This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goode, E. L. Articles by Ulrich, C. M. Search for Related Content PubMed PubMed Citation Articles by Goode, E. L. Articles by Ulrich, C. M.

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

¹ Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington; and ² Department of Epidemiology, University of Washington, Seattle, Washington

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 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.

This article has been cited by other articles:

				J. C. Figueiredo, A. J. Levine, M. V. Grau, O. Midttun, P. M. Ueland, D. J. Ahnen, E. L. Barry, S. Tsang, D. Munroe, I. Ali, et al. Vitamins B2, B6, and B12 and Risk of New Colorectal Adenomas in a Randomized Trial of Aspirin Use and Folic Acid Supplementation Cancer Epidemiol. Biomarkers Prev., August 1, 2008; 17(8): 2136 - 2145. [Abstract] [Full Text] [PDF]

				C. M. Ulrich, K. Curtin, J. D. Potter, J. Bigler, B. Caan, and M. L. Slattery Polymorphisms in the Reduced Folate Carrier, Thymidylate Synthase, or Methionine Synthase and Risk of Colon Cancer Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2509 - 2516. [Abstract] [Full Text] [PDF]

				Z. Zhang, Y. Xu, J. Zhou, X. Wang, L. Wang, X. Hu, J. Guo, Q. Wei, and H. Shen Polymorphisms of thymidylate synthase in the 5'- and 3'-untranslated regions associated with risk of gastric cancer in South China: a case-control analysis Carcinogenesis, October 1, 2005; 26(10): 1764 - 1769. [Abstract] [Full Text] [PDF]

				C.-X. Yang, K. Matsuo, H. Ito, M. Shinoda, S. Hatooka, K. Hirose, K. Wakai, T. Saito, T. Suzuki, T. Maeda, et al. Gene-environment interactions between alcohol drinking and the MTHFR C677T polymorphism impact on esophageal cancer risk: results of a case-control study in Japan Carcinogenesis, July 1, 2005; 26(7): 1285 - 1290. [Abstract] [Full Text] [PDF]

				W. Zhang, A. Braun, Z. Bauman, H. Olteanu, P. Madzelan, and R. Banerjee Expression Profiling of Homocysteine Junction Enzymes in the NCI60 Panel of Human Cancer Cell Lines Cancer Res., February 15, 2005; 65(4): 1554 - 1560. [Abstract] [Full Text] [PDF]

				Z. Zhang, Q. Shi, E. M. Sturgis, M. R. Spitz, W. K. Hong, and Q. Wei Thymidylate Synthase 5'- and 3'-Untranslated Region Polymorphisms Associated with Risk and Progression of Squamous Cell Carcinoma of the Head and Neck Clin. Cancer Res., December 1, 2004; 10(23): 7903 - 7910. [Abstract] [Full Text] [PDF]

				Z. Kemp, C. Thirlwell, O. Sieber, A. Silver, and I. Tomlinson An update on the genetics of colorectal cancer Hum. Mol. Genet., October 1, 2004; 13(suppl_2): R177 - R185. [Abstract] [Full Text] [PDF]