Letter abstract


Nature Genetics 40, 310 - 315 (2008)
Published online: 10 February 2008 | doi:10.1038/ng.91

Multiple loci identified in a genome-wide association study of prostate cancer

Gilles Thomas1, Kevin B Jacobs2, Meredith Yeager1,3, Peter Kraft4, Sholom Wacholder1, Nick Orr1, Kai Yu1, Nilanjan Chatterjee1, Robert Welch1,3, Amy Hutchinson1,3, Andrew Crenshaw1,3, Geraldine Cancel-Tassin5, Brian J Staats1,3, Zhaoming Wang1,3, Jesus Gonzalez-Bosquet1, Jun Fang1, Xiang Deng1,3, Sonja I Berndt1, Eugenia E Calle6, Heather Spencer Feigelson6, Michael J Thun6, Carmen Rodriguez6, Demetrius Albanes1, Jarmo Virtamo7, Stephanie Weinstein1, Fredrick R Schumacher4, Edward Giovannucci8, Walter C Willett8, Olivier Cussenot5, Antoine Valeri5, Gerald L Andriole9, E David Crawford10, Margaret Tucker1, Daniela S Gerhard11, Joseph F Fraumeni, Jr1, Robert Hoover1, Richard B Hayes1, David J Hunter1,4 & Stephen J Chanock1,12

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We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin—nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial prospective study—by testing 26,958 SNPs in four independent studies (total of 3,941 cases and 3,964 controls). In the combined joint analysis, we confirmed three previously reported loci (two independent SNPs at 8q24 and one in HNF1B (formerly known as TCF2 on 17q); P < 10-10). In addition, loci on chromosomes 7, 10 (two loci) and 11 were highly significant (between P < 7.31 times 10-13 and P < 2.14 times 10-6). Loci on chromosome 10 include MSMB, which encodes beta-microseminoprotein, a primary constituent of semen and a proposed prostate cancer biomarker, and CTBP2, a gene with antiapoptotic activity; the locus on chromosome 7 is at JAZF1, a transcriptional repressor that is fused by chromosome translocation to SUZ12 in endometrial cancer. Of the nine loci that showed highly suggestive associations (P < 2.5 times 10-5), four best fit a recessive model and included candidate susceptibility genes: CPNE3, IL16 and CDH13. Our findings point to multiple loci with moderate effects associated with susceptibility to prostate cancer that, taken together, in the future may predict high risk in select individuals.

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  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.
  2. Bioinformed Consulting Services, Gaithersburg, Maryland 20877, USA.
  3. Core Genotyping Facility, Advanced Technology Program, SAIC Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702, USA.
  4. Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
  5. CeRePP Hopital Tenon, Assistance Publique-Hôpitaux de Paris, Paris 75970, France.
  6. Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia 30329, USA.
  7. Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, Helsinki FIN-0030, Finland.
  8. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
  9. Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
  10. Department of Surgery, University of Colorado at Denver and Health Sciences Center, Denver, Colorado 80014, USA.
  11. Office of Cancer Genomics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.
  12. Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.

Correspondence to: Stephen J Chanock1,12 e-mail: chanocks@mail.nih.gov