Lack of association between the C677T MTHFR polymorphism and colorectal hyperplastic polyps

Colorectal hyperplastic polyps are benign lesions that share many risk fact ors with colorectal adenomas and cancers. Low folate intakes are associated with an increased risk of colon cancer. The enzyme 5,10-methylene-tetrahyd rofolate reductase (MTHFR) may be linked to DNA methylation and nucleotide synthesis and thus play a role in the etiology of colorectal neoplasia, we investigated an association between the common MTHFR polymorphism (C677T) a nd colorectal hyperplastic polyps within the Minnesota Cancer Prevention Re search Unit case-control study. Cases (n = 200) were diagnosed with colonos copically confirmed hyperplastic polyps; controls (n = 645) were derived fr om the same gastroenterology practice and were polyp-free at colonoscopy, D ietary intakes were estimated from a self-administered food-frequency quest ionnaire prior to colonoscopy, Multivariate adjusted odds ratios (ORs) and 95% confidence intervals for MTHFR status were 0.8 (0.6-1.2; CT versus CC w ild-type) and 0.9 (0.5-1.6; TT versus CC). In subgroup analyses stratified on dietary intakes of folate, vitamin B-12, vitamin B-6, or methionine, tho se with the TT genotype and either low intakes of folate or vitamin B-6 wer e at increased risk relative to those with normal or high vitamin intake. H owever, most 95% confidence intervals included 1.0, and no consistent trend s were observed. In contrast to our findings on colorectal adenomas, increa sing alcohol consumption was associated with an elevated risk of colorectal hyperplastic polyps, regardless of genotype. The MTHFR (C677T) variant gen otype does not appear to be related to risk of colorectal hyperplastic poly ps, and there is no convincing evidence that MTHFR shows a different relati on to risk, dependent on dietary intakes of nutrients related to its pathwa y.