Abstract

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 × 10−13 and P < 2.14 × 10−6). Loci on chromosome 10 include MSMB, which encodes β-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 × 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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Acknowledgements

The Prostate Lung Colorectal Ovarian Cancer Screening Trial (PLCO) was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and by contracts from the Division of Cancer Prevention, National Cancer Institute, US National Institutes of Health, Department of Health and Human Services. The Health Professionals Follow-up Study (HPFS) study is supported by the US National Institutes of Health grant CA55075 and U01CA098233. The American Cancer Society (ACS) study is supported by U01 CA098710. The Alpha Tocopherol Beta-Carotene Cancer Prevention study (ATBC) Study is supported by the Intramural Research Program of the National Cancer Institute, NIH, and by US Public Health Service contracts N01-CN-45165, N01-RC-45035, and N01-RC-37004 from the National Cancer Institute, Department of Health and Human Services. F.R.S. is supported by a NRSA training-grant (T32 CA 09001). Centre de Recherche pour les Pathologies Prostatiques (CeRePP) thanks J.P.B. and Generali for their charitable donations which have contributed to this project. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Author information

Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.

    • Gilles Thomas
    • , Meredith Yeager
    • , Sholom Wacholder
    • , Nick Orr
    • , Kai Yu
    • , Nilanjan Chatterjee
    • , Robert Welch
    • , Amy Hutchinson
    • , Andrew Crenshaw
    • , Brian J Staats
    • , Zhaoming Wang
    • , Jesus Gonzalez-Bosquet
    • , Jun Fang
    • , Xiang Deng
    • , Sonja I Berndt
    • , Demetrius Albanes
    • , Stephanie Weinstein
    • , Margaret Tucker
    • , Joseph F Fraumeni Jr
    • , Robert Hoover
    • , Richard B Hayes
    • , David J Hunter
    •  & Stephen J Chanock
  2. Bioinformed Consulting Services, Gaithersburg, Maryland 20877, USA.

    • Kevin B Jacobs
  3. Core Genotyping Facility, Advanced Technology Program, SAIC Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702, USA.

    • Meredith Yeager
    • , Robert Welch
    • , Amy Hutchinson
    • , Andrew Crenshaw
    • , Brian J Staats
    • , Zhaoming Wang
    •  & Xiang Deng
  4. Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

    • Peter Kraft
    • , Fredrick R Schumacher
    •  & David J Hunter
  5. CeRePP Hopital Tenon, Assistance Publique-Hôpitaux de Paris, Paris 75970, France.

    • Geraldine Cancel-Tassin
    • , Olivier Cussenot
    •  & Antoine Valeri
  6. Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia 30329, USA.

    • Eugenia E Calle
    • , Heather Spencer Feigelson
    • , Michael J Thun
    •  & Carmen Rodriguez
  7. Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, Helsinki FIN-0030, Finland.

    • Jarmo Virtamo
  8. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

    • Edward Giovannucci
    •  & Walter C Willett
  9. Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri 63108, USA.

    • Gerald L Andriole
  10. Department of Surgery, University of Colorado at Denver and Health Sciences Center, Denver, Colorado 80014, USA.

    • E David Crawford
  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.

    • Daniela S Gerhard
  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.

    • Stephen J Chanock

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https://doi.org/10.1038/ng.91

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