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Lack of Association between the C677T MTHFR Polymorphism and Colorectal Hyperplastic Polyps¹

Cancer Prevention Research Program [C. M. U., S. A. A. B., Y. Y., J. D. P.] and Programs in Cancer Biology [J. B., C. C.] and Epidemiology [ S. M. S.], Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; Department of Epidemiology, University of Washington, Seattle, Washington 98195 [C. M. U., S. M. S., S. A. A. B., J. D. P.]; Wageningen Agricultural University, 6703 HA Wageningen, the Netherlands [E. K.]; South Carolina Cancer Center, University of South Carolina, Columbia, South Carolina 29203 [R. B.]; and University of Minnesota, Minneapolis, Minnesota 55454 [L. F.]

Colorectal hyperplastic polyps are benign lesions that share many risk factors with colorectal adenomas and cancers. Low folate intakes are associated with an increased risk of colon cancer. The enzyme 5,10-methylene-tetrahydrofolate 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) and colorectal hyperplastic polyps within the Minnesota Cancer Prevention Research Unit case-control study. Cases (n = 200) were diagnosed with colonoscopically confirmed hyperplastic polyps; controls (n = 645) were derived from the same gastroenterology practice and were polyp-free at colonoscopy. Dietary intakes were estimated from a self-administered food-frequency questionnaire 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 wild-type) and 0.9 (0.5–1.6; TT versus CC). In subgroup analyses stratified on dietary intakes of folate, vitamin B₁₂, vitamin B₆, or methionine, those with the TT genotype and either low intakes of folate or vitamin B₆ were at increased risk relative to those with normal or high vitamin intake. However, most 95% confidence intervals included 1.0, and no consistent trends were observed. In contrast to our findings on colorectal adenomas, increasing alcohol consumption was associated with an elevated risk of colorectal hyperplastic polyps, regardless of genotype. The MTHFR (C677T) variant genotype does not appear to be related to risk of colorectal hyperplastic polyps, and there is no convincing evidence that MTHFR shows a different relation to risk, dependent on dietary intakes of nutrients related to its pathway.

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