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Genome-wide association study of prostate cancer identifies a second risk locus at 8q24.

Yeager, Meredith and Orr, Nick and Hayes, Richard B. and Jacobs, Kevin B. and Kraft, Peter and Wacholder, Sholom and Minichiello, Mark J. and Fearnhead, Paul and Kai, Yu and Chatterjee, Nilanjan and Zhaoming, Wang and Welch, Robert and Staats, Brian J. and Calle, Eugenia E. and Spencer-Fiegelsen, Heather and Thun, Michael J. and Rodriguez, Carmen and Albanes, Demetrius and Virtamo, Jarmo and Weinstein, Stephanie and Schumacher, Fredrick R. and Giovannucci, Edward and Willett, Walter C. and Cancel-Tassin, Geraldine and Cussenot, Olivier and Valeri, Antoine and Andriole, Gerald L. and Gelmann, Edward P. and Tucker, Margaret and Gerhard, Daniela S. and Fraumeni, Joseph F. and Hoover, Robert and Hunter, David J. and Chanock, Stephen J. and Thomas, Gilles (2007) Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nature Genetics, 39 (5). pp. 645-649.

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Abstract

Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 times 10-13; heterozygote odds ratio (OR): 1.26, 95% confidence interval (c.i.): 1.13–1.41; homozygote OR: 1.58, 95% c.i.: 1.40–1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 times 10-11; rs6983267 P = 6.62 times 10-10). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%).

Item Type: Article
Journal or Publication Title: Nature Genetics
Subjects: Q Science > QA Mathematics
Departments: Faculty of Science and Technology > Mathematics and Statistics
ID Code: 8184
Deposited By: Prof Paul Fearnhead
Deposited On: 15 Apr 2008 09:20
Refereed?: Yes
Published?: Published
Last Modified: 09 Oct 2013 15:41
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/8184

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