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

Ali Amin Al Olama; Sara Benlloch; Antonis C. Antoniou; Grahamg Giles; Gianluca Severi; David E. Neal; Freddie C. Hamdy; Jenny L. Donovan; Kenneth Muir; Johanna Schleutker; Brian E. Henderson; Christopher A. Haiman; Fredrick R. Schumacher; Nora Pashayan; Paul D P Pharoah; Elaine A. Ostrander; Janet L. Stanford; Jyotsna Batra; Judith A. Clements; Suzanne K. Chambers; Maren Weischer; Børge G. Nordestgaard; Sue A. Ingles; Karina D. Sorensen; Torben F. Orntoft; Jong Y. Park; Cezary Cybulski; Christiane Maier; Thilo Doerk; Joanne L. Dickinson; Lisa Cannon-Albright; Hermann Brenner; Timothy R. Rebbeck; Charnita Zeigler-Johnson; Tomonori Habuchi; Stephen N. Thibodeau; Kathleen A. Cooney; Pierre O. Chappuis; Pierre Hutter; Radka P. Kaneva; William D. Foulkes; Maurice P. Zeegers; Yong Jie Lu; Hong Wei Zhang; Robert Stephenson; Angela Cox; Melissa C. Southey; Amanda B. Spurdle; Liesel Fitz Gerald; Daniel Leongamornlert; Edward Saunders; Malgorzata Tymrakiewicz; Michelle Guy; Tokhir Dadaev; Sarah J. Little; Koveela Govindasami; Emma Sawyer; Rosemary Wilkinson; Kathleen Herkommer; John L. Hopper; Aritaya Lophatonanon; Antje E. Rinckleb; Zsofia Kote-Jarai; Rosalind A. Eeles; Douglas F. Easton; UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology, PRACTICAL Consortium; ProtecT Study Group

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

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

Ali Amin Al Olama^*, Sara Benlloch, Antonis C. Antoniou, Grahamg Giles, Gianluca Severi, David E. Neal, Freddie C. Hamdy, Jenny L. Donovan, Kenneth Muir, Johanna Schleutker, Brian E. Henderson, Christopher A. Haiman, Fredrick R. Schumacher, Nora Pashayan, Paul D P Pharoah, Elaine A. Ostrander, Janet L. Stanford, Jyotsna Batra, Judith A. Clements, Suzanne K. ChambersMaren Weischer, Børge G. Nordestgaard, Sue A. Ingles, Karina D. Sorensen, Torben F. Orntoft, Jong Y. Park, Cezary Cybulski, Christiane Maier, Thilo Doerk, Joanne L. Dickinson, Lisa Cannon-Albright, Hermann Brenner, Timothy R. Rebbeck, Charnita Zeigler-Johnson, Tomonori Habuchi, Stephen N. Thibodeau, Kathleen A. Cooney, Pierre O. Chappuis, Pierre Hutter, Radka P. Kaneva, William D. Foulkes, Maurice P. Zeegers, Yong Jie Lu, Hong Wei Zhang, Robert Stephenson, Angela Cox, Melissa C. Southey, Amanda B. Spurdle, Liesel Fitz Gerald, Daniel Leongamornlert, Edward Saunders, Malgorzata Tymrakiewicz, Michelle Guy, Tokhir Dadaev, Sarah J. Little, Koveela Govindasami, Emma Sawyer, Rosemary Wilkinson, Kathleen Herkommer, John L. Hopper, Aritaya Lophatonanon, Antje E. Rinckleb, Zsofia Kote-Jarai, Rosalind A. Eeles, Douglas F. Easton, UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology, PRACTICAL Consortium, ProtecT Study Group

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

54 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1121-1129
Number of pages	9
Journal	Cancer Epidemiology Biomarkers and Prevention
Volume	24
Issue number	7
DOIs	https://doi.org/10.1158/1055-9965.EPI-14-0317
Publication status	Published - 1 Jul 2015

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10.1158/1055-9965.EPI-14-0317

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Al Olama, A. A., Benlloch, S., Antoniou, A. C., Giles, G., Severi, G., Neal, D. E., Hamdy, F. C., Donovan, J. L., Muir, K., Schleutker, J., Henderson, B. E., Haiman, C. A., Schumacher, F. R., Pashayan, N., Pharoah, P. D. P., Ostrander, E. A., Stanford, J. L., Batra, J., Clements, J. A., ... ProtecT Study Group (2015). Risk analysis of prostate cancer in practical, a multinational consortium, using 25 known prostate cancer susceptibility loci. Cancer Epidemiology Biomarkers and Prevention, 24(7), 1121-1129. https://doi.org/10.1158/1055-9965.EPI-14-0317

@article{7ce0e1e2fe2649d9917ef7ad8611fa8e,

title = "Risk analysis of prostate cancer in practical, a multinational consortium, using 25 known prostate cancer susceptibility loci",

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.",

author = "{Al Olama}, {Ali Amin} and Sara Benlloch and Antoniou, {Antonis C.} and Grahamg Giles and Gianluca Severi and Neal, {David E.} and Hamdy, {Freddie C.} and Donovan, {Jenny L.} and Kenneth Muir and Johanna Schleutker and Henderson, {Brian E.} and Haiman, {Christopher A.} and Schumacher, {Fredrick R.} and Nora Pashayan and Pharoah, {Paul D P} and Ostrander, {Elaine A.} and Stanford, {Janet L.} and Jyotsna Batra and Clements, {Judith A.} and Chambers, {Suzanne K.} and Maren Weischer and Nordestgaard, {B{\o}rge G.} and Ingles, {Sue A.} and Sorensen, {Karina D.} and Orntoft, {Torben F.} and Park, {Jong Y.} and Cezary Cybulski and Christiane Maier and Thilo Doerk and Dickinson, {Joanne L.} and Lisa Cannon-Albright and Hermann Brenner and Rebbeck, {Timothy R.} and Charnita Zeigler-Johnson and Tomonori Habuchi and Thibodeau, {Stephen N.} and Cooney, {Kathleen A.} and Chappuis, {Pierre O.} and Pierre Hutter and Kaneva, {Radka P.} and Foulkes, {William D.} and Zeegers, {Maurice P.} and Lu, {Yong Jie} and Zhang, {Hong Wei} and Robert Stephenson and Angela Cox and Southey, {Melissa C.} and Spurdle, {Amanda B.} and Gerald, {Liesel Fitz} and Daniel Leongamornlert and Edward Saunders and Malgorzata Tymrakiewicz and Michelle Guy and Tokhir Dadaev and Little, {Sarah J.} and Koveela Govindasami and Emma Sawyer and Rosemary Wilkinson and Kathleen Herkommer and Hopper, {John L.} and Aritaya Lophatonanon and Rinckleb, {Antje E.} and Zsofia Kote-Jarai and Eeles, {Rosalind A.} and Easton, {Douglas F.} and David Gillatt and {UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology, PRACTICAL Consortium} and {ProtecT Study Group}",

year = "2015",

month = jul,

day = "1",

doi = "10.1158/1055-9965.EPI-14-0317",

language = "English",

volume = "24",

pages = "1121--1129",

journal = "Cancer Epidemiology Biomarkers and Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research",

number = "7",

}

Al Olama, AA, Benlloch, S, Antoniou, AC, Giles, G, Severi, G, Neal, DE, Hamdy, FC, Donovan, JL, Muir, K, Schleutker, J, Henderson, BE, Haiman, CA, Schumacher, FR, Pashayan, N, Pharoah, PDP, Ostrander, EA, Stanford, JL, Batra, J, Clements, JA, Chambers, SK, Weischer, M, Nordestgaard, BG, Ingles, SA, Sorensen, KD, Orntoft, TF, Park, JY, Cybulski, C, Maier, C, Doerk, T, Dickinson, JL, Cannon-Albright, L, Brenner, H, Rebbeck, TR, Zeigler-Johnson, C, Habuchi, T, Thibodeau, SN, Cooney, KA, Chappuis, PO, Hutter, P, Kaneva, RP, Foulkes, WD, Zeegers, MP, Lu, YJ, Zhang, HW, Stephenson, R, Cox, A, Southey, MC, Spurdle, AB, Gerald, LF, Leongamornlert, D, Saunders, E, Tymrakiewicz, M, Guy, M, Dadaev, T, Little, SJ, Govindasami, K, Sawyer, E, Wilkinson, R, Herkommer, K, Hopper, JL, Lophatonanon, A, Rinckleb, AE, Kote-Jarai, Z, Eeles, RA, Easton, DF, UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology, PRACTICAL Consortium & ProtecT Study Group 2015, 'Risk analysis of prostate cancer in practical, a multinational consortium, using 25 known prostate cancer susceptibility loci', Cancer Epidemiology Biomarkers and Prevention, vol. 24, no. 7, pp. 1121-1129. https://doi.org/10.1158/1055-9965.EPI-14-0317

TY - JOUR

T1 - Risk analysis of prostate cancer in practical, a multinational consortium, using 25 known prostate cancer susceptibility loci

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 - Leongamornlert, Daniel

AU - Saunders, Edward

AU - Tymrakiewicz, Malgorzata

AU - Guy, Michelle

AU - Dadaev, Tokhir

AU - Little, Sarah J.

AU - Govindasami, Koveela

AU - Sawyer, Emma

AU - Wilkinson, Rosemary

AU - Herkommer, Kathleen

AU - Hopper, John L.

AU - Lophatonanon, Aritaya

AU - Rinckleb, Antje E.

AU - Kote-Jarai, Zsofia

AU - Eeles, Rosalind A.

AU - Easton, Douglas F.

AU - Gillatt, David

AU - UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology, PRACTICAL Consortium

AU - ProtecT Study Group

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 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.

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 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.

UR - http://www.scopus.com/inward/record.url?scp=84941788242&partnerID=8YFLogxK

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 -

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

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