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Cancer Epidemiol Biomarkers Prev. 2015 Jul;24(7):1121-9. doi: 10.1158/1055-9965.EPI-14-0317. Epub 2015 Apr 2.

Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci.

Author information

1
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom. aa461@medschl.cam.ac.uk dfe20@medschl.cam.ac.uk.
2
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
3
Cancer Epidemiology Centre, the Cancer Council Victoria, Carlton, Victoria, Australia. Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Melbourne, Victoria, Australia.
4
Cancer Epidemiology Centre, the Cancer Council Victoria, Carlton, Victoria, Australia.
5
University of Cambridge, Department of Oncology, Addenbrooke's Hospital, Cambridge, United Kingdom. Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, United Kingdom.
6
Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom. Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
7
School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
8
The University of Manchester, Centre for Epidemiology, Institute of Population Health, Manchester, United Kingdom. University of Warwick, University House, Coventry, United Kingdom.
9
Institute of Biomedical Technology/BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland. Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.
10
Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Centre, Los Angeles, California.
11
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom. University College London, Department of Applied Health Research, London, United Kingdom.
12
National Human Genome Research Institute, NIH, Bethesda, Maryland.
13
Division of Public Health Sciences, Fred Hutchinson Cancer Research Centre, Seattle, Washington. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.
14
Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, Queensland, Australia.
15
Griffith Health Institute, Griffith University, Gold Coast, Queensland, Australia. Cancer Council Queensland, Brisbane, Queensland, Australia. Prostate Cancer Foundation of Australia, Sydney, Australia.
16
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
17
Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus N, Denmark.
18
Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Centre, Tampa, Florida.
19
International Hereditary Cancer Centre, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
20
Department of Urology, University Hospital Ulm, Ulm, Germany.
21
Hannover Biomedical Research School, Hannover, Germany.
22
University of Tasmania, Menzies Research Institute Tasmania, Hobart, Tasmania, Australia.
23
Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah. George E. Wahlen Department of Veterans Affairs Medical Centre, Salt Lake City, Utah.
24
Division of Clinical Epidemiology and Ageing Research, German Cancer Research Centre (DKFZ), Heidelberg, Germany. German Cancer Consortium (DKTK), Heidelberg, Germany.
25
University of Pennsylvania, Philadelphia, Pennsylvania.
26
Division of Population Sciences, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
27
Department of Urology, Akita University School of Medicine, Akita, Japan.
28
Mayo Clinic, Rochester, Minnesota.
29
Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, Michigan.
30
Divisions of Oncology and Genetic Medicine, Geneva University Hospitals, Geneva, Switzerland.
31
Hopital Cantonal Universitaire de Geneve, Geneva, Switzerland.
32
Department of Medical Chemistry and Biochemistry, Molecular Medicine Centre, Medical University-Sofia, Sofia, Bulgaria.
33
McGill University, Montreal, Quebec, Canada.
34
Department of Complex Genetics, Cluster of Genetics and Cell Biology, NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Centre+, Maastricht, the Netherlands.
35
Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, London, United Kingdom.
36
Second Military Medical University, Shanghai, P.R. China.
37
Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah.
38
CR-UK/YCR Sheffield Cancer Research Centre, University of Sheffield, Sheffield, United Kingdom.
39
Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
40
Molecular Cancer Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
41
Cancer Council Victoria, Cancer Epidemiology Centre, Melbourne, Victoria, Australia.
42
The Institute of Cancer Research, London, United Kingdom.
43
Department of Urology, Technical University Munich, Munich, Germany.
44
Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Melbourne, Victoria, Australia.
45
University of Warwick, University House, Coventry, United Kingdom. Institute of Biomedical Technology/BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland.

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.

Comment in

PMID:
25837820
PMCID:
PMC4491026
DOI:
10.1158/1055-9965.EPI-14-0317
[Indexed for MEDLINE]
Free PMC Article

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