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Multicenter Study
. 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

Ali Amin Al Olama  1 , Sara Benlloch  2 , Antonis C Antoniou  2 , Graham G Giles  3 , Gianluca Severi  4 , David E Neal  5 , Freddie C Hamdy  6 , Jenny L Donovan  7 , Kenneth Muir  8 , Johanna Schleutker  9 , Brian E Henderson  10 , Christopher A Haiman  10 , Fredrick R Schumacher  10 , Nora Pashayan  11 , Paul D P Pharoah  2 , Elaine A Ostrander  12 , Janet L Stanford  13 , Jyotsna Batra  14 , Judith A Clements  14 , Suzanne K Chambers  15 , Maren Weischer  16 , Børge G Nordestgaard  16 , Sue A Ingles  10 , Karina D Sorensen  17 , Torben F Orntoft  17 , Jong Y Park  18 , Cezary Cybulski  19 , Christiane Maier  20 , Thilo Doerk  21 , Joanne L Dickinson  22 , Lisa Cannon-Albright  23 , Hermann Brenner  24 , Timothy R Rebbeck  25 , Charnita Zeigler-Johnson  26 , Tomonori Habuchi  27 , Stephen N Thibodeau  28 , Kathleen A Cooney  29 , Pierre O Chappuis  30 , Pierre Hutter  31 , Radka P Kaneva  32 , William D Foulkes  33 , Maurice P Zeegers  34 , Yong-Jie Lu  35 , Hong-Wei Zhang  36 , Robert Stephenson  37 , Angela Cox  38 , Melissa C Southey  39 , Amanda B Spurdle  40 , Liesel FitzGerald  41 , Daniel Leongamornlert  42 , Edward Saunders  42 , Malgorzata Tymrakiewicz  42 , Michelle Guy  42 , Tokhir Dadaev  42 , Sarah J Little  42 , Koveela Govindasami  42 , Emma Sawyer  42 , Rosemary Wilkinson  42 , Kathleen Herkommer  43 , John L Hopper  44 , Aritaya Lophatonanon  45 , Antje E Rinckleb  20 , Zsofia Kote-Jarai  42 , Rosalind A Eeles, Douglas F Easton  1 ; UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology; UK ProtecT Study Collaborators; PRACTICAL Consortium
Collaborators, Affiliations
Multicenter Study

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

Ali Amin Al Olama et al. Cancer Epidemiol Biomarkers Prev. 2015 Jul.

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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Conflict of interest statement

Conflict of Interest: There is no conflict of interest.

Figures

Figure 1
Figure 1
Absolute risk of PrCa by age in men with family history.
Figure 2
Figure 2
Absolute risk of PrCa by age in men with no family history.
See this image and copyright information in PMC

Comment in

References

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