Nutrients in Folate-Mediated, One-Carbon Metabolism and the Risk of Rectal Tumors in Men and Women

摘要

In an investigation of rectal tumors characterized by CpG is-nland methylator phenotype (CIMP), KRAS2 mutation, and TP53nmutation,we examined associationswith dietary and supplementalnfolate, riboflavin, vitamins B6 and B12, and methionine, nutrientsninvolved in folate-mediated 1-carbon metabolism. We also exam-nined folate intake and commonMTHFR polymorphisms in relationntoCIMP.Data froma population-based study of 951 cases (750withntumor markers) and 1,205 controls were evaluated using multiplenlogistic regression models and generalized estimating equations.nReduced risk of methylated tumors was suggested in women withnthe upper tertile of folate intake (≥0.42 mg/day) vs. the lower ter-ntile: OR = 0.6, 95%CI = 0.3–1.2. In men, a significant 3-fold in-ncreased risk of CIMP+ tumor was observed for the upper tertile ofnfolate (≥0.75 mg/day) vs. the lower tertile (<0.44 mg/day): OR =n3.2, 95%CI=1.5–6.7. Thesemen consumed a greater proportion ofnfolic acid fortified foods relative to natural, primarily plant-basednsources (52%vs. 48%) than women with CIMP+ tumors (22%vs.n78%). MTHFR 1298A>C influenced folate in male CIMP+ riskn(P interaction < 0.01). Our findings suggest folate supplementa-ntion effects may differ between genders, perhaps due to variation in MTHFR and/or endogenous/exogenous hormones, and may benimportant in the initiation and progression of methylated rectalntumors in men.