Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk.

SCOPE: We reevaluated previously reported associations between variants in pathways of one-carbon (1-C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake. METHODS AND RESULTS: Odds ratios (OR) for 446 genetic variants were estimated among 13,410 OC cases and 22,635 controls, and among 2281 cases and 3444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for dihydropyrimidine dehydrogenase (DPYD) variants rs11587873 (OR = 0.92; p = 6 × 10⁻5) and rs828054 (OR = 1.06; p = 1 × 10⁻4). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with folate in a multivariant analysis (corrected p = 9.9 × 10⁻6) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in 1-C transfer, previously reported with OC, suggested lower risk at higher folate (p(interaction) = 0.03-0.006). CONCLUSION: Variation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP-by-folate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC.

Antioxidant vitamins intake and the risk of coronary heart disease: meta-analysis of cohort studies.

BACKGROUND: Many epidemiological studies have reported that antioxidant vitamin intake from diet or supplements are associated with a lower risk of coronary heart disease (CHD), the findings are, however, inconsistent. We undertook a meta-analysis of cohort studies to examine the relations between antioxidant vitamins (vitamins C, E, and beta-carotene) and CHD risk. METHODS AND RESULTS: We included all the relevant cohort studies if they provided a relative risk and corresponding 95% confidence interval (CI) of CHD in relation to antioxidant vitamins intake from diet or supplement. Fifteen cohort studies were identified involving a total of 7415 incident CHD cases and 374,488 participants with a median follow-up of approximately 10, 8.5, and 15 years for vitamins C, E, and beta-carotene, respectively. Pooled estimates across studies were obtained by random-effects model. The potential sources of heterogeneity and publication bias were also estimated. For vitamins C, E, and beta-carotene, a comparison of individuals in the top third with those in the bottom third of baseline value yielded a combined relative risk of 0.84 (95% CI, 0.73-0.95), 0.76 (95% CI, 0.63-0.89), and 0.78 (95% CI, 0.53-1.04), respectively. Subgroup analyses show that dietary intake of vitamins C and E and supplement use of vitamin E have an inverse association with CHD risk, but supplement use of vitamin C has no significant association with CHD risk. In the dose-response meta-analysis, each 30 mg/day increase in vitamin C, 30 IU/day increase in vitamin E, and 1 mg/day increase in beta-carotene yielded the estimated overall relative risk for CHD of 1.01 (95% CI, 0.99-1.02), 0.96 (95% CI, 0.94-0.99), and 1.00 (95% CI, 0.88-1.14), respectively. CONCLUSIONS: Our findings in this meta-analysis suggest that an increase in dietary intake of antioxidant vitamins has encouraging prospects for possible CHD prevention.