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; Graham G 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 FitzGerald; Daniel Leongamornlert; UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology

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, Graham G 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 FitzGerald, Daniel Leongamornlert, UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology

Institut for Klinisk Medicin

48 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Vol/bind	24
Udgave nummer	7
Sider (fra-til)	1121-9
Antal sider	9
ISSN	1055-9965
DOI	https://doi.org/10.1158/1055-9965.epi-14-0317
Status	Udgivet - 1 jul. 2015

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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. P., Ostrander, E. A., Stanford, J. L., Batra, J., Clements, J. A., ... UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology (2015). Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 24(7), 1121-9. https://doi.org/10.1158/1055-9965.epi-14-0317

Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci. / Amin Al Olama, Ali; Benlloch, Sara; Antoniou, Antonis C et al.

I: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Bind 24, Nr. 7, 01.07.2015, s. 1121-9.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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, 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, Y-J, Zhang, H-W, Stephenson, R, Cox, A, Southey, MC, Spurdle, AB, FitzGerald, L, Leongamornlert, D & UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology 2015, 'Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci', Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, bind 24, nr. 7, s. 1121-9. https://doi.org/10.1158/1055-9965.epi-14-0317

Amin Al Olama A, Benlloch S, Antoniou AC, Giles GG, Severi G, Neal DE et al. Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2015 jul. 1;24(7):1121-9. doi: 10.1158/1055-9965.epi-14-0317

Amin Al Olama, Ali ; Benlloch, Sara ; Antoniou, Antonis C et al. / Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci. I: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2015 ; Bind 24, Nr. 7. s. 1121-9.

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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 = "Adult, Aged, Aged, 80 and over, Alleles, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Odds Ratio, Prostatic Neoplasms, Risk Assessment, Risk Factors",

author = "{Amin Al Olama}, Ali and Sara Benlloch and Antoniou, {Antonis C} and Giles, {Graham G} 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 Yong-Jie Lu and Hong-Wei Zhang and Robert Stephenson and Angela Cox and Southey, {Melissa C} and Spurdle, {Amanda B} and Liesel FitzGerald and Daniel Leongamornlert and {UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology}",

note = "{\textcopyright}2015 American Association for Cancer Research.",

year = "2015",

month = jul,

day = "1",

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

language = "English",

volume = "24",

pages = "1121--9",

journal = "Cancer Epidemiology, Biomarkers & Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research (A A C R)",

number = "7",

}

TY - JOUR

T1 - Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci

AU - Amin Al Olama, Ali

AU - Benlloch, Sara

AU - Antoniou, Antonis C

AU - Giles, Graham G

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 - FitzGerald, Liesel

AU - Leongamornlert, Daniel

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

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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alleles

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Odds Ratio

KW - Prostatic Neoplasms

KW - Risk Assessment

KW - Risk Factors

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

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

M3 - Journal article

C2 - 25837820

SN - 1055-9965

VL - 24

SP - 1121

EP - 1129

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & 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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