorectal Neoplasms; Dietary Fats; Dietary Fiber; Double-Blind Method; Female; Humans; Male; Middle Aged

The effect of beta-carotene supplementation on major serum carotenoid fractions (lutein/zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and beta-carotene) was investigated in 224 people with colorectal adenomas (139 men, 85 women) recruited for the Australian Polyp Prevention Project (APPP). Each subject was randomly assigned to take either 20 mg beta-carotene/d or placebo over 24 mo. Besides the expected increase in serum concentration of beta-carotene (1073% in men, 839% in women), lycopene (176% in men) and alpha-carotene (211% in men and 166% in women) concentrations were also increased after body mass index, baseline concentration, change in respective carotenoid intake, and other confounding factors were adjusted for. The increase in serum concentrations of these carotenoids after beta-carotene supplementation suggests that beta-carotene may interact biologically with other carotenoids and such interaction would need to be taken into consideration when the protective effect of beta-carotene supplementation for cancer or other diseases is examined.

Topics: Adenoma; Adult; Aged; beta Carotene; Body Mass Index; Carotenoids; Colorectal Neoplasms; Cryptoxanthins; Dietary Fats; Double-Blind Method; Energy Intake; Female; Humans; Lipids; Lutein; Lycopene; Male; Middle Aged; Placebos; Xanthophylls; Zeaxanthins

People who consume a diet high in vegetables and fruits have a lower risk of cancer of the large bowel. Antioxidant vitamins, which are present in vegetables and fruits, have been associated with a diminished risk of cancers at various anatomical sites. We conducted a randomized, controlled clinical trial to test the efficacy of beta carotene and vitamins C and E in preventing colorectal adenoma, a precursor of invasive cancer.. We randomly assigned 864 patients, using a two-by-two factorial design, to four treatment groups, which received placebo; beta carotene (25 mg daily); vitamin C (1 g daily) and vitamin E (400 mg daily); or the beta carotene plus vitamins C and E. In order to identify new adenomas, we performed complete colonoscopic examinations in the patients one year and four years after they entered the study. The primary end points for analyses were new adenomas identified after the first of these two follow-up examinations.. Patients adhered well to the prescribed regimen, and 751 completed the four-year clinical trial. There was no evidence that either beta carotene or vitamins C and E reduced the incidence of adenomas; the relative risk for beta carotene was 1.01 (95 percent confidence interval, 0.85 to 1.20); for vitamins C and E, it was 1.08 (95 percent confidence interval, 0.91 to 1.29). Neither treatment appeared to be effective in any subgroup of patients or in the prevention of any subtype of polyp defined by size or location.. The lack of efficacy of these vitamins argues against the use of supplemental beta carotene and vitamins C and E to prevent colorectal cancer. Although our data do not prove definitively that these antioxidants have no anticancer effect, other dietary factors may make more important contributions to the reduction in the risk of cancer associated with a diet high in vegetables and fruits.

Topics: Adenomatous Polyps; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Colonic Polyps; Colorectal Neoplasms; Confidence Intervals; Female; Follow-Up Studies; Humans; Male; Middle Aged; Risk; Vitamin E; Vitamins

Higher dietary quality is associated with lower disease risks and has not been examined extensively with lipidomic profiles.. Our goal was to examine associations of the Healthy Eating Index (HEI)-2015, Alternate HEI-2010 (AHEI-2010), and alternate Mediterranean Diet Index (aMED) diet quality indices with serum lipidomic profiles.. We conducted a cross-sectional analysis of HEI-2015, AHEI-2010, and aMED with lipidomic profiles from 2 nested case-control studies within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (n = 627) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 711). We used multivariable linear regression to determine associations of the indices, derived from baseline food-frequency questionnaires (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial: 1993-2001, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: 1985-1988) with serum concentrations of 904 lipid species and 252 fatty acids (FAs) across 15 lipid classes and 28 total FAs, within each cohort and meta-analyzed results using fixed-effect models for lipids significant at Bonferroni-corrected threshold in common in both cohorts.. Adherence to HEI-2015, AHEI-2010, or aMED was associated positively with 31, 41, and 54 lipid species and 8, 6, and 10 class-specific FAs and inversely with 2, 8, and 34 lipid species and 1, 3, and 5 class-specific FAs, respectively. Twenty-five lipid species and 5 class-specific FAs were common to all indices, predominantly triacylglycerols, FA22:6 [docosahexaenoic acid (DHA)]-containing species, and DHA. All indices were positively associated with total FA22:6. AHEI-2010 and aMED were inversely associated with total FA18:1 (oleic acid) and total FA17:0 (margaric acid), respectively. The identified lipids were most associated with components of seafood and plant proteins and unsaturated:saturated fat ratio in HEI-2015; eicosapentaenoic acid plus DHA in AHEI-2010; and fish and monounsaturated:saturated fat ratio in aMED.. Adherence to HEI-2015, AHEI-2010, and aMED is associated with serum lipidomic profiles, mostly triacylglycerols or FA22:6-containing species, which are related to seafood and plant proteins, eicosapentaenoic acid-DHA, fish, or fat ratio index components.

Topics: alpha-Tocopherol; Animals; beta Carotene; Colorectal Neoplasms; Cross-Sectional Studies; Diet; Diet, Mediterranean; Eicosapentaenoic Acid; Female; Finland; Humans; Lipidomics; Male; Ovarian Neoplasms; Smokers; Triglycerides; United States

Fucoxanthin is a marine xanthophyll found in edible brown algae, and a metabolite, fucoxanthinol (FxOH), possesses a potent apoptosis inducing effect in many cancer cells. Chloride intracellular channel 4 (CLIC4) is a member of the CLIC family that plays an important role in cancer development and apoptosis. However, the role of CLIC4 in FxOH-induced apoptosis is not well understood. In this study, we investigated whether CLIC4 affects the apoptotic properties of FxOH in human colorectal cancer (CRC) cells under FxOH treatment. Treating human CRC DLD-1 cells with 5.0 μmol/L FxOH significantly induced apoptosis. FxOH downregulated CLIC4, integrin β1, NHERF2 and pSmad2 (Ser

Topics: Apoptosis; beta Carotene; Cell Proliferation; Chloride Channels; Colorectal Neoplasms; Humans

Fucoxanthinol (FxOH) is a strong anticancer metabolite of fucoxanthin that accumulates in abundance in edible brown algae and promises human health benefits. FxOH has been shown to suppress tumorigenicity and sphere formation in human colorectal cancer stem cell (CCSC)-like spheroids (colonospheres, Csps). In the present study, we aimed to clarify the inhibitory activity of FxOH on epithelial-mesenchymal transition (EMT), which is essential for cancer recurrence and distant metastasis, and to identify intracellular low-molecular-weight metabolites that may be useful for evaluating the cellular effects of FxOH on CCSCs. FxOH significantly suppressed sphere-forming activity, migration and invasion in a dose-dependent manner. In addition, treatment with 50 µmol/l FxOH suppressed N-cadherin and vimentin expression and the activation of integrin signaling linked to EMT suppression by western blot analysis. MAPK signaling and STAT signaling related to cell growth and apoptosis in Csps derived from human CRC HT-29 and HCT116 cells were also altered. According to our metabolite profiling by GC-MS analysis, reduced glycine and succinic acid levels were correlated with EMT suppression and apoptosis induction in Csps. Our data indicate that simple amino acids such as glycine and succinic acid may be good prognostic indicators of physiological changes to CCSCs induced by FxOH treatment.

Topics: Apoptosis; beta Carotene; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Glycine; HCT116 Cells; HT29 Cells; Humans; Mitogen-Activated Protein Kinase Kinases; Neoplastic Stem Cells; Spheroids, Cellular; STAT Transcription Factors; Succinic Acid

Previous epidemiological studies on the association between circulating carotenoids and the risk of colorectal cancer drew inconclusive conclusions. This study aimed to examine serum carotenoids in relation to colorectal cancer risk in a Chinese population.. One case-control study beginning from July 2010, consecutively recruited 538 eligible colorectal cancer cases and 564 age (5-year interval) and sex frequency-matched controls. Serum levels of α-carotene, β-carotene, β-cryptoxanthin, lycopene and lutein/zeaxanthin were detected by HPLC. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence internal (CI) after adjusting for various confounders. Serum levels of α-carotene, β-cryptoxanthin and lycopene were found to be inversely associated with colorectal cancer risk. The adjusted ORs of the highest quartile relative to the lowest quartile serum level were 0.49 (95% CIs 0.33-0.72) for α-carotene, 0.44 (95% CIs 0.29-0.66) for β-cryptoxanthin, and 0.36 (95% CIs 0.24-0.54) for lycopene, respectively. The association between serum β-carotene, lutein/zeaxanthin and colorectal cancer risk was not statistically significant.. The results indicated that the incidence of colorectal cancer was associated with lower serum levels of α-carotene, β-cryptoxanthin and lycopene among Chinese population residing in Guangdong.

Topics: Adult; Aged; beta Carotene; Beta-Cryptoxanthin; Body Mass Index; Carotenoids; Case-Control Studies; China; Colorectal Neoplasms; Cryptoxanthins; Female; Humans; Incidence; Logistic Models; Lycopene; Male; Middle Aged; Risk Factors; Socioeconomic Factors

Fucoxanthin (Fx), one of the major xanthophylls in brown algae, is known to be effective for colorectal cancer (CRC) chemoprevention through inhibiting cell growth, cell cycle and caspase activation. Recently, we observed fucoxanthinol (FuOH), an anti-cancer active metabolite of Fx, treatment of human CRC cells resulted in plenty of living floating cells several hours after exposure, and induced apoptosis. In the present study, we investigated whether FuOH induced anchorage-dependent apoptosis, that is "anoikis", along with integrin signal suppression in human CRC cells. We found that cells exposed to 2.5 μM FuOH clearly showed anti-proliferative and apoptotic effects to DLD-1 cells, human CRC cells. FuOH treatment of DLD-1 cells led to an increase in anoikis-like changes represented by Calcein AM negative/ethidium homodimer-1 positive cell and living floating cells. Moreover, FuOH decreased FAK activation, and altered integrin β1 expression and distribution after 6 h treatment. After 24 h, the cells decreased PPARγ expression and Akt activation and increased integrin β1 expression. Our findings suggested that FuOH can induce anoikis in CRC cells through suppression of integrin signals in human CRC cells.

Topics: Allyl Compounds; Anoikis; Antineoplastic Agents, Phytogenic; beta Carotene; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Curcumin; Dietary Supplements; Focal Adhesion Kinase 1; Gene Expression Regulation, Neoplastic; Humans; Integrin beta1; Isothiocyanates; Lipids; PPAR gamma; Sulfides; Sulfoxides

Cancer survivors are motivated to change lifestyle following diagnosis, but studies investigating the outcomes are scarce. The purpose of this study was to examine the associations between antioxidant supplementation and quality of life (QoL) in stage-II colorectal cancer survivors. Four-hundred-fifty-three survivors were enrolled from the North Carolina Cancer Registry from 2009 to 2011. Interview data on demography, treatment, health behaviors, and QoL were collected at diagnosis, and at 12 and 24 mo post-diagnosis. Antioxidant supplementation was self-reported as use of selenium, zinc, beta-carotene, vitamin A, vitamin E, or vitamin C at baseline. Two-hundred-sixty-one subjects completed the 24-mo interview. After adjusting for multiple confounders, there was no association between antioxidant use and the Functional Assessment of Cancer Treatment-Colorectal [β = 1.41; 95% confidence interval (CI): -2.48, 5.30] or the medical outcomes 12-item short form (physical composite score: β = 0.84; 95% CI: -1.39, 3.07; mental composite score: β = -0.61; 95% CI: -2.65, 1.43). This study revealed no benefit of antioxidant use among survivors, possibly explained by a limited sample size of antioxidant users. More prospective studies are necessary to assess the benefits of antioxidants.

Topics: Aged; Antioxidants; beta Carotene; Cancer Survivors; Colorectal Neoplasms; Dietary Supplements; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Quality of Life; Selenium; Vitamins

The associations between specific carotenoid intake and colorectal cancer risk remain inconsistent. The aim of this study was to examine the association between specific dietary carotenoid intake with colorectal cancer risk in Chinese adults.. From July 2010 to October 2013, 845 eligible colorectal cancer cases and 845 frequency-matched controls (age and sex) completed in-person interviews. A validated food frequency questionnaire was used to estimate dietary intake. Multivariate logistical regression models were used to calculate the odds ratio (OR) and 95% confidence intervals (95% CIs) of colorectal cancer risk after adjusting for various confounders.. A strong inverse association was found between β-cryptoxanthin intake and colorectal cancer risk. Compared with the lowest quartile, the highest quartile intake showed a risk reduction of 77% (OR 0.23, 95% CI 0.17-0.33, P trend < 0.01) after adjustment for various confounding variables. The inverse associations were also observed for α-carotene (OR 0.50, 95% CI 0.37-0.68, P trend < 0.01), β-carotene (OR 0.67, 95% CI 0.49-0.91, P trend < 0.01), and lycopene (OR 0.51, 95% CI 0.37-0.70, P trend < 0.01). There was no statistically significant association between lutein/zeaxanthin intake and colorectal cancer risk. These findings were consistent across cancer site, sources of controls, and smoking status. The inverse associations between dietary α-carotene, β-cryptoxanthin, and lycopene intake and colorectal cancer risk were found in both males and females, while inverse associations between β-carotene intake and colorectal cancer risk were only observed in males.. Consumption of α-carotene, β-carotene, β-cryptoxanthin, and lycopene was inversely associated with colorectal cancer risk. No significant association was found between lutein/zeaxanthin intake and colorectal cancer risk.

Topics: Adult; Aged; Asian People; beta Carotene; Carotenoids; Case-Control Studies; China; Colorectal Neoplasms; Cryptoxanthins; Diet; Female; Humans; Life Style; Logistic Models; Lutein; Lycopene; Male; Middle Aged; Multivariate Analysis; Risk Factors; Socioeconomic Factors; Surveys and Questionnaires; Zeaxanthins

We have recently applied the technique of drop coating deposition Raman (DCDR) spectroscopy for colorectal cancer (CRC) detection using blood plasma. The aim of this study was to develop a more convenient and stable method based on blood plasma for noninvasive CRC detection. Significant differences are observed in DCDR spectra between healthy (n = 105) and cancer (n = 75) plasma from 15 CRC patients and 21 volunteers, particularly in the spectra that are related to proteins, nucleic acids, and β-carotene. The multivariate analysis principal components analysis and the linear discriminate analysis, together with leave-one-out, cross validation were used on DCDR spectra and yielded a sensitivity of 100% (75/75) and specificity of 98.1% (103/105) for detection of CRC. This study demonstrates that DCDR spectroscopy of blood plasma associated with multivariate statistical algorithms has the potential for the noninvasive detection of CRC.

Topics: beta Carotene; Case-Control Studies; Colorectal Neoplasms; Discriminant Analysis; Humans; Neoplasm Proteins; Nucleic Acids; Principal Component Analysis; Spectrum Analysis, Raman

Colorectal cancer is the third most common cancer worldwide. Diet has been hypothesized as involved in colorectal cancer etiology, but few studies on the influence of total dietary antioxidant intake on colorectal cancer risk have been performed.. We investigated the association between colorectal cancer risk and the total antioxidant capacity (TAC) of the diet, and also of intake of selected antioxidants, in 45,194 persons enrolled in 5 centers (Florence, Naples, Ragusa, Turin and Varese) of the European Prospective Investigation into Cancer and Nutrition (EPIC) Italy study. TAC was estimated by the Trolox equivalent antioxidant capacity (TEAC) assay. Hazard ratios (HRs) for developing colorectal cancer, and colon and rectal cancers separately, adjusted for confounders, were estimated for tertiles of TAC by Cox modeling, stratifying by center.. Four hundred thirty-six colorectal cancers were diagnosed over a mean follow-up of 11.28 years. No significant association between dietary TAC and colorectal cancer incidence was found. However for the highest category of TAC compared to the lowest, risk of developing colon cancer was lower (HR: 0.63; 95% CI: 0.44-0.89, P trend: 0.008). By contrast, increasing TAC intake was associated with significantly increasing risks of rectal cancer (2nd tertile HR: 2.09; 95%CI: 1.19-3.66; 3rd tertile 2.48 95%CI: 1.32-4.66; P trend 0.007). Intakes of vitamin C, vitamin E, and ß-carotene were not significantly associated with colorectal cancer risk.. Further prospective studies are needed to confirm the contrasting effects of high total antioxidant intake on risk of colon and rectal cancers.

Topics: Adult; Anthropometry; Antioxidants; Ascorbic Acid; beta Carotene; Chromans; Colorectal Neoplasms; Diet; Feeding Behavior; Female; Follow-Up Studies; Humans; Italy; Life Style; Male; Middle Aged; Nutrition Assessment; Proportional Hazards Models; Prospective Studies; Risk Factors; Vitamin E

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

To investigate the associations between serum concentrations of carotenoids and the presence of colorectal polyps and cancers in Japanese using a cross-sectional study.. 893 subjects who underwent colorectal endoscopy between 2001 and 2002 provided serum samples and information on lifestyle factors. Serum concentrations of six carotenoids were compared among patients with polyps, cancers, and controls.. In males, high serum zeaxanthin was associated with decreased rates of polyps [odds ratio (OR) = 0.48, 95 % confidence interval (CI) 0.27-0.87] and cancer (OR = 0.35, 95 % CI 0.12-1.06), adjusting for age, body mass index, serum cholesterol, smoking status, and alcohol intake. In females, zeaxanthin (OR = 0.25, 95 % CI 0.07-0.82), lutein (OR = 0.30, 95 % CI 0.10-0.94), alpha-carotene (OR = 0.30, 95 % CI 0.10-0.90), and beta-carotene (OR = 0.27, 95 % CI 0.09-0.85) showed significant inverse associations with cancer development. These associations were consistent with findings of inverse associations between the ingestion of green-yellow vegetables (OR = 0.44, 95 % CI 0.23-0.84), carrots and pumpkins (OR = 0.46, 95 % CI 0.25-0.86), and fruits (OR = 0.53, 95 % CI 0.30-0.94) and polyp in males, and between carrots and pumpkins (OR = 0.30, 95 % CI 0.09-0.99), legumes (OR = 0.14, 95 % CI 0.04-0.44), and seaweed (OR = 0.23, 95 % CI 0.07-0.75) and cancer development in females.. These results provide further support for the protective effects of carotenoids contained in green-yellow vegetables and fruits against colorectal neoplasm in Japanese.

Topics: Aged; beta Carotene; Carotenoids; Colorectal Neoplasms; Endoscopy; Female; Fruit; Humans; Japan; Lutein; Male; Middle Aged; Polyps; Risk Factors; Vegetables; Xanthophylls; Zeaxanthins

β,β-Carotene 15,15'-monooxygenase (BCMO1) converts β-carotene to retinaldehyde. Increased β-carotene consumption is linked to antitumor effects. Retinoic acid reduces the invasiveness in cancer, through inhibition of matrix metalloproteinases (MMPs). In our studies of a mouse model that develops intestinal tumors after low dietary folate, we found reduced BCMO1 expression in normal preneoplastic intestine of folate-deficient tumor-prone mice.. Our goal was to determine whether BCMO1 expression could influence transformation potential in human colorectal carcinoma cells, by examining the effect of BCMO1 modulation on cellular migration and invasion, and on expression of MMPs.. LoVo colon carcinoma cells were transfected with BCMO1 small interfering RNA (siRNA) or scrambled siRNA. Migration and invasion were measured, and the expression of BCMO1, MMP7, and MMP28 was assessed by quantitative reverse-transcriptase polymerase chain reaction. These variables were also measured after treatment of cells with retinoic acid, 5-aza-2'-deoxycytidine, folate-depleted/high-methionine medium, and β-carotene.. Retinoic acid decreased the migration, invasion, and expression of MMP28 mRNA. Transfection of cells with BCMO1 siRNA inhibited BCMO1 expression, enhanced migration and invasion, and increased expression of MMP7 and MMP28. 5-Aza-2'-deoxycytidine decreased, whereas folate-depleted/high-methionine medium increased invasiveness. β-Carotene increased BCMO1 expression and reduced invasiveness with a decrease in expression of MMP7 and MMP28.. Inhibition of BCMO1 expression is associated with increased invasiveness of colon cancer cells and increased expression of MMP7 and MMP28. β-Carotene can upregulate BCMO1 and reverse these effects. These novel associations suggest a critical role for BCMO1 in cancer and provide a mechanism for the proposed antitumor effects of β-carotene.

Topics: beta Carotene; beta-Carotene 15,15'-Monooxygenase; Cell Line, Tumor; Colon; Colorectal Neoplasms; Folic Acid; Gene Expression Regulation, Enzymologic; Humans; Intestinal Mucosa; Intestines; Matrix Metalloproteinase 7; Matrix Metalloproteinases, Secreted; RNA, Messenger; RNA, Small Interfering; Tretinoin; Up-Regulation

Previous cohort studies examining the association of serum antioxidant levels and risk of colorectal cancer have used a single (baseline) measurement only. In the present study, we assessed the association of serum levels of eight antioxidant nutrients in relation to risk of colorectal cancer, using repeated measurements.. Data on a subsample of women in the Women's Health Initiative with repeated measurements of serum retinol, α-carotene, β-carotene, β-cryptoxanthin, lutein+zeaxanthin, lycopene, α-tocopherol and γ-tocopherol during follow-up were included in the analysis. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs).. Among 5477 women with baseline serum antioxidant values, 88 incident cases of colorectal cancer were identified over a median follow-up time of 12 years. Serum antioxidants measured at baseline generally showed no association with risk of colorectal cancer, although serum β-carotene at baseline showed a non-significant inverse association with colon cancer alone. Furthermore, using the repeated measurements of β-carotene, the average of all measurements was inversely associated with risk of both colorectal and colon cancer: HRs for highest vs lowest tertile 0.54, 95% CI 0.31-0.96, and 0.47, 95% CI 0.25-0.88, respectively. No associations were seen with other antioxidant nutrients in the repeated measure analyses.. In this study, baseline levels of antioxidant nutrients were not associated with risk of colorectal or colon cancer; however, using repeated measures, a relatively high serum level of β-carotene (average of all measurements) was inversely associated with risk of colon and colorectal cancer in postmenopausal women.

Topics: Aged; Antioxidants; beta Carotene; Carotenoids; Colonic Neoplasms; Colorectal Neoplasms; Female; Humans; Incidence; Middle Aged; Nutrition Assessment; Nutritional Status; Proportional Hazards Models; Risk Factors; Tocopherols; Vitamin A; Women's Health

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

Topics: Aged; alpha-Tocopherol; beta Carotene; Biomarkers, Tumor; Colorectal Neoplasms; Enzyme-Linked Immunosorbent Assay; Finland; Follow-Up Studies; Humans; Incidence; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Middle Aged; Prognosis; Retrospective Studies; Risk Factors; Time Factors

In vitro and in vivo studies have associated iron with both the initiation and promotional stages of carcinogenesis. We investigated whether iron was associated with colorectal cancer in a nested case-control study within the alpha-tocopherol, beta-carotene cancer prevention study cohort. Exposure was assessed at baseline, using a 276-item food frequency questionnaire and a fasting serum sample. The study included 130 colorectal cancer cases (73 colon cancers and 57 rectal cancers) and 260 controls. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Supplemental iron intake was only reported for 4 cases and 18 controls; therefore, we were unable to obtain meaningful results for this variable. Comparing the highest to the lowest quartiles, there was an inverse association between serum ferritin and colorectal cancer risk (OR = 0.4, 95% CI = 0.2-0.9) and a suggestion of an inverse association between dietary iron and colorectal cancer risk (OR = 0.4, 95% CI = 0.1-1.1). In addition, serum ferritin, serum iron and transferrin saturation were all inversely associated with colon cancer risk specifically (OR = 0.2, 95% CI = 0.1-0.7, p trend = 0.02; OR = 0.2, 95% CI = 0.1-0.9, p trend = 0.05; OR = 0.1, 95% CI = 0.02-0.5, p trend = 0.003, respectively), whereas serum unsaturated iron binding capacity was positively associated with colon cancer risk (OR = 4.7, 95% CI = 1.4-15.1, p trend = 0.009). In summary, we found a significant inverse association between several serum iron indices and colon cancer risk.

Topics: Adult; Aged; alpha-Tocopherol; Anticarcinogenic Agents; beta Carotene; Case-Control Studies; Colorectal Neoplasms; Controlled Clinical Trials as Topic; Feeding Behavior; Female; Ferritins; Humans; Iron; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Risk Assessment; Risk Factors; Surveys and Questionnaires; Transferrin

Inactivating mutations in APC are thought to be early, initiating events in colorectal carcinogenesis. To gain insight into the relationship between diet and inactivating APC mutations, we evaluated associations between dietary factors and the occurrence of these mutations in a Dutch case-control study of sporadic colorectal adenomas (278 cases; 414 polyp-free controls). Direct-sequencing was used to screen adenomas for mutations in the mutation cluster region of APC; truncating mutations were detected in 161 (58%) of the adenomas. Red meat consumption was significantly differently related to polyps with truncating APC mutation (APC(+) polyps) compared to polyps without truncating APC mutation (APC(-) polyps) (highest vs. lowest tertile, odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.3-1.0). High intake of red meat and fat seemed to increase the risk of APC(-) polyps only (APC(+) vs. controls: red meat, OR = 1.0, 95% CI = 0.6-1.6; fat, OR = 1.1, 95% CI = 0.6-1.9; APC(-) vs. controls: red meat, OR = 1.8, 95% CI = 1.0-3.1; fat, OR = 1.9, 95% CI = 1.0-3.7). Intake of carbohydrates was inversely associated with both polyp groups, most noticeably with APC(-) polyps. Most other evaluated dietary factors were not distinctively associated with a specific APC status. None of the dietary factors was specifically associated with a particular type of truncating APC mutation. Our data suggest that red meat and fat may increase the risk of APC(-) polyps in particular, whereas carbohydrates may especially decrease the risk of APC(-) polyps. However, most examined dietary factors do not appear to be specifically associated with the occurrence of truncating APC mutations in colorectal adenomas but seem to affect both pathways equally.

Topics: Adenoma; Adult; Aged; Alcohol Drinking; Animals; Ascorbic Acid; beta Carotene; Calcium, Dietary; Case-Control Studies; Colorectal Neoplasms; Dairy Products; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Dietary Proteins; DNA, Neoplasm; Edible Grain; Energy Intake; Feeding Behavior; Female; Fishes; Folic Acid; Fruit; Genes, APC; Humans; Male; Meat; Middle Aged; Mutation; Netherlands; Poultry; Sequence Analysis, DNA; Vegetables

The effects of vitamins and beta-carotene on the risk of colorectal adenomas have not been fully investigated. Recent data suggest that smoking could modulate the effect of beta-carotene supplements on adenoma recurrence. We investigated the effect of dietary vitamins and beta-carotene on the risk of adenomas, and a potential interaction with smoking status as part of a case-control study of environmental factors associated with the risk of colorectal adenomas and cancers. We compared nutrient intakes in polyp-free controls (n = 427) and adenoma cases (n = 362) globally and using models stratified by smoking status, adjusted for age, sex, BMI, and energy and alcohol intakes. Folate and vitamins C and B-6 were inversely related to adenoma risk (P for trend = 0.005, 0.03, and 0.02, respectively), whereas vitamin D tended to be inversely associated with risk (P for trend = 0.05). There was a significant interaction between beta-carotene and smoking (P interaction = 0.04). In nonsmokers, beta-carotene was inversely associated with adenoma risk, especially that of colon adenomas [odds ratios (ORs) in low vs. high consumers and 95% CI 0.4 (0.2-0.9)], whereas in past or current smokers, beta-carotene was associated with a nonsignificant (P for trend = 0.19) increase in the risk of colon adenomas [corresponding OR = 1.9 (95% CI = 0.9-4.1)]. Our findings support a protective effect of folate and vitamins C and B-6 irrespective of smoking habits, and a protective effect of beta-carotene in nonsmokers only. They suggest an adverse effect of beta-carotene in smokers, who should be cautious about taking high doses of this micronutrient.

Topics: Adenoma; Adult; beta Carotene; Case-Control Studies; Colorectal Neoplasms; Female; Humans; Male; Middle Aged; Risk Factors; Risk Reduction Behavior; Smoking; Vitamins

To analyze the serum levels of retinoids and Leiden mutation in patients with esophageal, gastric, liver, pancreatic, and colorectal cancers.. The changes in serum levels of retinoids (vitamin A, alpha- and beta-carotene, alpha- and beta-cryptoxanthin, zeaxanthin, lutein) and Leiden mutation were measured by high liquid performance chromatography (HPLC) and polymerase chain reaction (PCR) in 107 patients (70 males/37 females) with esophageal (0/8), gastric (16/5), liver (8/7), pancreatic (6/4), and colorectal (30/21 including 9 patients suffering from in situ colon cancer) cancer. Fifty-seven healthy subjects (in matched groups) for controls of serum retinoids and 600 healthy blood donors for Leiden mutation were used.. The serum levels of vitamin A and zeaxanthin were decreased significantly in all groups of patients with gastrointestinal (GI) tumors except for vitamin A in patients with pancreatic cancer. No changes were obtained in the serum levels of alpha- and beta-carotene, alpha- and beta-cryptoxanthin, zeaxanthin, lutein in patients with GI cancer. The prevalence of Leiden mutation significantly increased in all groups of patients with GI cancer.. Retinoids (as environmental factors) are decreased significantly with increased prevalence of Leiden mutation (as a genetic factor) in patients before the clinical manifestation of histologically different (planocellular and hepatocellular carcinoma, and adenocarcinoma) GI cancer.

Topics: Adult; Aged; beta Carotene; Colorectal Neoplasms; Esophageal Neoplasms; Factor V; Female; Humans; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Point Mutation; Retinoids; Stomach Neoplasms; Vitamin A; Xanthophylls; Zeaxanthins

Topics: Adenomatous Polyposis Coli; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Bias; Chemoprevention; Colorectal Neoplasms; Humans; Incidence; Randomized Controlled Trials as Topic; Risk; Survival Analysis; Treatment Outcome; Vitamin E

Epidemiologic studies found that high tomato intakes reduce the risk of colorectal cancers. This beneficial effect is assumed to be caused by high intakes of lycopene, a carotenoid with strong antioxidant activity that is present predominantly in tomatoes.. We assessed the relation between plasma lycopene concentrations and colorectal adenomas, the precursors for most colorectal cancers. In addition, the concentrations of 2 other antioxidants, beta-carotene and alpha-tocopherol, were measured.. White subjects undergoing a complete colonoscopy were included in the study (73 with adenomas, 63 without any polyps, and 29 with hyperplastic polyps). A detailed dietary history and information on alcohol consumption and smoking habits were collected from all subjects. Plasma lycopene, beta-carotene, and alpha-tocopherol concentrations were measured by using HPLC.. Patients with adenomas and control subjects without polyps did not differ significantly in body mass index; intakes of energy, fat, protein, carbohydrates, fiber, beta-carotene, and alcohol; or prevalence of smoking, but patients with adenomas were slightly older. The median plasma lycopene concentration was significantly lower in the adenoma group than in the control group (-35%; P = 0.016). The median plasma beta-carotene concentration also tended to be lower in the adenoma group (-25.5%), but the difference was not significant. In the multiple logistic regression, only smoking (odds ratio: 3.02; 95% CI: 1.46, 6.25; P = 0.003) and a plasma lycopene concentration < 70 microg/L (odds ratio: 2.31; 1.12, 4.77; P = 0.023) were risk factors for adenomatous polyps. Patients with hyperplastic polyps did not differ significantly from control subjects in any variable.. Our findings support the hypothesis that lycopene contributes to the protective effect of high tomato intakes against the risk of colorectal adenomas.

Topics: Adenoma; Adult; Age Factors; Aged; alpha-Tocopherol; Antioxidants; beta Carotene; Carotenoids; Case-Control Studies; Chromatography, High Pressure Liquid; Colonic Polyps; Colorectal Neoplasms; Diet; Female; Humans; Logistic Models; Lycopene; Male; Middle Aged; Risk Factors

It has been postulated that high intakes of animal fat and protein and low intakes of fiber, calcium, and antioxidants increase the risk of colorectal cancer. Whether specific types of protein such as that from red meat are important, and whether vegetables might be key protective factors will also be considered in this study. Dietary intake over the past year was studied according to the diet history method by means of a case-control study in 184 cases and matched controls. After adjustment for energy, relative weight, and social class, no associations were found for fat or protein in comparison with either control group. Unexpectedly, carbohydrate intake was inversely related with adenoma risk, the RR being 0.29 (0.10-0.81) for quintile 5 versus 1 in comparison with hospital controls. None of the antioxidants showed a significant protective effect except beta-carotene intake in comparison with hospital controls, the RR being 0.24 (0.11-0.50) for the highest versus the lowest quintile. There was, however, a statistically significant positive association between adenomas and meat consumption with the RR for the highest versus the lowest quintile. There was, however, a statistically significant positive association between adenomas and meat consumption with the RR for the highest versus the lowest quintile of intake being 3.6 (1.7-7.5) in comparison with hospital controls and 4.4 (1.6-12.1) in comparison with population controls. Our data support the protective role for carbohydrate intake and of beta-carotene intake in the etiology of colorectal adenomas and show a strong increased risk for developing adenomas in those with high meat intake.

Topics: Adenoma; Aged; Aged, 80 and over; Antioxidants; beta Carotene; Case-Control Studies; Colorectal Neoplasms; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Female; Humans; Male; Meat; Middle Aged

A long-term sufficient intake of fruits and vegetables reduces significantly the risk of gastric and colorectal carcinoma. It is anticipated that natural antioxidants are involved in this effect in addition to other substances. The aim of this study was to determine levels of vitamins A, C and E, as well as beta-carotene, selenium, zinc and copper in blood of 249 patients with precancerous lesions (atrophic gastritis, gastric hyperplastic polyp, gastric, colonic and rectal adenoma, chronic ulcerative colitis) and in 96 individuals with gastric, colonic or rectal carcinoma and to compare these levels with the values of a control group of 130 healthy individuals. We have found that the frequency of average values of analyzed micronutrients in precancerous groups was decreasing in the order vit C > vit E/vit A > Se > beta-car. The average levels of vitamins and beta-carotene were significantly reduced in all carcinoma groups, while selenium level showed a decrease only in the gastric carcinoma group. Copper level was elevated in the ulcerative colitis group and in all groups with carcinoma. The results indicate a frequent insufficient saturation of organism by natural antioxidants in groups with precancerous lesions and carcinomas of stomach and colorectum. Therefore, it is necessary to increase the general consumption of fruits and vegetables in Slovakia as a part of primary prevention of malignant diseases in these organs. Chemoprevention may be recommended in individuals with precancerous lesions.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Case-Control Studies; Colorectal Neoplasms; Copper; Diet; Female; Humans; Male; Middle Aged; Precancerous Conditions; Selenium; Slovakia; Stomach Neoplasms; Vitamin A; Vitamin E; Zinc

Optimal saturation of organism by micronutrients--vitamins and trace elements--has a significant inhibitory effect on the origin and development of malign diseases.. The aim of the study was to investigate the blood levels of A, C and E vitamins, Beta-carotene, zinc, and selenium in 249 patients with precanceroses (atrophic gastritis, hyperplastic polyp of the stomach, adenomas of the stomach and colorectum, ulcerative colitis), 96 patients with carcinoma of the stomach or colorectum, and to compare them with a control group of 130 people.. We have discovered the frequency of decreased average levels of micronutrients in patients with precanceroses as follows: vitamin C > vitamins E and A > selenium > beta carotene. In all groups of patients with carcinoma the average levels of vitamins and Beta-carotene were significantly decreased, the level of selenium has decreased only in the group of gastric carcinoma. The copper level was increased in the group of ulcerative colitis and in all groups with carcinoma.. The results indicate that in the primary prevention of these malign diseases it is necessary to improve the levels of the presented micronutrients in the population of the Slovak Republic by increasing the intake of fruit, vegetables and other sources of nutrition, the secondary prevention in persons with precanceroses requires an appropriate intermittent supplementation of micronutrients (chemoprevention). (Tab. 3, Ref. 24.)

Topics: Adult; beta Carotene; Colorectal Neoplasms; Female; Humans; Male; Micronutrients; Middle Aged; Precancerous Conditions; Selenium; Stomach Neoplasms; Vitamins; Zinc

Using data from a case-control study conducted between 1985 and 1992 in northern Italy on 828 cases of colon cancer, 498 cases of rectal cancer and 2,024 controls in hospital for acute, non-neoplastic, non-digestive tract disorders, we estimated the percent population attributable risk (PAR) for colorectal cancer in relation to beta-carotene, vitamin C (as markers of a diet rich in fruit and vegetables), red meat and seasoning fat intake, daily meal frequency and family history of the disease. On the basis of multivariate odds ratios, adjusted for total calorie intake, a low intake of beta-carotene accounted for 39% of all the cases and a low intake of vitamin C for 14%. These two micronutrients together explained 43% of all colorectal cancer cases in this population. A high frequency of intake of red meat consumption explained 17% of all cases, and a high score of seasoning fats 4%. A higher daily meal frequency was responsible for 13% of the cases, and these 5 dietary factors together explained 63% of colorectal cancer cases in this population. Family history of colorectal cancer accounted for 4% of all cases. These estimates were similar for colon and rectal cancers separately, in males and females, and in younger and elderly subjects, except for seasoning fats and family history, whose PARs were apparently greater for colon cancer and at younger age. Thus, even though available dietary data were limited in several aspects, and the PAR estimates were based on somewhat arbitrary assumptions regarding the exposure distribution, about two-thirds of all colorectal cancers in this population could be explained in terms of a few risk factors or risk indicators considered. This would correspond to the avoidance of a large proportion of the over 18,000 deaths from colorectal cancer registered per year in the whole of Italy.

Topics: Adult; Age Factors; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Colorectal Neoplasms; Diet; Energy Intake; Feeding Behavior; Female; Humans; Italy; Male; Middle Aged; Multivariate Analysis; Risk Factors; Sex Factors; Surveys and Questionnaires

Topics: Animals; beta Carotene; Colorectal Neoplasms; Diet; Dietary Fiber; Humans; Mice; Mice, Knockout

The relationship between estimated intake of selected micronutrients and the risk of colorectal cancer was analysed using data from a case-control study conducted in northern Italy. The study was based on 828 patients with colon cancer, 498 with rectal cancer and 2,024 controls in hospital for acute, non-neoplastic, non-digestive tract diseases. Relative risks (RRs) of intake quintiles were computed after allowance for age, sex and other major potential confounding factors, including an estimate of total energy intake. No apparent trend in risk across intake quintiles was evident for retinol, vitamin D, methionine and calcium. For beta-carotene, ascorbic acid, vitamin E and folate there was a trend of a protective effect with increasing consumption: the RR for the highest versus the lowest quintile was 0.32 for beta-carotene, 0.40 for ascorbic acid, 0.60 for vitamin E and 0.52 for folate. These inverse associations were similar for colon and rectal cancer, and consistent across strata of sex and age. When simultaneous allowance was made for all these micronutrients, besides other covariates, the only persistent protective effects were for beta-carotene (RR = 0.38 for the highest quintile) and ascorbic acid (RR = 0.52). Whether this reflects a specific, or stronger, effect of these micronutrients, rather than problems of collinearity between micronutrients or other limitations of the data, remains open to discussion. Still, this study suggests that specific micronutrients may exert an independent protective effect against colorectal carcinogenesis.

Topics: Adult; Age Factors; Aged; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Colorectal Neoplasms; Diet; Female; Folic Acid; Humans; Male; Middle Aged; Regression Analysis; Risk Factors; Sex Factors; Vitamin E

The organospecific, 1,2-dimethylhydrazine-induced murine tumor model was used to test the effects on tumor formation of the following dietary supplements: (1) ascorbic acid, 7% per weight; (2) alpha tocopherol, 1% per weight; (3) beta carotene, 1% per weight; and (4) canthazanthin, 1% per weight. Following a four-week dietary acclimation, a 16-week 1,2-dimethylhydrazine induction, and a four-week hiatus, the animals were killed, underwent autopsies, and tumor formation was recorded. The antioxidant supplements of ascorbic acid and alpha tocopherol resulted in a significant decrease in tumor formation when compared with control groups. In contrast, the beta carotene group showed no difference in tumor formation, and canthazanthin, a non-provitamin A carotenoid, resulted in an increase in tumor formation when compared with controls. In addition, the K-gel powder control diet (a carrier medium for alpha tocopherol acetate) had a significantly higher rate of tumor formation than the regular chow and placebo beadlet control diets. In sum, ascorbic acid and alpha tocopherol demonstrated a clear chemopreventive effect, whereas beta carotene had no effect, and canthazanthin appeared to function as a promoter in this organospecific tumor model.

Topics: 1,2-Dimethylhydrazine; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Canthaxanthin; Carotenoids; Colorectal Neoplasms; Dimethylhydrazines; Male; Rats; Vitamin E