TY - JOUR
T1 - Risk analysis of prostate cancer in practical, a multinational consortium, using 25 known prostate cancer susceptibility loci
AU - UK Genetic Prostate Cancer Study Collaborators/ British Association of Urological Surgeons' Section of Oncology, UK Protect Study Collaborators, PRACTICAL Consortium
AU - Al Olama, Ali Amin
AU - Benlloch, Sara
AU - Antoniou, Antonis C.
AU - Giles, Grahamg
AU - Severi, Gianluca
AU - Neal, David E.
AU - Hamdy, Freddie C.
AU - Donovan, Jenny L.
AU - Muir, Kenneth
AU - Schleutker, Johanna
AU - Henderson, Brian E.
AU - Haiman, Christopher A.
AU - Schumacher, Fredrick R.
AU - Pashayan, Nora
AU - Pharoah, Paul D.P.
AU - Ostrander, Elaine A.
AU - Stanford, Janet L.
AU - Batra, Jyotsna
AU - Clements, Judith A.
AU - Chambers, Suzanne K.
AU - Weischer, Maren
AU - Nordestgaard, Børge G.
AU - Ingles, Sue A.
AU - Sorensen, Karina D.
AU - Orntoft, Torben F.
AU - Park, Jong Y.
AU - Cybulski, Cezary
AU - Maier, Christiane
AU - Doerk, Thilo
AU - Dickinson, Joanne L.
AU - Cannon-Albright, Lisa
AU - Brenner, Hermann
AU - Rebbeck, Timothy R.
AU - Zeigler-Johnson, Charnita
AU - Habuchi, Tomonori
AU - Thibodeau, Stephen N.
AU - Cooney, Kathleen A.
AU - Chappuis, Pierre O.
AU - Hutter, Pierre
AU - Kaneva, Radka P.
AU - Foulkes, William D.
AU - Zeegers, Maurice P.
AU - Lu, Yong Jie
AU - Zhang, Hong Wei
AU - Stephenson, Robert
AU - Cox, Angela
AU - Southey, Melissa C.
AU - Spurdle, Amanda B.
AU - Gerald, Liesel Fitz
AU - Herkommer, Kathleen
N1 - Publisher Copyright:
© 2015 American Association for Cancer Research.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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 agespecific 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.
AB - 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 agespecific 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.
UR - https://www.scopus.com/pages/publications/84941788242
U2 - 10.1158/1055-9965.EPI-14-0317
DO - 10.1158/1055-9965.EPI-14-0317
M3 - Article
C2 - 25837820
AN - SCOPUS:84941788242
SN - 1055-9965
VL - 24
SP - 1121
EP - 1129
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 7
ER -
SDG 3 Good Health and Well-being