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 Koushik, A. Articles by Hunter, D. J. Search for Related Content PubMed PubMed Citation Articles by Koushik, A. Articles by Hunter, D. J.

Nonsynonymous Polymorphisms in Genes in the One-Carbon Metabolism Pathway and Associations with Colorectal Cancer

¹ Department of Nutrition, ² Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health; ³ Department of Medical Oncology, Dana-Farber Cancer Institute; and ⁴ Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Requests for reprints: David Hunter, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115. Phone: 617-525-2755; Fax: 617-525-2008. E-mail: david.hunter{at}channing.harvard.edu

The Ala²²²Val single nucleotide polymorphism (SNP) in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in one-carbon metabolism, has been associated with colorectal cancer risk. Many enzymes are involved in one-carbon metabolism, and SNPs in the corresponding genes may play a role in colorectal carcinogenesis. We examined 24 nonsynonymous SNPs in 13 genes involved in the one-carbon metabolism pathway in relation to the risk of colorectal cancer in a case-control study nested in the Nurses' Health Study and the Health Professionals Follow-up Study cohorts. Among 376 men and women with colorectal cancer and 849 controls, a reduced risk of colorectal cancer was observed for Val/Val versus Ala carriers of MTHFR Ala²²²Val [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.43-1.00]. An increased risk was suggested for the variant carrier genotypes versus homozygous wild-type for betaine hydroxymethyltransferase Arg²³⁹Gln (OR, 1.40; 95% CI, 1.07-1.83) and two linked SNPs in methionine synthase reductase, Ser²⁸⁴Thr (OR, 1.85; 95% CI, 1.05-3.27) and Arg⁴¹⁵Cys (OR, 2.03; 95% CI, 1.15-3.56). The other SNPs were not associated with colorectal cancer risk. Also, none of the SNPs were associated with risk in subgroups of dietary methyl status or were jointly associated with colorectal cancer risk in combination with another SNP, except possibly SNPs in methionine synthase and transcobalamin II. However, these analyses of gene-diet interactions were limited in statistical power. Our results corroborate previous findings for MTHFR Ala²²²Val and suggest that other genes involved in one-carbon metabolism, particularly those that affect DNA methylation, may be associated with colorectal cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2408–17)

This article has been cited by other articles:

				M. Pande, J. Chen, C. I. Amos, P. M. Lynch, R. Broaddus, and M. L. Frazier Influence of Methylenetetrahydrofolate Reductase Gene Polymorphisms C677T and A1298C on Age-Associated Risk for Colorectal Cancer in a Caucasian Lynch Syndrome Population Cancer Epidemiol. Biomarkers Prev., September 1, 2007; 16(9): 1753 - 1759. [Abstract] [Full Text] [PDF]

				A. Hazra, K. Wu, P. Kraft, C. S. Fuchs, E. L. Giovannucci, and D. J. Hunter Twenty-four non-synonymous polymorphisms in the one-carbon metabolic pathway and risk of colorectal adenoma in the Nurses' Health Study Carcinogenesis, July 1, 2007; 28(7): 1510 - 1519. [Abstract] [Full Text] [PDF]