A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

We examined the relationship between a functional polymorphism (C-667-->T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [ relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas, This lack of association wa s observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.3 2, 95% CI 0.66-2.66) adenomas, Furthermore, there was no significant intera ction between this polymorphism and consumption of either folate, methionin e or alcohol. We also examined the relationship of a newly identified polym orphism (asp919gly) of the methionine synthase gene (MS) with the risk of c olorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0. 66, 95% CI 0.26-1.70). These results, which need to be confirmed in other s tudies, suggest that the MTHFR val/val polymorphism, which has been previou sly inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-->carcinoma) of colorectal tumorigenesis, and/or m ay protect against malignant transformation in the subset of benign adenoma s, which may progress to malignancy.