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

Research output: Contribution to journalJournal article

Published

  • Meredith Yeager
  • Nick Orr
  • Richard B. Hayes
  • Kevin B. Jacobs
  • Peter Kraft
  • Sholom Wacholder
  • Mark J. Minichiello
  • Yu Kai
  • Nilanjan Chatterjee
  • Wang Zhaoming
  • Robert Welch
  • Brian J. Staats
  • Eugenia E. Calle
  • Heather Spencer-Fiegelsen
  • Michael J. Thun
  • Carmen Rodriguez
  • Demetrius Albanes
  • Jarmo Virtamo
  • Stephanie Weinstein
  • Fredrick R. Schumacher
  • Edward Giovannucci
  • Walter C. Willett
  • Geraldine Cancel-Tassin
  • Olivier Cussenot
  • Antoine Valeri
  • Gerald L. Andriole
  • Edward P. Gelmann
  • Margaret Tucker
  • Daniela S. Gerhard
  • Joseph F. Fraumeni
  • Robert Hoover
  • David J. Hunter
  • Stephen J. Chanock
  • Gilles Thomas
Journal publication date05/2007
JournalNature Genetics
Journal number5
Volume39
Number of pages5
Pages645-649
Original languageEnglish

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%).