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Research Paper

Genetic Variation in 8q24 Associated with Risk of Colorectal Cancer

Stephen B. Gruber, Victor Moreno, Laura S. Rozek, Hedy S. Rennert, Flavio Lejbkowicz, Joseph D. Bonner, Joel K. Greenson, Thomas J. Giordano, Eric R. Fearon and Gad Rennert

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Chromosome 8q24 harbors oncogenes known to be involved in pathogenesis of colorectal cancer (CRC) as well as uncharacterized genetic variants that have recently been shown to influence inherited risk of prostate cancer. In a population-based case-control study of colorectal cancer in northern Israel, we investigated the association between variation in 8q24 and risk of CRC. Among 1,861 incident cases and 1,937 population-based controls matched on age, gender, ethnicity, and clinic, rs10505477 was associated with risk of CRC in a dominant model, with an odds ratio = 1.23, 95% confidence interval = 1.05 -1.43, (p=0.008). This association was independently validated in an analysis of cancer among relatives of carriers of the risk allele, with a hazard ratio of 3.2 (95% bootstrap CI = 1.16 – 17.8). Genetic variation at rs10505477 on 8q24 potentially accounts for 14% of CRC in this population and should be replicated in other studies.

Authors

Stephen B. Gruber

Departments of Internal Medicine, Epidemiology, and Human Genetics, University of Michigan Medical School, Ann Arbor, MI

Victor Moreno

Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI; Catalan Institute of Oncology (ICO), Barcelona, Spain,

Laura S. Rozek

Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI

Hedy S. Rennert

CHS National Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center; B. Rappaport Faculty of Medicine, Technion %u2013 Israel Institute of Technology, Haifa, Israel,

Flavio Lejbkowicz

5CHS National Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center; B. Rappaport Faculty of Medicine, Technion %u2013 Israel Institute of Technology, Haifa, Israel,

Joseph D. Bonner

Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI

Joel K. Greenson

Department of Pathology, University of Michigan, Ann Arbor, MI

Thomas J. Giordano

Department of Pathology, University of Michigan, Ann Arbor, MI

Eric R. Fearon

Departments of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI; Department of Pathology, University of Michigan, Ann Arbor, MI

Gad Rennert

5CHS National Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center; B. Rappaport Faculty of Medicine, Technion %u2013 Israel Institute of Technology, Haifa, Israel

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.