Carcinogenesis Advance Access originally published online on April 8, 2009
Carcinogenesis 2009 30(6):982-986; doi:10.1093/carcin/bgp086
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Association of common genetic variants in SMAD7 and risk of colon cancer
1 Department of Family Medicine, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, OH 44106, USA
2 Case Center for Transdisciplinary Research on Energetics and Cancer
3 Case Comprehensive Cancer Center, Cleveland, OH 44106, USA
4 Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90089, USA
5 Department of Reproductive Biology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, OH 44106, USA
6 Cancer Control Program, Markey Cancer Center, University of Kentucky, Lexington, KY 40504, USA
7 Department of Epidemiology and Biostatistics, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, OH 44106, USA
* To whom correspondence should be addressed. Department of Family Medicine, Case Western Reserve University, 11001 Cedar Avenue, Suite 306, Cleveland, OH 44106, USA. Tel: +1 216 368 5437; Fax: +1 216 368 4348; Email: 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 with 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.
Abbreviations: CI, confidence interval; GWAS, genome-wide association studies; NSAID, non-steroidal anti-inflammatory drug; OR, odds ratio; SNP, single nucleotide polymorphism; TGF-β, transforming growth factor beta
Received November 21, 2008; revised March 26, 2009; accepted April 4, 2009.