Dietary Intakes of Retinol,Carotenes, Vitamin C,and Vitamin E and Colorectal Cancer Risk: The Fukuoka Colorectal Cancer Study

It has long been a matter of interest whether antioxidant vitamins are protective against colorectal cancer as well as human cancers in general, but epidemiological evidence is inconclusive. We investigated associations of dietary intakes of retinol and antioxidant vitamins with colorectal cancer risk in 816 incident cases of histologically confirmed colorectal cancer and 815 controls randomly selected for the Fukuoka colorectal cancer study in Japan. Dietary intakes were assessed by a PC-assisted interview regarding 148 food items. Statistical adjustment was made for body mass index, physical activity, calcium, and n-3 fatty acid intake and other factors. Retinol intake was significantly, inversely associated with colorectal cancer risk; the odds ratio for the highest vs. lowest was 0.55 (95% CI: 0.35, 0.88; P _trend = 0.01) in women, but a modest increase in the risk was observed among men with the highest intake of retinol. Liver was the major source of retinol intake and showed similar associations with colorectal cancer risk in men and women. Intake of carotenes, vitamin C, and vitamin E were not related to colorectal cancer risk in either men or women. The study did not support a hypothesis that dietary intake of antioxidant vitamins is protective in the development of colorectal cancer.     

Folate, vitamin B6, multivitamin supplements, and colorectal cancer risk in women

The authors evaluated associations between intakes of folate and vitamin B(6) and colorectal cancer risk among women enrolled in a randomized trial on aspirin and vitamin E in disease prevention. At baseline (1992-1995), 37,916 US women aged >or=45 years who were free of cancer and cardiovascular disease provided dietary information. During an average of 10.1 years of follow-up (through February 20, 2004), 220 colorectal adenocarcinoma cases were documented. Total folate and vitamin B(6) intakes were not significantly associated with the risk of colorectal cancer. However, dietary intakes of folate and vitamin B(6) were significantly inversely associated with colorectal cancer risk among women who were not taking supplements containing folate and vitamin B(6). Multivariable relative risks among women in the highest quintiles of intake versus the lowest were 1.16 (95% confidence interval (CI): 0.76, 1.79) for total folate, 1.14 (95% CI: 0.77, 1.69) for total vitamin B(6), 0.46 (95% CI: 0.26, 0.81) for dietary folate, and 0.69 (95% CI: 0.41, 1.15) for dietary vitamin B(6). The use of multivitamin supplements was not related to colorectal cancer risk. These findings suggest that higher dietary intakes of folate and vitamin B(6) may reduce the risk of colorectal cancer in women. An alternative explanation is that other factors related to dietary intakes of folate and vitamin B(6) account for the inverse associations.     

Low intake of vitamin B-6 is associated with increased risk of colorectal cancer in Japanese men

We investigated the association of dietary intakes of folate, vitamin B-6, vitamin B-12, and methionine with the risk of colorectal cancer in a large prospective cohort study of middle-aged Japanese men and women. A total of 81,184 subjects (38,107 men and 43,077 women) who participated in the Japan Public Health Center-based Prospective Study were followed from 1995-1998 to the end of 2002, during which 526 cases of colorectal cancer (335 men, 191 women) were newly identified. Dietary intake of nutrients was calculated using a 138-item self-administered FFQ. We observed a significant inverse association between vitamin B-6 intake and colorectal cancer in men. Compared with the lowest quartile, the multivariate hazard ratio (95% [CI]) in the highest quartile of intake was 0.69 (0.48-0.98) (P(trend) = 0.03). Men who consumed 150 g/wk alcohol or more had twice the risk of colorectal cancer of those who drank less in the lowest quartile of vitamin B-6 intake, but risk due to alcohol intake was not higher in the highest quartile of vitamin B-6 intake. Vitamin B-6 intake and colorectal cancer were not associated in women. Folate and methionine intakes were not associated with colorectal cancer risk in men or women, but colorectal cancer risk tended to increase (P(trend) = 0.05) with increasing intake of vitamin B-12 in men. Our results support previous evidence that low vitamin B-6 intake is associated with an increased risk of colorectal cancer. In particular, a higher intake of vitamin B-6 appears beneficial in men with higher alcohol intake.     

Calcium and vitamin D intake and risk of colorectal cancer: the Multiethnic Cohort Study

The associations of intakes of calcium and vitamin D with colorectal cancer risk were examined in the Multiethnic Cohort Study (Hawaii and Los Angeles, California). In 1993-1996, 85,903 men and 105,108 women aged > or =45 years completed a quantitative food frequency questionnaire. A total of 2,110 incident cases of colorectal cancer (1,138 in men and 972 in women) were identified through December 31, 2001. Cox proportional hazards models were used to calculate multivariate-adjusted relative risks and 95% confidence intervals. Total calcium intake (from foods and supplements) was inversely associated with colorectal cancer risk in both men (highest quintile vs. lowest: relative risk (RR) = 0.70, 95% confidence interval (CI): 0.52, 0.93; p for trend = 0.006) and women (RR = 0.64, 95% CI: 0.50, 0.83; p for trend = 0.003). The inverse association was also seen for total vitamin D intake in men (RR = 0.72, 95% CI: 0.51, 1.00; p for trend = 0.03) but not in women. Intake of dairy products was inversely associated with colorectal cancer risk, especially among nonusers of supplemental calcium (men: RR = 0.77, 95% CI: 0.59, 1.01; women: RR = 0.66, 95% CI: 0.49, 0.89). The findings support the hypothesis of protective roles for calcium, vitamin D, and dairy products in the risk of colorectal cancer.     

Risk of colorectal cancer from alcohol consumption at lower vitamin intakes. A hospital-based case-control study in Poland.

The purpose of the study was to assess the relation between the simultaneous exposure to alcohol and consumption of micronutrients that have protective properties against colorectal cancer. A hospital-based case-control study of colorectal cancer was carried out between January 1998 and November 1999 at the University Hospital in Krakow, Poland. In total, 180 incident cases of colorectal cancer, confirmed by histopathology, were recruited and an equal number of controls, individually matched by gender and age (+/-5 y), were chosen amongst patients with no history of cancer. A food-frequency questionnaire for 148 food items, combined with the quantity of foods eaten, was used to assess the normal dietary pattern. The data confirmed the reported inverse association between the intake of retinol, thiamine, or antioxidant micronutrients (vitamins C, E) and the occurrence of colorectal cancer. Alcohol intake was found to be an important risk factor for this cancer site, and the risk escalated in parallel with increased intake of retinol, carotene, vitamins C and E, but with high consumption of alcohol ran a noticeably high risk of colorectal cancer (OR= 6.79; 95% CI: 2.08-22.18). The risk was markedly lower, however, among alcohol drinkers who reported a high intake of micronutrients (OR = 1.35; 95% CI: 0.39-4.67). The data suggest that a combination of high consumption of alcohol and low intake of retinol and antioxidant vitamins may considerably increase the risk of colorectal cancer.     

Intakes of calcium and vitamin D and risk of colorectal cancer in women

In vivo and in vitro studies have suggested a protective role of calcium and vitamin D in the development of colorectal cancer. However, epidemiologic data have been inconclusive. The authors prospectively assessed intakes of calcium and vitamin D in relation to risk of colorectal cancer in a large, prospective, female cohort from the US Women's Health Study. In 1993, 39,876 women aged > or = 45 years and free of cardiovascular disease and cancer were enrolled in the study. During an average follow-up of 10 years, 223 of 36,976 women eligible for the present study developed colorectal cancer. Intakes of calcium and vitamin D from dietary sources and supplements were assessed with a baseline food frequency questionnaire. Cox proportional hazards regression was used to estimate relative risks and 95% confidence intervals. Intakes of total calcium and vitamin D were not associated with risk of colorectal cancer; multivariate relative risks comparing the highest with the lowest quintile were 1.20 (95% confidence interval: 0.79, 1.85; p for trend = 0.21) for total calcium and 1.34 (95% confidence interval: 0.84, 2.13; p for trend = 0.08) for total vitamin D. Intakes of both nutrients from specific types of sources, including diet and supplements, were also not significantly associated with colorectal cancer risk. Data provide little support for an association of calcium and vitamin D intake with colorectal cancer risk.     

High dietary iron and copper and risk of colorectal cancer: a case-control study in Burgundy, France

Several hypotheses have been proposed for colorectal carcinogenesis, including formation of free radicals. A case-control study compared nutrient intake in 171 colorectal cancer cases versus 309 general population controls, using a detailed face-to-face food history questionnaire. A food composition table enabled us to determine the mean composition of the diet in macro- and micronutrients. Dietary intakes were separately categorized into quartiles by gender. Logistic regression models were adjusted for age, sex, energy, exercise, and body mass index. High energy, copper, iron, and vitamin E intakes were associated with an overall increased risk of colorectal cancer. The odds ratios associated with the fourth quartile of intake were 2.3 (95% confidence interval, 1.3-4.0), 2.4 (1.3-4.6), 2.2 (1.1-4.7), and 1.8 (1.0-3.4) for energy, copper, iron, and vitamin E, respectively. There were no significant associations with dietary fiber, folate, calcium, or antioxidant vitamins other than vitamin E. These findings regarding iron and copper suggest that free radicals play an important role in colorectal carcinogenesis, while the findings regarding vitamin E are so far unexplained.     

Dietary and serum alpha-tocopherol,beta-carotene and retinol,and risk for colorectal cancer in male smokers

OBJECTIVE: To study the association between dietary and serum antioxidant vitamins and carotenoids and risk for colorectal cancer in male smokers. DESIGN: 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. SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SPONSORSHIP: The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study was supported by a contract with the US National Cancer Institute (N01-CN-45165).     

Dietary B vitamin and methionine intakes and breast cancer risk among Chinese women

Methionine, folate, vitamin B(6), vitamin B(12), niacin, and riboflavin intakes may be related to breast carcinogenesis. These associations may vary by breast cancer type. Using the prospective cohort Shanghai Women's Health Study (1997-2008) including 718 Chinese breast cancer cases, the authors evaluated baseline dietary intake of these factors and breast cancer risk and whether the associations varied by menopausal status and estrogen receptor (ER) and progesterone receptor (PR) status. They estimated associations using hazard ratios and 95% confidence intervals from Cox proportional hazards regression models and stratified analyses by menopausal status and ER/PR status. Lowest quantile of intake was used as the comparison group. For postmenopausal women, dietary intakes of methionine and B vitamins were not associated with breast cancer risk. For premenopausal women, higher intake of folate was associated with decreased breast cancer risk (hazard ratio = 0.58, 95% confidence interval: 0.34, 0.99 for the highest vs. lowest quintile of intake). Only niacin intake was associated with ER+/PR+ breast cancer risk (hazard ratio = 1.62, 95% confidence interval: 1.07, 2.46; P for trend = 0.04 for the highest vs. lowest quartile of intake). Findings support the hypothesis that high folate intake may reduce breast cancer risk and that the association may vary by menopausal and ER/PR status.     

Association of vegetable, fruit, and grain intakes with colorectal cancer: the Multiethnic Cohort Study

BACKGROUND: It is uncertain whether or not vegetables, fruit, or grains protect against colorectal cancer. OBJECTIVE: In a large prospective study, we investigated the association of vegetable, fruit, and grain intakes with colorectal cancer risk. DESIGN: Between 1993 and 1996, 85 903 men and 105 108 women completed a quantitative food-frequency questionnaire that included approximately 180 foods and beverages in the Multiethnic Cohort Study. A diagnosis of colorectal cancer was made in 1138 men and 972 women after an average follow-up of 7.3 y. Cox proportional hazards models were used to calculate multivariate-adjusted relative risks and 95% CIs for colorectal cancer. RESULTS: In men, multivariate adjustment for energy intake, dietary, and nondietary variables resulted in relative risks in the highest quintile group of 0.74 (95% CI: 0.59, 0.93; P for trend = 0.02) for vegetables and fruit combined, 0.80 (95% CI: 0.64, 0.99; P for trend = 0.09) for fruit alone, and 0.85 (95% CI: 0.69, 1.05; P for trend = 0.05) for vegetables alone. When colon and rectal cases were separated among men, the inverse associations were stronger for colon than for rectal cancer. In women, none of the associations with vegetables, fruit, or vegetables and fruit combined were significant. Grain intake was not associated with colorectal cancer for either men or women. CONCLUSION: The intake of vegetables and fruit was inversely related to colorectal cancer risk among men but not among women. The association appears stronger for colon than for rectal cancer.     

Antioxidant vitamins in the diet: relationships with other personal characteristics in Finland.

STUDY OBJECTIVE--The study aimed to reveal associations between dietary antioxidant vitamins and other personal characteristics. DESIGN--Population based, cross sectional survey. SETTING--Twenty seven rural, industrial, and semiurban communities in six different regions of Finland. PARTICIPANTS--Subjects included 5304 men and 4750 women aged 15 years or older, who were interviewed about their dietary habits at the baseline study of the Finnish Mobile Clinic Health Examination Survey, 1967-72. MAIN RESULTS--Intakes of carotenoids and vitamins A, E, and C were estimated from dietary history interviews covering the subjects' food consumption in the preceding year. In older age groups intakes of all the vitamins studied were low. Occupation had a profound effect on dietary antioxidant vitamins: intakes were highest in white collar workers and lowest in farmers; those classified as service workers, industrial workers, or housewives came in between. Current smoking was inversely associated with dietary carotenoids and vitamin C, especially in men. The vitamin intakes of ex-smokers were equal to or even slightly higher than those of never smokers. Married men had higher intakes of carotenoids and vitamin C than men living alone. Body mass index was not an important determinant of the intake of antioxidant vitamins. CONCLUSIONS--The associations of dietary antioxidant vitamins with sociodemographic characteristics and smoking were strong enough to exert a confounding or modifying effect in studies on diet and diseases.     

Calcium and vitamin D intakes in relation to risk of distal colorectal adenoma in women

The authors examined intakes of calcium and vitamin D, and interaction with retinol, in relation to risk of adenoma of the distal colon or rectum among 48,115 US women who were free of colorectal cancer or polyps, completed a food frequency questionnaire in 1980, and underwent endoscopy by 2002. They documented 2,747 cases of adenoma (1,064 large, 1,531 small, 2,085 distal colon, and 779 rectal). Total calcium intake was weakly associated with distal colorectal adenoma risk (multivariable relative risk (RR) for extreme quintiles = 0.88, 95% confidence interval (CI): 0.74, 1.04; p(trend) = 0.06), particularly for large adenoma (RR = 0.73, 95% CI: 0.56, 0.96; p(trend) = 0.02). Total vitamin D intake was weakly associated with reduced risk of distal colorectal adenoma (RR = 0.79, 95% CI: 0.63, 0.99; p(trend) = 0.07), but more strongly with distal colon adenoma risk (RR = 0.67, 95% CI: 0.52, 0.87; p(trend) = 0.004). The combinations of high vitamin D and low retinol intake (RR = 0.55, 95% CI: 0.28, 1.10) further decreased risk of distal colorectal adenoma when compared with the opposite extreme. Higher total calcium and vitamin D intakes were associated with reduced risk, and the actions of vitamin D may be attenuated by high retinol intake.     

Dietary fat and fatty acids and risk of colorectal cancer in women

The authors examined the association of intakes of different types of fat and fatty acids with risk of colorectal cancer using data from the Women's Health Study, a randomized trial of low-dose aspirin and vitamin E carried out among 39,876 healthy US women aged >/=45 years. Among the 37,547 women eligible for the present study, 202 developed colorectal cancer during an average follow-up period of 8.7 years (1993-2003). Intakes of dietary fat and its food sources were assessed at baseline by food frequency questionnaire. Cox proportional hazards regression was used to estimate relative risks and 95% confidence intervals. Total fat intake was not related to colorectal cancer risk, nor were intakes of the different types of fat and major fatty acids. However, the authors observed a positive association between intake of fried foods away from home and colorectal cancer risk (highest quintile vs. lowest: relative risk = 1.86, 95% confidence interval: 1.09, 3.16; p for trend = 0.01). These prospective cohort data provide little support for an association between dietary fat and colorectal cancer risk. However, intake of fried foods and/or other factors related to their intake may be associated with colorectal cancer development. This finding warrants further examination.     

Vitamin A, retinol, and carotenoids and the risk of gastric cancer: a prospective cohort study

BACKGROUND: Vitamin A may influence gastric carcinogenesis through its essential role in controlling cell proliferation and differentiation. However, epidemiologic studies of vitamin A, retinol (preformed vitamin A), and provitamin A carotenoids in relation to the risk of gastric cancer have documented inconsistent results. OBJECTIVE: The objective of the study was to examine the associations between intakes of vitamin A, retinol, and specific carotenoids and the risk of gastric cancer in a prospective population-based cohort study of Swedish adults. DESIGN: The study cohort consisted of 82 002 Swedish adults aged 45-83 y who had completed a food-frequency questionnaire in 1997. The participants were followed through June 2005. RESULTS: During a mean 7.2-y follow-up, 139 incident cases of gastric cancer were diagnosed. High intakes of vitamin A and retinol from foods only (dietary intake) and from foods and supplements combined (total intake) and of dietary alpha-carotene and beta-carotene were associated with a lower risk of gastric cancer. The multivariate relative risks for the highest versus lowest quartiles of intake were 0.53 (95% CI: 0.32, 0.89; P for trend = 0.02) for total vitamin A, 0.56 (95% CI: 0.33, 0.95; P for trend = 0.05) for total retinol, 0.50 (95% CI: 0.30, 0.83; P for trend = 0.03) for alpha-carotene, and 0.55 (95% CI: 0.32, 0.94; P for trend = 0.07) for beta-carotene. No significant associations were found for beta-cryptoxanthin, lutein and zeaxanthin, or lycopene intake. CONCLUSION: High intakes of vitamin A, retinol, and provitamin A carotenoids may reduce the risk of gastric cancer.     

Prospective study of dietary supplements, macronutrients, micronutrients, and risk of bladder cancer in US men

Data derived from laboratory investigations suggest that a number of dietary variables may contribute to bladder carcinogenesis. Although bladder cancer is the fourth leading cause of cancer in men in the United States, dietary studies are few. The authors examined the relations between intakes of macro- and micronutrients and the risk of bladder cancer among men in the prospective Health Professionals Follow-Up Study. Each participant completed a 131-item food frequency questionnaire in 1986 and in 1990, from which nutrient intakes were calculated. During 12 years of follow-up, 320 cases of bladder cancer were diagnosed. No association was observed for total caloric or macronutrient intake and bladder cancer risk. Similarly, we found no relation for dietary intake of potassium, sodium, calcium, magnesium, phosphorus, iron, or water-soluble vitamins and bladder cancer risk. Total vitamin E intake and vitamin E supplements were inversely associated with risk. In addition, a dose-response relation was observed for duration of vitamin E supplement use. A suggestive inverse association was seen with dose of vitamin C supplement use. More studies are needed to determine the role of vitamins E and C supplement intake in bladder carcinogenesis.     

Dietary folate, vitamin B6, vitamin B12 and methionine intake and the risk of breast cancer by oestrogen and progesterone receptor status

Few studies have evaluated the relationship between the consumption of dietary folate and one-carbon metabolism-related nutrients and breast cancer risk defined by oestrogen receptor (ER) and progesterone receptor (PR) status. The objective of the present study was to examine the associations between dietary folate, vitamin B6, vitamin B12, and methionine intake and the risk of breast cancer by ER and PR status among Chinese women in Guangdong. A hospital-based case-control study was conducted from June 2007 to August 2008, with 438 cases and 438 age (5-year interval)- and residence (rural/urban)-matched controls. Dietary intake information was assessed using a validated FFQ administered through a face-to-face interview. Unconditional logistic regression models were used to calculate multivariate-adjusted OR and 95 % CI. A significant inverse association was found between dietary folate and vitamin B6 intake and breast cancer risk. The adjusted OR of the highest v. the lowest quartile were 0·32 (95 % CI 0·21, 0·49; P(trend) < 0·001) for dietary folate and 0·46 (95 % CI 0·30, 0·69; P(trend) < 0·001) for vitamin B6. No associations were observed for vitamin B12 and methionine intake. A significant inverse association between dietary folate intake and breast cancer risk was observed in all subtypes of ER and PR status. These findings suggest that dietary folate and vitamin B6 intakes were inversely associated with breast cancer risk. The inverse association did not differ by ER and/or PR status.     

Intakes of Vitamin A,C, and E,and β-Carotene Are Associated With Risk of Cervical Cancer: A Case-Control Study in Korea

Cervical cancer is one of the most common gynecological malignancies in Korea, although the incidence has been declining in recent years. This study explored whether antioxidant vitamin intakes influenced the risk of cervical cancer. The association between antioxidant vitamin intakes and cervical cancer risk was calculated for 144 cervical cancer cases and 288 age-matched, hospital-based controls using unconditional logistic regression models. Cases reported statistically lower mean dietary intakes of vitamin A, β -carotene, and vitamin C than did controls. Total intakes of vitamins A and E, which included both dietary and supplement intake, were also lower in cases. Those patients in the highest quartiles of dietary vitamin A, β -carotene, and vitamin C intakes had statistically significantly lower cervical cancer risks than those in the lowest quartiles for vitamin A, β -carotene, and vitamin C: odds ratio (OR) = 0.36 [95% confidence interval (CI) = 0.19–0.69), OR = 0.48 (CI = 0.26–0.88), and OR = 0.36 (CI = 0.18–0.69), respectively. Total intakes of vitamins A, C, and E were strongly inversely associated with cervical cancer risk: OR = 0.35 (CI = 0.19–0.65), OR = 0.35 (CI = 0.19–0.66), and OR = 0.53 (CI = 0.28–0.99), respectively. The findings support a role for increased antioxidant vitamin intake in decreasing the risk of cervical cancer. These associations need to be assessed in large prospective studies with long-term follow-up.     

Flavonoid intake and colorectal cancer risk in men and women

Dietary flavonoids can inhibit cancer development by protecting tissues against free oxygen radicals and inhibiting cell proliferation, but observational studies of flavonoid intake and colorectal cancer incidence are sparse. The authors prospectively evaluated the association between intake of flavonoids and colorectal cancer incidence in 71,976 women from the Nurses' Health Study and 35,425 men from the Health Professionals Follow-Up Study. Dietary intake was assessed in 1990, 1994, and 1998 by means of a food frequency questionnaire. The authors used Cox proportional hazards models with time-varying variables to estimate relative risks of colorectal cancer. Between 1990 and 2000, the authors documented 878 incident cases of colorectal cancer (498 in women and 380 in men). Total flavonoid intake was not inversely associated with colorectal cancer risk among women and men combined. The combined relative risk for the highest quintile of total flavonoid intake compared with the lowest was 1.19 (95% confidence interval: 0.94, 1.49; p for trend = 0.15). Higher intakes of individual flavonols, including quercetin, myricetin, and kaempferol, were also not related to a lower risk of colorectal cancer. These data provide little support for the hypothesis of an association between flavonoid intake and colorectal cancer risk, at least within the ranges of intakes consumed in the populations studied.     

Relationship of folate,vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers

It is hypothesized that diets deficient in folate, methionine, and vitamins B-6 and B-12 cause DNA hypomethylation and, as a result, increase risk of colorectal cancers. Furthermore, it is proposed that alcohol, a methyl group antagonist, increases risk of colorectal cancers among those with low intake of folate. Data from the Iowa Women's Health Study, a population-based cohort of incident cancer, were used to examine the relationship of folate, methionine, and vitamins B-6 and B-12 to occurrence of cancers of the colon (n = 598) and rectum (n = 123) over 13 yr of follow-up. There were no independent associations of folate, methionine, or vitamins B-6 and B-12 derived from a food frequency questionnaire with incidence of colon cancer. Adjusted relative risks (RRs) of rectal cancer were similar across categories of folate, vitamin B-12, and methionine intake, but RRs increased progressively with increasing intake of vitamin B-6 [P (for trend) = 0.03]. RRs suggested that incidence of cancer of the proximal colon was lower among those with 1) high folate and high vitamin B-12 intake [RR = 0.59, 95% confidence interval (CI) = 0.39-0.89] and 2) high folate and high vitamin B-6 intake (RR = 0.65, 95% CI = 0.50-0.84) than among those with the lowest intake of these nutrients. Incidence of cancer of the proximal colon was also somewhat lower among those with high folate and low alcohol intake (RR = 0.44, 95% CI = 0.22-0.89). Findings provide limited support for an association between dietary factors involved in DNA methylation and risk of cancers of the colon and rectum.