Methionine synthase D919G polymorphism, folate metabolism, and colorectal adenoma risk.

Abstract

Methionine synthase [5-methyltetrahydrofolate-homocysteine 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 B(12), or vitamin B(6) 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.

• Authors: Ellen L Goode, John D Potter, Jeannette Bigler, Cornelia M Ulrich
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 13 Issue 1 Pg. 157-62 (Jan 2004) ISSN: 1055-9965 [Print] United States
• PMID: 14744749 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Folic Acid
• 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase

Topics

• 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase (genetics)
• Adenoma (genetics)
• Adult
• Aged
• Case-Control Studies
• Colorectal Neoplasms (genetics)
• Diet
• Female
• Folic Acid (metabolism)
• Genotype
• Humans
• Logistic Models
• Male
• Middle Aged
• Minnesota
• Polymorphism, Genetic
• Risk Factors
• Sex Distribution