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Carcinogenesis Advance Access published online on April 8, 2009
Carcinogenesis, doi:10.1093/carcin/bgp086
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Association of Common Genetic Variants in SMAD7 and Risk of Colon Cancer

Cheryl L. Thompson1,4,5, Sarah J. Plummer6, Louise S. Acheson1,3,5, Thomas C. Tucker7, Graham Casey6 and Li Li1,2,4,5

1 Departments of Family Medicine
2 Epidemiology and Biostatistics
3 Reproductive Biology, Case Western Reserve University/University Hospitals Case Medical Center
4 The Case Center for Transdisciplinary Research on Energetics and Cancer
5 Case Comprehensive Cancer Center
6 Department of Preventive Medicine, University of Southern California
7 Cancer Control Program, University of Kentucky, Lexington

Corresponding Author: Li Li, MD, PhD, Department of Family Medicine, Case Western Reserve University, 11001 Cedar Avenue, Suite 306, Cleveland, OH 44106, Phone: 216-368-5437, Fax: 216-368-4348, li.li{at}case.edu

Two recent genome wide association studies (GWAS) identified three common variants in SMAD7 (rs4464148, rs4939827, and rs12953717) that confer modest susceptibility to colorectal cancer. Here, we replicated the association of rs4464148 with colon cancer in a population-based case-control study (561 cases and 721 controls). Compared to the TT genotype, those with CT and CC had an adjusted odds ratio (OR) and 95% confidence interval of 1.06 (0.82 – 1.38) and 1.86 (1.17 – 2.96), respectively (ptrend = 0.04). However, stratified analyses revealed that this association was limited to women only [OR = 1.25 (0.88 – 1.78) for CT, and OR = 2.76 (1.53 – 4.98) for CC, ptrend = 0.002, pinteraction = 0.08], which was not noted in any GWAS. Similarly, we found evidence for association with both rs4939827 and rs12953717 in women only (p = 0.007 in dominant rs4939827 model and p = 0.015 in recessive rs12953717 model), but not in men (p>0.05), and evidence of an interaction with gender (p = 0.015 for rs4939827 and p = 0.061 for rs12953717). Similar effect modification was found in haplotype analyses. Our data add evidence supporting these genetic variants as markers predisposing to colon cancer, specifically in women.

Received November 21, 2008; revised March 26, 2009; accepted April 4, 2009.


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