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

A. Amin al Olama; S. Benlloch; A.C. Antoniou; G.G. Giles; G. Severi; D.E. Neal; F.C. Hamdy; J.L. Donovan; K. Muir; J. Schleutker; B.E. Henderson; C.A. Haiman; F.R. Schumacher; N. Pashayan; P.D. Pharoah; E.A. Ostrander; J.L. Stanford; J. Batra; J.A. Clements; S.K. Chambers; M. Weischer; B. G. Nordestgaard; S.A. Ingles; K.D. Sorensen; T.F. Orntoft; J.Y. Park; C. Cybulski; C. Maier; T. Doerk; J.L. Dickinson; L. Cannon-Albright; H. Brenner; T.R. Rebbeck; C. Zeigler-Johnson; T. Habuchi; S.N. Thibodeau; K.A. Cooney; P.O. Chappuis; P. Hutter; R.P. Kaneva; W.D. Foulkes; M.P. Zeegers; Y.J. Lu; H.W. Zhang; R. Stephenson; A. Cox; M.C. Southey; A.B. Spurdle; L. FitzGerald; D. Leongamornlert; E. Saunders; M. Tymrakiewicz; M. Guy; T. Dadaev; S.J. Little; K. Govindasami; E. Sawyer; R. Wilkinson; K. Herkommer; J.L. Hopper; A. Lophatonanon; A.E. Rinckleb; Z. Kote-Jarai; R.A. Eeles; D.F. Easton

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

A. Amin al Olama^*, S. Benlloch, A.C. Antoniou, G.G. Giles, G. Severi, D.E. Neal, F.C. Hamdy, J.L. Donovan, K. Muir, J. Schleutker, B.E. Henderson, C.A. Haiman, F.R. Schumacher, N. Pashayan, P.D. Pharoah, E.A. Ostrander, J.L. Stanford, J. Batra, J.A. Clements, S.K. ChambersM. Weischer, B. G. Nordestgaard, S.A. Ingles, K.D. Sorensen, T.F. Orntoft, J.Y. Park, C. Cybulski, C. Maier, T. Doerk, J.L. Dickinson, L. Cannon-Albright, H. Brenner, T.R. Rebbeck, C. Zeigler-Johnson, T. Habuchi, S.N. Thibodeau, K.A. Cooney, P.O. Chappuis, P. Hutter, R.P. Kaneva, W.D. Foulkes, M.P. Zeegers, Y.J. Lu, H.W. Zhang, R. Stephenson, A. Cox, M.C. Southey, A.B. Spurdle, L. FitzGerald, D. Leongamornlert, E. Saunders, M. Tymrakiewicz, M. Guy, T. Dadaev, S.J. Little, K. Govindasami, E. Sawyer, R. Wilkinson, K. Herkommer, J.L. Hopper, A. Lophatonanon, A.E. Rinckleb, Z. Kote-Jarai, R.A. Eeles, D.F. Easton

^*Corresponding author for this work

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

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 & Prevention
Volume	24
Issue number	7
DOIs	https://doi.org/10.1158/1055-9965.EPI-14-0317
Publication status	Published - Jul 2015

Keywords

GENOME-WIDE ASSOCIATION
BREAST-CANCER
MULTIPLE LOCI
PREDICTION
VARIANTS
IDENTIFICATION
BRCA2

Access to Document

10.1158/1055-9965.EPI-14-0317

Cite this

Amin al Olama, A., Benlloch, S., Antoniou, A. C., Giles, G. 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., Ostrander, E. A., Stanford, J. L., Batra, J., Clements, J. A., ... Easton, D. F. (2015). Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci. Cancer Epidemiology Biomarkers & Prevention, 24(7), 1121-1129. https://doi.org/10.1158/1055-9965.EPI-14-0317

@article{1889db46b3bc474694f95f34e48ec322,

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.",

keywords = "GENOME-WIDE ASSOCIATION, BREAST-CANCER, MULTIPLE LOCI, PREDICTION, VARIANTS, IDENTIFICATION, BRCA2",

author = "{Amin al Olama}, A. and S. Benlloch and A.C. Antoniou and G.G. Giles and G. Severi and D.E. Neal and F.C. Hamdy and J.L. Donovan and K. Muir and J. Schleutker and B.E. Henderson and C.A. Haiman and F.R. Schumacher and N. Pashayan and P.D. Pharoah and E.A. Ostrander and J.L. Stanford and J. Batra and J.A. Clements and S.K. Chambers and M. Weischer and Nordestgaard, {B. G.} and S.A. Ingles and K.D. Sorensen and T.F. Orntoft and J.Y. Park and C. Cybulski and C. Maier and T. Doerk and J.L. Dickinson and L. Cannon-Albright and H. Brenner and T.R. Rebbeck and C. Zeigler-Johnson and T. Habuchi and S.N. Thibodeau and K.A. Cooney and P.O. Chappuis and P. Hutter and R.P. Kaneva and W.D. Foulkes and M.P. Zeegers and Y.J. Lu and H.W. Zhang and R. Stephenson and A. Cox and M.C. Southey and A.B. Spurdle and L. FitzGerald and D. Leongamornlert and E. Saunders and M. Tymrakiewicz and M. Guy and T. Dadaev and S.J. Little and K. Govindasami and E. Sawyer and R. Wilkinson and K. Herkommer and J.L. Hopper and A. Lophatonanon and A.E. Rinckleb and Z. Kote-Jarai and R.A. Eeles and D.F. Easton",

year = "2015",

month = jul,

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

language = "English",

volume = "24",

pages = "1121--1129",

journal = "Cancer Epidemiology Biomarkers & Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

number = "7",

}

Amin al Olama, A, Benlloch, S, Antoniou, AC, Giles, GG, Severi, G, Neal, DE, Hamdy, FC, Donovan, JL, Muir, K, Schleutker, J, Henderson, BE, Haiman, CA, Schumacher, FR, Pashayan, N, Pharoah, PD, 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, FitzGerald, L, 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 2015, 'Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci', Cancer Epidemiology Biomarkers & 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 - Amin al Olama, A.

AU - Benlloch, S.

AU - Antoniou, A.C.

AU - Giles, G.G.

AU - Severi, G.

AU - Neal, D.E.

AU - Hamdy, F.C.

AU - Donovan, J.L.

AU - Muir, K.

AU - Schleutker, J.

AU - Henderson, B.E.

AU - Haiman, C.A.

AU - Schumacher, F.R.

AU - Pashayan, N.

AU - Pharoah, P.D.

AU - Ostrander, E.A.

AU - Stanford, J.L.

AU - Batra, J.

AU - Clements, J.A.

AU - Chambers, S.K.

AU - Weischer, M.

AU - Nordestgaard, B. G.

AU - Ingles, S.A.

AU - Sorensen, K.D.

AU - Orntoft, T.F.

AU - Park, J.Y.

AU - Cybulski, C.

AU - Maier, C.

AU - Doerk, T.

AU - Dickinson, J.L.

AU - Cannon-Albright, L.

AU - Brenner, H.

AU - Rebbeck, T.R.

AU - Zeigler-Johnson, C.

AU - Habuchi, T.

AU - Thibodeau, S.N.

AU - Cooney, K.A.

AU - Chappuis, P.O.

AU - Hutter, P.

AU - Kaneva, R.P.

AU - Foulkes, W.D.

AU - Zeegers, M.P.

AU - Lu, Y.J.

AU - Zhang, H.W.

AU - Stephenson, R.

AU - Cox, A.

AU - Southey, M.C.

AU - Spurdle, A.B.

AU - FitzGerald, L.

AU - Leongamornlert, D.

AU - Saunders, E.

AU - Tymrakiewicz, M.

AU - Guy, M.

AU - Dadaev, T.

AU - Little, S.J.

AU - Govindasami, K.

AU - Sawyer, E.

AU - Wilkinson, R.

AU - Herkommer, K.

AU - Hopper, J.L.

AU - Lophatonanon, A.

AU - Rinckleb, A.E.

AU - Kote-Jarai, Z.

AU - Eeles, R.A.

AU - Easton, D.F.

PY - 2015/7

Y1 - 2015/7

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.

KW - GENOME-WIDE ASSOCIATION

KW - BREAST-CANCER

KW - MULTIPLE LOCI

KW - PREDICTION

KW - VARIANTS

KW - IDENTIFICATION

KW - BRCA2

U2 - 10.1158/1055-9965.EPI-14-0317

DO - 10.1158/1055-9965.EPI-14-0317

M3 - Article

SN - 1055-9965

VL - 24

SP - 1121

EP - 1129

JO - Cancer Epidemiology Biomarkers & Prevention

JF - Cancer Epidemiology Biomarkers & Prevention

IS - 7

ER -