Journal Article

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

Fearnhead, Paul, Wacholder, Sholom, Schumacher, Fredrick R, Staats, Brian J, Welch, Robert, Rodriguez, Carmen, Andriole, Gerald L, Fraumeni, Joseph F, Cancel-Tassin, Geraldine, Calle, Eugenia E, Tucker, Margaret, Hoover, Robert, Virtamo, Jarmo, Albanes, Demetrius, Weinstein, Stephanie, Hayes, Richard B, Feigelson, Heather Spencer, Thomas, Gilles, Orr, Nick, Jacobs, Kevin B, Willett, Walter C, Yeager, Meredith, Yu, Kai, Cussenot, Olivier, Chatterjee, Nilanjan, Gelmann, Edward P, Gerhard, Daniela S, Chanock, Stephen J, Thun, Michael J, Valeri, Antoine, Kraft, Peter, Giovannucci, Edward, Wang, Zhaoming, Minichiello, Mark J, Hunter, David J

2007

Overview

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 × 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 × 10 −11 ; rs6983267 P = 6.62 × 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%).

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: African Americans / Agriculture / Animal Genetics and Genomics / Base Sequence / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Chromosomes / Chromosomes, Human, Pair 8 - genetics / Classical genetics, quantitative genetics, hybrids / Diagnosis / Ethnic Groups - genetics / European Continental Ancestry Group / Fundamental and applied biological sciences. Psychology / Gene Frequency / Gene Function / Genetic markers / Genetic Predisposition to Disease - genetics / Genetic Variation / Genetics of eukaryotes. Biological and molecular evolution / Genomics / Genomics - methods / Genotype / Gynecology. Andrology. Obstetrics / Haplotypes - genetics / Health risks / Human Genetics / Humans / letter / Male / Male genital diseases / Medical sciences / Methods, theories and miscellaneous / Molecular Sequence Data / Nephrology. Urinary tract diseases / Odds Ratio / Physiological aspects / Polymorphism, Single Nucleotide / Prostate cancer / Prostatic Neoplasms - genetics / Risk Factors / Single nucleotide polymorphisms / Tumors / Tumors of the urinary system / United States / Urinary tract. Prostate gland