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Risk analysis of prostate cancer in PRACTICAL, a multinational consortium, using 25 known prostate cancer susceptibility loci


Amin Al Olama, A and Benlloch, S and Antoniou, AC and Giles, GG and Severi, G and Neal, DE and Hamdy, FC and Donovan, JL and Muir, K and Schleutker, J and Henderson, BE and Haiman, CA and Schumacher, FR and Pashayan, N and Pharoah, PD and Ostrander, EA and Stanford, JL and Batra, J and Clements, JA and Chambers, SK and Weischer, M and Nordestgaard, BG and Ingles, SA and Sorensen, KD and Orntoft, TF and Park, JY and Cybulski, C and Maier, C and Doerk, T and Dickinson, JL and Cannon-Albright, L and Brenner, H and Rebbeck, TR and Zeigler-Johnson, C and Habuchi, T and Thibodeau, SN and Cooney, KA and Chappuis, PO and Hutter, P and Kaneva, RP and Foulkes, WD and Zeegers, MP and Lu, YJ and Zhang, HW and Stephenson, R and Cox, A and Southey, MC and Spurdle, AB and Fitzgerald, L and Leongamornlert, D and Saunders, E and Tymrakiewicz, M and Guy, M and Dadaev, T and Little, SJ and Govindasami, K and Sawyer, E and Wilkinson, R and Herkommer, K and Hopper, JL and Lophatonanon, A and Rinckleb, AE and Kote-Jarai, Z and Eeles, RA and Easton, DF, UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology, UK ProtecT Study Collaborators, PRACTICAL Consortium, Risk analysis of prostate cancer in PRACTICAL, a multinational consortium, using 25 known prostate cancer susceptibility loci, Cancer Epidemiology, Biomarkers and Prevention, 24, (7) pp. 1121-1129. ISSN 1055-9965 (2015) [Refereed Article]

Copyright Statement

Copyright 2015 American Association for Cancer Research

DOI: doi:10.1158/1055-9965.EPI-14-0317


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.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Oncology and carcinogenesis
Research Field:Cancer genetics
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Dickinson, JL (Professor Joanne Dickinson)
UTAS Author:Fitzgerald, L (Dr Liesel Fitzgerald)
ID Code:101882
Year Published:2015
Web of Science® Times Cited:46
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-07-15
Last Modified:2017-11-06
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