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Genetic Polymorphisms in Folate Metabolism and the Risk of Stomach Cancer

¹ Division of Cancer Epidemiology and Genetics and ² Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, Gaithersburg, Maryland; ³ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York; ⁴ Department of Epidemiology and Biostatistics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; ⁵ Division of Cancer Epidemiology and Prevention, Cancer Center and M. Sklosowska-Curie Institute of Oncology, Warsaw, Poland; and ⁶ Center for the Biology of Natural Systems, Queens College, City University of New York, Flushing, New York

Requests for reprints: Fang Fang Zhang, Columbia University, 722 West 168th Street, New York, 10032 NY. Phone: 212-342-5439; Fax: 212-305-9413. E-mail: fz2004{at}columbia.edu

Folate deficiency has been implicated in the etiology of stomach cancer through abnormal DNA methylation and disrupted DNA synthesis and repair. Enzyme-coding genes involved in folate metabolism are often polymorphic. In a population-based study of 305 cases and 427 controls in Warsaw, Poland, we evaluated the risk of stomach cancer in relation to polymorphisms in folate-metabolizing genes, including MTHFR (Ex5+79C>T and Ex8–62A>C), MTR (Ex26–20A>G), and MTRR (Ex2–64A>G, Ex5+123C>T, Ex15+572C>T, Ex15–405A>T, Ex9–85C>T, Ex15–526G>A, and Ex14+14C>T). Polymorphisms in the MTHFR gene were not associated with stomach cancer risk. No notable effect was found for polymorphisms in MTR or MTRR either, although MTR Ex26–20 A>G and MTRR Ex5+123C>T polymorphisms were associated with a borderline increased risk of stomach cancer (MTR Ex26–20A>G, AG/GG versus AA: odds ratio, 1.35; 95% confidence interval, 0.96-1.90; MTRR Ex5+123C>T, CT/TT versus CC: odds ratio, 1.30; 95% confidence interval, 0.93-1.82). We did not find significant interactions between polymorphisms in MTHFR, MTR, and MTRR genes and dietary folate and alcohol consumption. Our study did not identify strong genetic determinants in the folate metabolism pathway for stomach cancer risk. (Cancer Epidemiol Biomarkers Prev 2007;16(1):115–21)

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