Short Communication Methionine Synthase D919G Polymorphism, Folate Metabolism, and Colorectal Adenoma Risk

Methionine synthase [5-methyltetrahydrofolatehomocysteine S-methyltransferase (MTR)] is involved in folate-mediated one-carbon metabolism, a pathway known to play a role in colorectal carcinogenesis. We investigated whether the MTR D919G polymorphism was associated with risk of colorectal adenoma in a colonoscopy-based study of 513 cases and 609 controls from Minneapolis, MN. Adenoma risk appeared nonsignificantly increased among women with DG or GG genotype [adjusted odds ratio (OR) versus DD, 1.4; 95% confidence interval (CI), 0.9–2.1] but not men (OR, 1.0; 95% CI, 0.7–1.5). An interaction with methionine intake was observed among women, such that low versus high intake was associated with a 2.3-fold increased risk only among those with DG or GG genotype (95% CI, 1.1–4.9; P for interaction 0.05). Similarly, risk associated with alcohol intake was not elevated among women with the DD genotype; however, consumption of >7 g of alcohol/ day versus none was associated with an increased risk among women with DG or GG genotype (adjusted OR, 2.5; 95% CI, 1.4–4.4; P for interaction 0.03). An interaction between MTR D919G and the thymidylate synthase (TS or TYMS) 3 -untranslated region polymorphism 1494del6 was also observed among women (P for interaction 0.007). No evidence of interaction with intake of folate, vitamin B12, or vitamin B6 or with genotype at MTHFR C677T or the TS enhancer region 28-bp repeat polymorphism was seen. These findings add to what is known about the complexities of genetic variations in one-carbon-metabolizing enzymes in relation to colorectal carcinogenesis.