Authors

Ali Amin Al Olama, University of Cambridge
Sara Benlloch, University of Cambridge
Antonis C Antoniou, University of Cambridge
Graham G Giles, Cancer Council Victoria
Gianluca Severi, Cancer Council Victoria
David E Neal, University of Cambridge
Freddie C Hamdy, University of Oxford
Jenny L Donovan, University of Bristol
Kenneth Muir, University of Manchester
Johanna Schleutker, University of Turku
Brian E Henderson, Keck School of Medicine
Christopher Haiman, Keck School of Medicine
Fredrick R Schumacher, Keck School of Medicine
Nora Pashayan, University of Cambridge
Paul D P Pharoah, University of Cambridge
Elaine A Ostrander, National Human Genome Research Institute
Janet L Stanford, University of Washington
Jyotsna Batra, Queensland University of Technology
Judith A Clements, Queensland University of Technology
Suzanne K Chambers, Griffith University
Maren Weischer, Copenhagen University Hospital
Børge G Nordestgaard, Copenhagen University Hospital
Sue A Ingles, Keck School of Medicine
Karina D Sorensen, Aarhus University Hospital
Torben F Orntoft, Aarhus University Hospital
Jong Y Park, H. Lee Moffitt Cancer Centre
Cezary Cybulski, Pomeranian Medical University
Christiane Maier, University Hospital Ulm
Thilo Doerk, Hannover Biomedical Research School
Joanne L Dickinson, University of Tasmania
Lisa Cannon-Albright, University of Utah School of Medicine
Hermann Brenner, German Cancer Consortium (DKTK)
Timothy R Rebbeck, University of Pennsylvania
Charnita Zeigler-Johnson, Thomas Jefferson UniversityFollow
Tomonori Habuchi, Akita University School of Medicine
Stephen N Thibodeau, Mayo Clinic
Kathleen A Cooney, University of Michigan Medical School
Pierre O Chappuis, Geneva University Hospitals
Pierre Hutter, Hopital Cantonal Universitaire de Geneve
Radka P Kaneva, Medical University-Sofia
William D Foulkes, McGill University
Maurice P Zeegers, Maastricht University Medical Centre
Yong-Jie Lu, Queen Mary University of London
Hong-Wei Zhang, Second Military Medical University
Robert Stephenson, University of Utah School of Medicine
Angela Cox, University of Sheffield
Melissa C Southey, University of Melbourne
Amanda B Spurdle, Molecular Cancer Epidemiology Laboratory
Liesel FitzGerald, Cancer Council Victoria
Daniel Leongamornlert, Institute of Cancer Research
Edward Saunders, Institute of Cancer Research
Malgorzata Tymrakiewicz, Institute of Cancer Research
Michelle Guy, Institute of Cancer Research
Tokhir Dadaev, Institute of Cancer Research
Sarah J Little, Institute of Cancer Research
Koveela Govindasami, Institute of Cancer Research
Emma Sawyer, Institute of Cancer Research
Rosemary Wilkinson, Institute of Cancer Research
Kathleen Herkommer, Technical University Munich
John L Hopper, University of Melbourne
Aritaya Lophatonanon, University of Warwick
Antje E Rinckleb, University Hospital Ulm
Zsofia Kote-Jarai, Institute of Cancer Research
Rosalind A Eeles, Institute of Cancer Research
Douglas F Easton, University of Cambridge

Document Type

Article

Publication Date

7-1-2015

Comments

This article has been peer reviewed. It is the author’s final published version in Cancer Epidemiology Biomarkers and Prevention Volume 24, Issue 7, July 2015, Pages 1121-1129.

The published version is available at DOI: 10.1158/1055-9965.EPI-14-0317. Copyright © American Association for Cancer Research Inc.

Abstract

BACKGROUND: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer.

METHODS: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history.

RESULTS: The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09).

CONCLUSIONS: Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles.

IMPACT: We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.

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