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

We examined the relationship between a functional polymorphism (667C-->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 MTHFRval/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 was observed for both small (RR = 1.36, 95% CI0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore,there was no significant interaction between this polymorphism andconsumption of either folate, methionine or alcohol. We also examined therelationship of a newly identified polymorphism (asp919gly) of themethionine synthase gene (MS) with the risk of colorectal adenomas in thesame population. The MS gly/gly polymorphism was also not significantlyassociated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70).These results, which need to be confirmed in other studies, suggest thatthe MTHFR val/val polymorphism, which has been previously inverselyassociated with risk of colorectal cancer, plays a role only in a latestage (adenoma-- >carcinoma) of colorectal tumorigenesis, and/or mayprotect against malignant transformation in the subset of benign adenomas,which may progress to malignancy.