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.     

Dietary Intake of B Vitamins and Methionine and Colorectal Cancer Risk

B vitamins are involved in 1-carbon metabolism, which is necessary for DNA replication, DNA repair, and regulation of gene expression. Recent studies suggest inverse associations between folate and vitamin B6 intakes and colorectal cancer risk but associations with other B vitamins and methionine have not been widely studied. After following 14,645 men and 22,467 women for 15 yr on average, we ascertained 910 incident colorectal cancers. Dietary intakes were estimated using a 121-item food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals were estimated using Cox regression. We found some evidence of a U-shaped relationship between colon cancer risk and vitamin B6 and an inverse U-shaped relationship between rectal cancer risk and B12 (test for the quadratic trend, P = 0.005 and P = 0.0005 respectively). For colon cancer, we observed a reduced risk associated with low methionine/high folate, HR = 0.63 (0.49, 0.80) and an increased risk associated with high methionine/high folate, HR = 1.36 (1.06, 1.74) (P interaction < 0.0001). Our study suggests a U-shaped association between colon cancer risk and vitamin B6 intake and an inverse U-shaped association between rectal cancer risk and vitamin B12. Adequate folate intake might protect against colon cancer risk in those with low methionine intake.     

Intake of folate and related nutrients in relation to risk of epithelial ovarian cancer

Assessments of the relation between folate intake and ovarian cancer risk have been limited and inconsistent. Therefore, the authors prospectively examined the association of dietary and supplemental intakes of folate, methionine, and vitamin B(6) with ovarian cancer risk among 80,254 Nurses' Health Study participants. Beginning in 1976, women completed biennial questionnaires assessing ovarian cancer risk factors; starting in 1980, food frequency questionnaires were administered every 2-4 years. During 22 years of follow-up (1980-2002), the authors confirmed 481 incident epithelial ovarian cancers. There were no associations between total folate (top quintile vs. bottom: relative risk (RR) = 1.21, 95% confidence interval (CI): 0.92, 1.60), methionine (RR = 1.00, 95% CI: 0.76, 1.33), dietary vitamin B(6) (RR = 1.09, 95% CI: 0.81, 1.47), or total vitamin B(6) (RR = 1.13, 95% CI: 0.85, 1.51) intake and ovarian cancer risk. Higher dietary folate was associated with a modestly decreased risk after exclusion of cases diagnosed during the 4 follow-up years after dietary assessment (RR = 0.66, 95% CI: 0.43, 1.03) and for the serous subtype (RR = 0.51, 95% CI: 0.31, 0.84). Results did not vary by alcohol intake, multivitamin use, menopausal status, or oral contraceptive use. There was little evidence that folate, methionine, and vitamin B(6) are important in ovarian cancer risk, although dietary folate was inversely associated with risk in some analyses.     

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.     

Folate and alcohol intakes: Related or independent roles in the adenoma‐carcinoma sequence?

Epidemiologic studies have suggested that high alcohol and low folate intakes might be jointly associated with colorectal tumors via DNA metabolism. We investigated this hypothesis in a case‐control study comparing small adenoma (<10 mm, n = 154), large adenoma (n = 208), and polyp‐free (n = 426) subjects, recruited after colonoscopy, and cancer cases (n = 171) with population controls (n = 309). Odds ratios for the fifth vs. the first quintile of intake (OR₅) were as follows: Folate intake was related to the risk of small and large adenomas compared with polyp‐free subjects [OR₅ = 0.5, 95% confidence interval (CI) 0.3–1.0; OR₅ = 0.5, 95% CI 0.3–1.0, respectively], whereas alcohol was related to risk of large adenomas (OR₅ = 4.1, 95% CI 2.1–8.1), but not of small adenomas (OR₅ = 1.2, 95% CI 0.7–2.2). In large adenomas, there was some interaction between alcohol and folate, with a stronger protective effect of folate with high alcohol intake and a stronger risk with alcohol in subjects with low folate intake. For cancer patients compared with general population controls, neither alcohol (OR₅ = 1.6, 95% CI 0.8–3.0) nor folates (OR₅ = 1.0, 95% CI 0.5–2.0) were related to risk. Our data support the hypothesis that folate intake might be mostly beneficial to prevent adenoma formation but might have an additional protective effect against adenoma growth associated with alcohol.     

Case-control analysis of dietary folate and risk of bladder cancer

Dietary folate, a water-soluble B vitamin found in a variety of fruits and vegetables, is of particular interest as a chemopreventive agent due to its role in DNA methylation and DNA synthesis and repair. We hypothesized that individuals with low folate intake would be at an increased risk for bladder cancer. Using an ongoing case-control study we assessed dietary folate in 409 incident bladder cancer patients and 451 healthy control subjects. A food-frequency questionnaire was used to estimate naturally occurring food folate (microg/kcal/day), dietary folate equivalents (DFE) from food sources (microg DFE/kcal/day), and DFE from all sources (microg DFE/kcal/day). Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Bladder cancer patients reported a statistically significant lower intake of folate than control subjects for food folate and DFE from food sources (P < 0.001) but not for DFE from all sources (P = 0.061). In the highest quartile of food folate intake there was a 54% reduced risk for bladder cancer (OR = 0.46; 95% CI = 0.29-0.73) after adjusting for age, gender, ethnicity, smoking, and total energy intake. Similarly, the highest quartile of intake was associated with a 59% reduced risk for DFE from food sources (OR = 0.41; 95% CI = 0.26-0.65) and a 35% reduced risk for DFE from all sources (OR = 0.65; 95% CI = 0.42-1.00). In the joint-effects analyses using never smokers with high folate intake as the reference group (OR = 1.0), heavy smokers with low food folate intake had a 2.31-fold (95% CI = 1.11-4.82) increased risk, whereas heavy smokers with high folate intake had a reduced OR of 1.31 (95% CI = 0.53-3.26). Although the ORs were not statistically significant, light smokers and high folate intake exhibited a protective effect (OR = 0.62; 95% CI = 0.20-1.94), whereas an increased risk was observed for light smoking and low folate intake (OR = 1.41; 95% CI = 0.57-3.45). These patterns were consistent for the joint effects of smoking and DFE from food sources and DFE from all sources. In summary, high intake of dietary folate was associated with an overall decrease in bladder cancer risk. These data may have important implications for cancer prevention; however, large, hypothesis-driven, population-based clinical trials will be required to confirm these findings.     

Folate intake, serum homocysteine and methylenetetrahydrofolate reductase (MTHFR) C677T genotype are not associated with oral cancer risk in Puerto Rico

We examined the relationships between folate and methionine intake, serum homocysteine levels (as a biomarker for folate metabolism), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism genotype and risk of oral cancer in a population-based, case-control study in Puerto Rico. Structured questionnaires were used to collect information on demographic factors, usual adult diet, and tobacco and alcohol use. Oral epithelial cells and blood samples were collected from a subset of subjects. Analyses were conducted by logistic regression, adjusting for age, sex, lifetime smoking and lifetime alcohol intake, with the following numbers of cases/controls, respectively: dietary data (341/521); MTHFR genotype (148/149); and homocysteine (60/90). Although increased folate intake was associated with decreased oral cancer risk [adjusted odds ratio (OR) in highest vs. lowest quartile = 0.6, 95% confidence interval (CI): 0.4, 1.0, P(trend) = 0.05)], this finding was due almost entirely to folate intake from fruit (adjusted OR = 0.4, 95% CI: 0.2, 0.6; P(trend) = 0.0001), whereas other dietary folate sources showed no clear association. Methionine intake and serum homocysteine levels were not associated with oral cancer risk. Subjects with the MTHFR C677T homozygous variant (TT) genotype had a nonsignificantly lower risk, and risk patterns tended to differ by level of folate, methionine, alcohol intake and smoking, although the power to detect significant associations in subgroups of these variables was low. Risks for oral cancer are not folate specific; preventive recommendations for this disease should emphasize the importance of a healthy diet, including substantial intake of fruits.     

Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of folate and related B vitamins and colorectal cancer: a case-control study in a population with relatively low folate intake

Folate is key in one-carbon metabolism, disruption of which can interfere with DNA synthesis, repair, and methylation. Efficient one-carbon metabolism requires other B vitamins and the optimal activity of enzymes including 5,10-methylenetetrahydrofolate reductase (MTHFR). We report a population-based case-control study of folate intake, related dietary factors and MTHFR polymorphisms (C677T, A1298C) and colorectal cancer in a population with relatively high colorectal cancer incidence and relatively low folate intake. A total of 264 cases with histologically confirmed incident colorectal cancer and 408 controls participated. There was no clear trend in risk with reported intakes of total, or dietary, folate, riboflavin, vitamin B12 or vitamin B6, nor were there interactions between folate intake and the other B vitamins or alcohol. For C677T, risk decreased with increasing variant alleles (multivariate OR for CT v. CC = 0.77 (95 % CI 0.52, 1.16); OR for TT v. CC = 0.62 (95 % CI 0.31, 1.24)), which, although not statistically significant, was consistent with previous studies. For A1298C, compared with AA subjects, CC subjects had modest, non-significant, reduced risk (multivariate OR = 0.81 (95 % CI 0.45, 1.49)). There were significant interactions between total folate and C677T (P = 0.029) and A1298C (P = 0.025), and total vitamin B6 and both polymorphisms (C677T, P = 0.016; A1298C, P = 0.033), although the patterns observed differed from previous studies. Seen against the setting of low folate intake, the results suggest that the role of folate metabolism in colorectal cancer aetiology may be more complex than previously thought. Investigation of particular folate vitamers (for example, tetrahydrofolate, 5,10-methylenetetrahydrofolate) may help clarify carcinogenesis pathways.     

Associations Between Intake of Folate and Related Micronutrients with Molecularly Defined Colorectal Cancer Risks in the Iowa Women's Health Study

Folate and related micronturients may affect colorectal cancer (CRC) risk, but the molecular mechanism(s) remain incompletely defined. We analyzed associations between dietary folate, vitamin B6, vitamin B12, and methionine with incident CRC, overall and by microsatellite instability (MSS/MSI-L or MSI-H), CpG island methylator phenotype (CIMP-negative or CIMP-positive), BRAF mutation (negative or positive), and KRAS mutation (negative or positive) status in the prospective, population-based Iowa Women's Health Study (IWHS; 55–69 years at baseline; n = 41,836). Intake estimates were obtained from baseline, self-reported food frequency questionnaires. Molecular marker data were obtained for 514 incident CRC cases. Folate intake was inversely associated with overall CRC risk in age-adjusted Cox regression models, whereas methionine intake was inversely associated with overall CRC risk in multivariable-adjusted models [relative risk (RR) = 0.81; 95% CI = 0.69–0.95; P trend = 0.001 and RR = 0.72; 95% CI = 0.54–0.96; P trend = 0.03 for highest vs. lowest quartiles, respectively]. None of the dietary exposures were associated with MSI, CIMP, BRAF, or KRAS defined CRC subtypes. These data provide minimal support for major effects from the examined micronutrients on overall or molecularly defined CRC risks in the IWHS cohort.     

Dietary factors of one-carbon metabolism and prostate cancer risk

BACKGROUND: Folate is hypothesized to be inversely associated with the risk of several cancers, but such a potential association has not been well studied for prostate cancer. Vitamin B-6, vitamin B-12, methionine, and alcohol can influence folate-related metabolism. OBJECTIVE: The objective was to investigate the associations between dietary factors of one-carbon metabolism and prostate cancer risk within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study. DESIGN: Of the cohort's 27 111 Finnish male smokers aged 50-69 y who had complete dietary data, 1270 had a diagnosis of incident prostate cancer between 1985 and 2002. Folate, vitamin B-6, vitamin B-12, methionine, and alcohol intakes were estimated from a 276-item modified dietary history questionnaire. Cox proportional hazard models, adjusted for age and vitamin supplement use, estimated relative risks (RR) and 95% CIs. RESULTS: Vitamin B-6 intake was inversely associated with prostate cancer risk (RR for highest versus lowest quintile: 0.88; 95% CI: 0.72, 1.07; P for trend = 0.045), whereas vitamin B-12 intake was associated with significantly increased risk (RR = 1.36; 95% CI: 1.14, 1.96; P for trend = 0.01). No association between folate or alcohol intake and prostate cancer risk was observed. No differences were found in the above associations according to stage of disease or subgroups of several potential effect modifiers. CONCLUSIONS: We found no convincing evidence for a protective role of one-carbon metabolism against prostate cancer, although these observations can be generalized only to smokers. The possible modest protective association with vitamin B-6 and the significantly elevated risk with vitamin B-12 intake warrant further investigation.     

Dietary folate and APC mutations in sporadic colorectal cancer

Folate deficiency has been associated with colorectal cancer risk and may be involved in colorectal carcinogenesis through increased chromosome instability, gene mutations, and aberrant DNA methylation. Within the Netherlands Cohort Study on diet and cancer, we investigated the associations between dietary folate intake and colorectal cancer risk with (APC(+)) and without (APC(-)) truncating APC mutations, accounting for hMLH1 expression and K-ras mutations. In total, 528 cases and 4200 subcohort members were available for data analyses of the study cohort (n = 120,852) from a follow-up period between 2.3 and 7.3 y after baseline. Adjusted gender-specific incidence rate ratios (RR) over tertiles of folate intake were calculated in case-cohort analyses for colon and rectal cancer. Although relatively high folate intake was not associated with overall colorectal cancer risk, it reduced the risk of APC(-)colon tumors in men (RR 0.58, 95% CI 0.32-1.05, P(trend) = 0.06 for the highest vs. lowest tertile of folate intake). In contrast, it was positively associated with APC(+) colon tumors in men (highest vs. lowest tertile: RR 2.77, 95% CI 1.29-5.95, P(trend) = 0.008) and was even stronger when the lack of hMLH1 expression and K-ras mutations were excluded (RR 3.99, 95% CI 1.43-11.14, P(trend) = 0.007). Such positive associations were not observed among women; nor was folate intake associated with rectal cancer when APC mutation status was taken into account. Relatively high folate consumption reduced the risk of APC(-) colon tumors, but folate intake was positively associated with APC(+) colon tumors among men. These opposite results may indicate that folate enhances colorectal carcinogenesis through a distinct APC mutated pathway.     

Dietary Intakes of Selected Nutrients and Food Groups and Risk of Cervical Cancer

We investigated the relationships between intakes of selected dietary nutrients and food groups and risk of cervical cancer in a hospital-based, case-control study including 239 cases diagnosed with squamous cell carcinoma of the cervix and 979 hospital patients with nonneoplastic diagnoses who completed a self-administered questionnaire between 1982 and 1998 at Roswell Park Cancer Institute. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression adjusting for age, education, smoking status, use of oral contraceptives, barrier contraceptives and spermicides, family history of cervical cancer, year questionnaire completed, and energy intake. Significant reductions in risk of approximately 40–60% were observed for women in the highest vs. lowest tertiles of dietary fiber (OR = 0.59, 95% CI = 0.37–0.94), vitamin C (OR = 0.52, 95% CI = 0.33–0.80), vitamin E (OR = 0.44, 95% CI = 0.27–0.72), vitamin A (OR = 0.47, 95% CI = 0.30–0.73), α -carotene (OR = 0.41, 95% CI = 0.27–0.63), β -carotene (OR = 0.44, 95% CI = 0.29–0.68), lutein (OR = 0.51, 95% CI = 0.33–0.79), folate (OR = 0.55, 95% CI = 0.34–0.88), and total fruit and vegetable intake (OR = 0.52, 95% CI = 0.34–0.77). Our findings suggest that a diet rich in plant-based nutrients may be important in reducing the risk of cervical cancer.     

Effect of nutrient intake and Helicobacter pylori infection on gastric cancer in Korea: a case-control study

To examine the effects of dietary factor and Helicobacter pylori (H. pylori) infection with emphasis on vitamin intake on the risk of gastric cancer (GC), we conducted a case-control study in South Korea, a high-risk area for GC. Trained dietitians interviewed 136 cases histologically diagnosed with GC. An equal number of hospital controls was selected by matching sex and age. High dietary intakes of vegetable fat [odds ratio (OR) = 0.35; 95% confidence interval (CI) = 0.15-0.83], folate (OR = 0.35; 95% CI = 0.13-0.96), and antioxidants, such as vitamin A (OR = 0.34; 95% CI = 0.13-0.83), beta-carotene (OR = 0.33; 95% CI = 0.13-0.82), vitamin C (OR = 0.26; 95% CI = 0.09-0.72), and vitamin E (OR = 0.41; 95% CI = 0.17-1.01), were shown to have a protective effect on GC risk using a multivariate model adjusting for foods significantly related to GC in our previous study (charcoal grilled beef, spinach, garlic, mushroom, and a number of types of kimchi) and supplement use. When stratified according to H. pylori infection, high intakes of vitamin C (OR = 0.10; 95% CI = 0.02-0.63) and vitamin E (OR = 0.16; 95% CI = 0.03-0.83) exhibited highly significant inverse associations with GC among the H. pylori-infected subjects compared with noninfected individuals. GC risk was significantly decreased only when consumption levels for two of these vitamins were high. Our findings suggest that high intake of antioxidant vitamins contribute to the reduction of GC risk and that GC risk in Korea may be decreased by encouraging those with H. pylori infection to increase their intake of antioxidant vitamins.     

Thirty Years Ago…

Nitrate is a precursor in the endogenous formation of N-nitroso compounds, which are potent animal carcinogens, whereas antioxidant vitamins have been suggested to protect against carcinogenesis. Interestingly, nitrate and antioxidant vitamins stem from the same dietary sources. We investigated whether the intake of nitrate relative to antioxidant vitamins is associated with the risk of breast cancer. A total of 362 breast cancer cases were matched to the 362 controls by age and menopausal status. Dietary intake was assessed using a quantitative food frequency questionnaire with 121 food items by trained interviewers. The nitrate to antioxidant vitamin consumption ratio was then calculated. Conditional logistic regression analysis was used to obtain odds ratios (ORs) and corresponding 95% confidence intervals (CI). Mean intakes of nitrate for cases and controls were 421 mg/day and 424 mg/day, respectively. Intakes of nitrate, nitrate/β-carotene, nitrate/vitamin C, and nitrate/vitamin E were not associated with breast cancer risk. However, higher breast cancer risk was observed with higher intake of nitrate/folate (OR = 2.03, 95% CI = 1.16–3.54, P for trend = 0.052). Our results suggest that lowering the ratio of nitrate to folate intake may be effective in reducing breast cancer risk.     

A Case-Control Nutrigenomic Study on the Synergistic Activity of Folate and Vitamin B12 in Cervical Cancer Progression

The present study was designed to identify the role of folate, B12, homocysteine, and polymorphisms of methylene tetrahydrofolatereductase (MTHFR) gene in cervical carcinogenesis among 322 women from Kerala, South India. Serum folate, vitamin B12 (chemiluminescence assay), and homocysteine (EIA) along with genetic polymorphisms of MTHFR gene (polymerase chain reaction/restriction fragment length polymorphism) were analyzed for 136 control subjects, 92 low-grade squamous intraepithelial lesions (LSIL) subjects, and 94 invasive cervical cancer cases (ICC). Statistically significant associations between MTHFR polymorphisms, serum homocysteine, and folate levels with cervical carcinogenesis were not evident, but we found that these parameters acted as effect modifiers of serum vitamin B12. The risk estimates observed for B12 became prominent only when there was a deficiency in serum folate levels [LSIL–odds ratio (OR): 14.9 (95% CI: 2.65 to 84.4); ICC–OR = 8.72 (95% CI = 1.55 to 48.8)] or when MTHFR A1298C polymorphic variant was present [LSIL–OR = 9.8 (95% CI = 2.61 to 36.7); ICC–OR = 10.0 (95%CI = 2.5 to 39.3)]. The statistical significance of this effect modification was further studied using an interaction model, where only folate was observed to have an influence on B12 levels as suggested by the odds ratio of 7.11 (95% CI = 0.45 to 111.9) obtained for ICC group, implicating a synergistic role of these 2 vitamins in invasive cervical cancer.     

Alcohol and Dietary Folate Intake and Promoter CpG Island Methylation in Clear-Cell Renal Cell Cancer

We investigated whether alcohol and dietary folate intakes were associated with promoter methylation in clear-cell renal cell carcinoma (ccRCC). The Netherlands Cohort Study with a case-cohort design included 120,852 subjects aged 55–69 yr in 1986. Diet was measured with a food-frequency questionnaire. After 20.3 yr of follow-up, paraffin-embedded tumor blocks were collected. Methylation-specific polymerase chain reaction (MSP) was used to analyze promoter methylation of 11 genes. ccRCC cases were classified into low (0–19% of the genes), intermediate (20–39%), and high (40%+) methylation. Multivariable Cox regression analyses were conducted, stratified according to methylation, including 3980 subcohort members and 297 ccRCC cases. Increasing alcohol intake was associated with decreased ccRCC risk, but was not statistically significant; multivariable adjusted hazard ratio (HR) for ≥30 g alcohol/day versus 0 g/day was 0.78 [95% confidence interval (CI): 0.48–1.24], and P-value for trend was 0.46. In strata according to methylation index, no significant heterogeneity was observed. Dietary folate intake was not associated with ccRCC risk. There was no significant heterogeneity between strata according to methylation index. There was no effect modification of alcohol and dietary folate intake on ccRCC risk, nor in strata according to methylation index. Our findings do not support the hypothesis that alcohol and dietary folate intakes are involved in ccRCC.     

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.     

Calcium,Vitamin D,VDR Genotypes,and Epigenetic and Genetic Changes in Rectal Tumors

Calcium, vitamin D, exposure to sunshine, and vitamin D receptor (VDR) genotypes have been associated rectal cancer. We used data from 750 rectal tumors and 1,205 population-based controls examine associations with TP53, KRAS2, and CpG Island methylator phenotype (CIMP) markers. Rectal tumors were associated with high levels of calcium overall and with TP53 tumor mutations specifically (OR = 0.6, 95% CI = 0.42–0.84). High levels of sunshine exposure had a borderline protective effect for TP53 tumor mutations (OR = 0.78, 95% CI = 0.59–1.03). A mutation at codon 248 was significantly associated with dietary calcium intake (OR = 0.26, 95% CI = 0.09–0.77); having the Ff/ff genotypes of the FOK1 VDR polymorphism significantly increased the odds of a mutation at codon 245 (OR = 4.74, 95% CI = 1.05–21.39); high levels of dietary vitamin D (OR = 3.42, 95% CI = 1.15–10.17) and the Ff/ff genotypes of FOK1 (OR = 3.34, 95% CI = 1.11–10.02) and the GA/AA genotypes of the CDX2 VDR polymorphism (OR = 2.85, 95% CI = 1.23–6.58) increased the odds of a TP53 mutation at codon 273. These data support an association between calcium and rectal tumors overall as well as specifically with TP53 mutations. However, given the number of comparisons, findings need to be confirmed in other studies.     

Folate and vitamin B(6) intake and risk of acute myocardial infarction in Italy

BACKGROUND: Folate and vitamin B6 intake has been associated with reduced risk of coronary heart disease, but studies are not consistent. OBJECTIVE: The relation between folate and vitamin B6 intake and the risk of acute myocardial infarction (AMI) was assessed in a Mediterranean population. DESIGN: A hospital-based case-control study was conducted in Milan, Italy, between 1995 and 1999. Information was collected by interviewer-administered questionnaires. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) were obtained by multiple logistic regression models. SUBJECTS: Cases were 507 patients with a first episode of nonfatal AMI, and controls were 478 patients admitted to hospital for acute conditions. RESULTS: Compared to patients in the lowest tertile of intake, the ORs for those in the highest tertile were 0.56 (95% CI 0.35-0.88) for folate and 0.34 (95% CI 0.19-0.60) for vitamin B6. The OR was consistently below unity in strata of sex, age, alcohol, methionine, tobacco smoking, coffee, hypertension and family history of AMI; the inverse association was apparently stronger for vitamin B6 in regular alcohol drinkers than in no or occasional drinkers. Compared to subjects with a low intake of both micronutrients, the OR was 0.29 for those with a high intake of both. Compared to subjects reporting no or occasional alcohol drinking and low methionine and folate intake, the OR was 0.28 in regular drinkers with high methionine and high folate intake. The corresponding value for vitamin B6 was 0.25. CONCLUSIONS: A high intake of folates, vitamin B6 and their combination is inversely associated with AMI risk. SPONSORSHIP: Partly supported by "Ministero della Salute" (Contract No. 177, RF 2001).