beta-carotene and Adenoma

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 The following databases were searched for published and unpublished literature: Cochrane Library, MEDLINE, PreMEDLINE, CINAHL, EMBASE, Web of Science, and Biological Abstracts and Research Registers.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

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

The intra- and interindividual variations and season and center effects were estimated from a series of serum carotenoid concentrations in the Polyp Prevention Trial (PPT) participants.. Fasting blood was collected annually for 4 years in all 1905 participants, and a subcohort of 901 participants were selected within each (of eight) center(s), by gender and dietary arm of the study, for measurement of five major carotenoid peaks. Using variance of component methods, the variation in serum carotenoid concentrations about the underlying mean was partitioned into explanatory components attributed to various sources.. The contributions of the inter- and intraindividual variances to the overall variation in carotenoid concentrations were in the range of 61-70 and 20-35%, respectively, whereas center and center-by-season effects provided 2.6-9.5 and 0.2-1.4%, respectively. The highest percent (35%) of intraindividual variation was exhibited by lycopene, and the highest percent (70% apiece) of interindividual variation was exhibited by lutein/zeaxanthin and beta-carotene. Serum lycopene had the highest ratio of intra- to interindividual variation of 0.57, whereas lutein had the lowest ratio of 0.29. We estimate that the ratio of intra- to interindividual variance around the mean carotenoid concentration can be reduced greatly by collecting 3-4 compared to 1 blood measurement in large-scale trials like the PPT.. In the largest study of components of variation in individuals at high risk for colorectal cancer, the largest contributors to variation in serum carotenoid concentrations were intra- and interindividual effects followed by center and center-by-season effects.

Topics: Adenoma; beta Carotene; Carotenoids; Colonic Neoplasms; Cryptoxanthins; Diet; Female; Humans; Lutein; Lycopene; Male; Middle Aged; Neoplasm Recurrence, Local; Risk Factors; Seasons; Xanthophylls; Zeaxanthins

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

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

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

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

Pituitary adenomas comprise approximately 10-15% of intracranial tumors and result in morbidity associated with altered hormonal patterns, therapy and compression of adjacent sella turcica structures. The use of functional foods containing carotenoids contributes to reduce the risk of chronic diseases such as cancer and vascular disorders. In this study, we evaluated the influence of different concentrations of beta-carotene and lycopene on cell viability, colony formation, cell cycle, apoptosis, hormone secretion, intercellular communication and expression of connexin 43, Skp2 and p27(kip1) in ACTH-secreting pituitary adenoma cells, the AtT20 cells, incubated for 48 and 96 h with these carotenoids. We observed a decrease in cell viability caused by the lycopene and beta-carotene treatments; in these conditions, the clonogenic ability of the cells was also significantly decreased. Cell cycle analysis revealed that beta-carotene induced an increase of the cells in S and G2/M phases; furthermore, lycopene increased the proportion of these cells in G0/G1 while decreasing the S and G2/M phases. Also, carotenoids induced apoptosis after 96 h. Lycopene and beta-carotene decreased the secretion of ACTH in AtT20 cells in a dose-dependent manner. Carotenoids blocked the gap junction intercellular communication. In addition, the treatments increased the expression of phosphorylated connexin43. Finally, we also demonstrate decreased expression of S-phase kinase-associated protein 2 (Skp2) and increased expression of p27(kip1) in carotenoid-treated cells. These results show that lycopene and beta-carotene were able to negatively modulate events related to the malignant phenotype of AtT-20 cells, through a mechanism that could involve changes in the expression of connexin 43, Skp2 and p27(kip1); and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing's disease.

Topics: Adenoma; Adrenocorticotropic Hormone; Animals; Apoptosis; beta Carotene; Carotenoids; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Connexin 43; Cyclin-Dependent Kinase Inhibitor p27; Gap Junctions; Lycopene; Mice; Phosphorylation; Pituitary Neoplasms; S-Phase Kinase-Associated Proteins

Pituitary adenomas produce the chemokine stromal cell-derived factor (SDF-1α/CXCL12) and its receptor, CXCR4. A recent study indicated that CXCL12 and CXCR4 are concomitantly up-regulated in hypoxia. The objective of this study was to analyze the molecular mechanism of hypoxia-mediated CXCR4 up-regulation and assess the effect of pharmacological inhibition of CXCR4 by the receptor blocker, AMD3100, on pituitary function. CXCR4 expression in pituitary adenoma tissues was determined by a tissue microarray analysis of 62 pituitary adenoma samples. CXCR4 expression was significantly elevated and positively correlated with Knosp grade in pituitary adenomas (P < 0.005), and was higher in macroadenoma and growth hormone (GH)-producing adenomas. Pre-operative serum GH levels were significantly correlated with CXCR4 levels in the microarray (P < 0.0001). The relative expression of genes/gene categories that were modulated by up-regulated CXCL12/CXCR4 signaling was determined by a comparative transcriptome analysis of wild-type and CXCR4-knockdown cells in normoxia and hypoxia using the rat GH-producing and prolactin-producing pituitary adenoma cell line, GH3. Real-time reverse transcriptase-polymerase chain reaction analysis (RT-PCR) showed that CXCR4 mRNA expression in GH3 cells was increased by hypoxia (1% oxygen), and a cDNA microarray analysis revealed that inhibin β-C expression was diminished. siRNA-mediated CXCR4 knockdown blocked the hypoxia-induced decrease in inhibin β-C mRNA expression, as did inhibition of CXCR4 activity with AMD3100. An ELISA study demonstrated that GH secretion by wild-type GH3 cells was moderately enhanced by hypoxia and further potentiated by exposure to recombinant SDF-1α/CXCL12 protein. Conversely, hypoxia-induced GH secretion was reduced in CXCR4-silenced cells and in cells treated with the CXCR4 antagonist, AMD3100, notwithstanding the presence of SDF-1α/CXCL12 protein. These latter observations reflect the failure of hypoxia to suppress expression of inhibin β-C in cells deficient in CXCR4 or in which CXCR4 signaling was blocked. Together, these results indicate that the SDF-1α/CXCL12-CXCR4 signaling pathway interfaces with the classical endocrine pathway to up-regulate GH production via suppression of inhibin β-C. Because it blocks CXCR4 and prevents hypoxia-induced down-regulation of inhibin β-C expression, AMD3100 has promise as a molecular-targeting agent in the treatment of GH-producing adenomas.

Topics: Adenoma; Animals; Benzylamines; beta Carotene; Cell Hypoxia; Cell Line, Tumor; Chemokine CXCL12; Cyclams; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Growth Hormone; Heterocyclic Compounds; Humans; Middle Aged; Oligonucleotide Array Sequence Analysis; Pituitary Neoplasms; Rats; Receptors, CXCR4; RNA, Messenger; RNA, Small Interfering; Statistics as Topic

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

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

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

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

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

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

We have reported protective effects of dietary administration of a powder "CHRP" containing high amounts of beta-cryptoxanthin and hesperidin prepared from a Satsuma mandarin (Citrus unshiu Marc.) juice on azoxymethane (AOM)-induced rat aberrant crypt foci through suppression of crypt cell proliferation and/or induction of detoxifying enzymes. In the present study, we investigated the modifying effects of a commercial Satsuma mandarin (Citrus unshiu Marc.) juice (MJ) and those of MJ2 and MJ5, which were prepared from MJ and are richer in beta-cryptoxanthin and hesperidin than MJ, on the occurrence of colonic tumors induced by AOM in male F344 rats. Rats were given 2 weekly s.c. injections of AOM (20 mg/kg body weight) to induce colonic neoplasms. They also received MJ, MJ2, or MJ5 as a drinking water at night for 36 weeks, starting 1 week after the last dosing of AOM. AOM exposure produced colonic adenocarcinoma with an incidence of 69% and a multiplicity of 0.76 +/- 0.57/rat at week 38. MJ, MJ2, and MJ5 administration significantly reduced the frequency of colonic carcinoma [MJ: 35% (49% reduction), p < 0.02; MJ2: 20% (64% reduction), p = 0.0028; and MJ5: 15% (78% reduction), p < 0.00021] and multiplicity [MJ: 0.40 +/- 0.58 (47% reduction), p < 0.05; MJ2: 0.25 +/- 0.43 (67% reduction), p < 0.005; and MJ5: 0.15 +/- 0.36 (80% reduction), p < 0.001]. Also, the numbers of cancer cells positive for proliferative cell nuclear antigen (PCNA) and cyclin D1 in colonic tumors were lowered by these treatments. In addition, treatment with MJ, MJ2, or MJ5 significantly increased apoptotic index in colonic adenocarcinoma. These findings might suggest effective chemopreventive ability of MJs, especially MJ5, in colon tumorigenesis.

Topics: Adenocarcinoma; Adenoma; Animals; Anticarcinogenic Agents; Apoptosis; Azoxymethane; beta Carotene; Beverages; Carcinogens; Citrus; Colonic Neoplasms; Cryptoxanthins; Cyclin D1; Hesperidin; Male; Proliferating Cell Nuclear Antigen; Rats; Rats, Inbred F344; Xanthophylls

We determined whether intakes of the main dietary carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein plus zeaxanthin, and lycopene) and of vitamins A, C, and E were associated with the prevalence of colorectal adenomas among male and female members of a prepaid health plan in Los Angeles who underwent sigmoidoscopy (n = 488 matched pairs). Participants, ages 50-74 years, completed a 126-item semiquantitative food-frequency questionnaire and a non-dietary questionnaire from 1991 to 1993. In the univariate-matched analysis, alpha-carotene, beta-carotene (with and without supplements), beta-cryptoxanthin, lutein plus zeaxanthin, vitamin A (with and without supplements), and vitamin C (with and without supplements) were associated with a decreased prevalence of colorectal adenomas. After adjustment for intake of calories, saturated fat, folate, fiber, and alcohol, and for current smoking status, body mass index, race, physical activity, and use of nonsteroidal anti-inflammatory drugs, only beta-carotene including supplements was inversely associated with adenomas (odds ratio (OR), 0.6; 95% confidence interval (CI), 0.41.1; trend, P= 0.04; ORs compare highest to lowest quartiles0; vitamin C showed a weaker inverse association (OR, 0.8; 95% CI, 0.5-1.5; trend, P = 0.08); and the remaining compounds were no longer clearly associated with risk. After including beta-carotene with supplements and vitamin C simultaneously in the mutivariate model, the association of beta-carotene with supplements with adenomas was weakened (OR, 0.8; 95% CI, 0.5-1.3; trend P = 0.15), and vitamin C was no longer associated with risk. These data provide only modest support for a protective association of beta-carotene with colorectal adenomatous polyps.

Topics: Adenoma; Aged; Anticarcinogenic Agents; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Colonic Neoplasms; Cryptoxanthins; Diet; Feeding Behavior; Female; Humans; Los Angeles; Lutein; Lycopene; Male; Middle Aged; Multivariate Analysis; Prevalence; Rectal Neoplasms; Risk Factors; Sigmoidoscopy; Vitamin A; Vitamin E; Xanthophylls; Zeaxanthins

Selenium deficiency has been associated with cancer risk in several organs. This association was investigated in neoplasia of the colorectum.. A case-control study is reported with two patient series, colorectal cancer and colorectal adenomatous polyps, and a control group found to be free of colorectal neoplasia. Diagnosis was determined by colonoscopy and histologic review of suspected neoplasms. Serum drawn at the time of colonoscopy was subsequently assayed for selenium content, and quartiles based on selenium were defined. Crude and adjusted odds ratios with 95 percent confidence intervals for adenoma related to selenium were calculated, controlling for known or suspected risk factors including gender, age, race, body mass index, family history, tobacco use, alcohol consumption, serum beta carotene, serum alpha tocopherol, and serum ferritin.. There were 138 controls who had no neoplastic disease, 139 adenoma patients, and 25 cancer patients. For adenoma, comparing higher quartiles of selenium to the first (lowest selenium), the adjusted odds ratio for the second quartile was 1.7 (95 percent confidence interval, 0.8-3.7), the third quartile was 1.4 (0.7-3.2), and the fourth (highest selenium) quartile was 1.8 (0.9-4). The odds ratios for cancer patients were 0.8 for the second quartile, 1 for the third quartile, and 1.7 for the fourth quartile.. No trend could be detected toward a protective effect of higher levels of serum selenium for colonic benign or malignant tumors.

Topics: Adenoma; Adenomatous Polyps; Adult; Age Factors; Aged; Aged, 80 and over; Alcohol Drinking; beta Carotene; Body Mass Index; Carotenoids; Case-Control Studies; Colonic Neoplasms; Colonic Polyps; Colonoscopy; Female; Ferritins; Humans; Male; Middle Aged; Odds Ratio; Racial Groups; Rectal Neoplasms; Risk Factors; Selenium; Sex Factors; Smoking; Vitamin E

Colonic crypt cell proliferation is used as an indicator of risk of colorectal carcinoma. Subjects with adenomatous polyps and cancer have an increased cell proliferation and a shift of the proliferative zone towards the apex of the crypt. Epidemiological and in vitro studies have confirmed a link between vitamins A, E, C, beta-carotene, and colorectal cancer. In vitro bromodeoxyuridine immunohistochemical technique was used to assess the effect of daily oral supplementation with vitamin E (160 mg), vitamin C (750 mg), or beta-carotene (9 mg) on the colonic crypt cell proliferation in patients with adenomatous polyps (n = 40) compared with normal subjects with no colonic disease (n = 20). The patients were given supplementation for one month and colonic biopsy specimens were taken before and at the end of the trial. Patients with adenomatous polyps had a significantly higher mean labelling index per cent than controls (p < 0.001). Vitamin C or beta-carotene supplementation, however, significantly reduced the total proliferation (p < 0.005) whereas vitamin E supplementation had no effect on the colonic crypt cell proliferation. beta-carotene reduced cell proliferation at the base of the crypt only. Vitamin C reduced cell proliferation in all the crypt compartments from the apex to the base to those values seen in age and sex matched controls. These findings indicate that prolonged supplementation with vitamin C may reduce the recurrence of adenomatous polyps.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Antioxidants; beta Carotene; Carotenoids; Cell Division; Female; Humans; Immunohistochemistry; Intestinal Mucosa; Intestinal Polyps; Male; Middle Aged; Vitamins