Human Molecular Genetics Advance Access originally published online on June 4, 2008
Human Molecular Genetics 2008 17(17):2665-2672; doi:10.1093/hmg/ddn166
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Published by Oxford University Press 2008
Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk
1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA 2 Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA 3 Department of Epidemiology, University of Washington, Seattle, WA 98195, USA 4 Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA 5 Advanced Technology Program, SAIC-Frederick, Inc., National Cancer Institute Frederick, Frederick, MD 21702, USA 6 Department of Medicine 7 Department of Epidemiology 8 University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15260, USA 9 Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA 10 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA 11 Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA
* To whom correspondence should be addressed at: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, EPS 8116, MSC 7240, Bethesda, MD 20892-7240, USA. Tel: +1 3015947898; Fax: +1 3014021819; Email: berndts{at}mail.nih.gov
Received March 7, 2008; Revised May 13, 2008; Accepted June 3, 2008
Several different genetic variants at chromosome 8q24 have been related to prostate, breast and colorectal cancer risk with evidence of region-specific risk differentials for various tumor types. We investigated the association between 15 polymorphisms located in 8q24 regions associated with cancer risk in a pooled analysis of 2587 colorectal adenoma cases, 547 colorectal cancer cases and 2798 controls of European descent from four studies. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations. Three polymorphisms (rs10808555, rs6983267 and rs7837328) located between 128.47 and 128.54 Mb were found to be associated with colorectal tumor risk. The association was strongest for the previously reported rs6983267 variant and was similar for both adenoma (ORper allele = 1.16, 95% CI: 1.07–1.25, P = 0.0002) and cancer (OR per allele = 1.17, 95% CI: 1.01–1.35, P = 0.03). The strength of the association of the regional haplotype containing variant alleles at rs10808555, rs6983267 and rs7837328 but not rs10505476 was greater than that of any single variant of both adenoma (OR = 1.27, P = 0.0001) and cancer (OR = 1.26, P = 0.03). The risk associated with rs6983267 was stronger for multiple adenomas (ORper allele = 1.29, P = 5.6 x 10–6) than for single adenoma (ORper allele = 1.10, P = 0.03) with Pheterogeneity = 0.008. This study confirms the association between colorectal neoplasia and the 8q24 polymorphisms located between 128.47 and 128.54 Mb and suggests a role for these variants in the formation of multiple adenomas.
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