Association of dietary and supplemental folate intake and polymorphisms of the MTHFR, MTHFD1, and TYMS genes and colorectal cancer in a population‐based study

Abstract

We evaluated the role of dietary and supplemental folate and 40 polymorphisms from three genes involved in folate‐mediated one‐carbon metabolism (FOCM) on colorectal cancer (CRC) risk in a population‐based case‐control study in Pennsylvania. Cases and controls reported dietary intakes and supplement use for the year before diagnosis or interview, respectively, via a modified food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression to assess the effect of folate from the diet and supplements and from FOCM genes (MTHFR, MTHFD1, and TYMS) on CRC risk among 686 incident cases and 740 controls. After multivariate adjustment, CRC risk was not significantly associated with dietary or supplemental folate intake. However, compared to no use, folate supplement use was inversely associated with colon cancer risk (OR = 0.77; 95% CI = 0.59–1.00). In preliminary analysis, only the rs17824591 MTHFD1 polymorphism was significantly associated with CRC risk (OR per allele = 1.21, 95% CI = 1.01–1.45). Further investigation of gene‐environment interactions is needed to elucidate the impact of diet and FOCM‐related genes on CRC risk. Partial support by the Pennsylvania Department of Health – Grant #4100038714.Grant Funding Source: Pennsylvania Department of Health