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

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 x 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 x 10(-11); rs6983267 P = 6.62 x 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%).

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