Investigation of the colorectal cancer susceptibility region on chromosome 8q24.21 in a large German case-control sample.

Clemens Schafmayer, Stephan Buch, Henry Völzke, Witigo von Schönfels, Jan Hendrik Egberts, Bodo Schniewind, Mario Brosch, Andreas Ruether, Andre Franke, Micaela Mathiak, Bence Sipos, Tobias Henopp, Jasmin Catalcali, Stephan Hellmig, Abdou ElSharawy, Alexander Katalinic, Markus M Lerch, Ulrich John, Ulrich R Fölsch, Fred Fändrich, Holger Kalthoff, Stefan Schreiber, Michael Krawczak, Jürgen Tepel, Jochen Hampe
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International journal of cancer. Predictive oncology = Journal international du cancer. Predictive oncology
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Human chromosome 8q24.21 has been implicated as a susceptibility region for colorectal cancer (CRC) as a result of genome-wide association and candidate gene studies. To assess the impact of molecular variants at 8q24.21 upon the CRC risk of German individuals and to refine the disease-associated region, a total of 2,713 patients with operated CRC (median age at diagnosis: 63 years) were compared with 2,718 sex-matched control individuals (median age at inclusion: 65 years). Information on microsatellite instability in tumors was available for 901 patients. Association analysis of SNPs rs10505477 and rs6983267 yielded allelic p-values of 1.42 x 10(-7) and 2.57 x 10(-7), respectively. For both polymorphisms, the odds ratio was estimated to be 1.50 (95% CI: 1.29-1.75) under a recessive disease model. The strongest candidate interval, outside of which significance dropped by more than 4 orders of magnitude, was delineated by SNPs rs10505477 and rs7014346 and comprised 17 kb. In a subgroup analysis, the disease association was found to be more pronounced in MSI-stable tumors (odds ratio: 1.71). Our study confirms the role of genetic variation at 8q24.21 as a risk factor for CRC and localizes the corresponding susceptibility gene to a 17 kb candidate region.