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American Journal of Epidemiology Advance Access originally published online on October 21, 2009
American Journal of Epidemiology 2009 170(10):1207-1221; doi:10.1093/aje/kwp275
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American Journal of Epidemiology © The Author 2009. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Meta- and Pooled Analyses of the Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism and Colorectal Cancer: A HuGE-GSEC Review

E. Taioli*, M. A. Garza, Y. O. Ahn, D. T. Bishop, J. Bost, B. Budai, K. Chen, F. Gemignani, T. Keku, C. S. P. Lima, L. Le Marchand, K. Matsuo, V. Moreno, J. Plaschke, M. Pufulete, S. B. Thomas, G. Toffoli, C. R. Wolf, C. G. Moore and J. Little

* Correspondence to Dr. Emanuela Taioli, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203 (e-mail: emanuela.taioli{at}downstate.edu).

Received for publication December 1, 2008. Accepted for publication August 6, 2009.

Worldwide, over 1 million cases of colorectal cancer (CRC) were reported in 2002, with a 50% mortality rate, making CRC the second most common cancer in adults. Certain racial/ethnic populations continue to experience a disproportionate burden of CRC. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been associated with a lower risk of CRC. The authors performed both a meta-analysis (29 studies; 11,936 cases, 18,714 controls) and a pooled analysis (14 studies; 5,068 cases, 7,876 controls) of the C677T MTHFR polymorphism and CRC, with stratification by racial/ethnic population and behavioral risk factors. There were few studies on different racial/ethnic populations. The overall meta-analysis odds ratio for CRC for persons with the TT genotype was 0.83 (95% confidence interval (CI): 0.77, 0.90). An inverse association was observed in whites (odds ratio = 0.83, 95% CI: 0.74, 0.94) and Asians (odds ratio = 0.80, 95% CI: 0.67, 0.96) but not in Latinos or blacks. Similar results were observed for Asians, Latinos, and blacks in the pooled analysis. The inverse association between the MTHFR 677TT polymorphism and CRC was not significantly modified by smoking status or body mass index; however, it was present in regular alcohol users only. The MTHFR 677TT polymorphism seems to be associated with a reduced risk of CRC, but this may not hold true for all populations.

colorectal neoplasms; epidemiologic methods; epidemiology; folic acid; genetics; genetic variation; methylenetetrahydrofolate reductase (NADPH2); MTHFR C677T

Abbreviations: CI, confidence interval; CINAHL, Cumulative Index to Nursing and Allied Health Literature; GSEC, Genetic Susceptibility to Environmental Carcinogens; HuGE, Human Genome Epidemiology; MTHFR, 5,10-methylenetetrahydrofolate reductase; OR, odds ratio

Editor's note: This article is also available on the Web site of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/default.htm).


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