Polygenic hazard score is associated with prostate cancer in multi-ethnic populations

Minh-Phuong Huynh-Le; Chun Chieh Fan; Roshan Karunamuni; Wesley K. Thompson; Maria Elena Martinez; Rosalind A. Eeles; Zsofia Kote-Jarai; Kenneth Muir; Johanna Schleutker; Nora Pashayan; Jyotsna Batra; Henrik Grönberg; David E. Neal; Jenny L. Donovan; Freddie C. Hamdy; Richard M. Martin; Sune F. Nielsen; Børge G. Nordestgaard; Fredrik Wiklund; Catherine M. Tangen; Graham G. Giles; Alicja Wolk; Demetrius Albanes; Ruth C. Travis; William J. Blot; Wei Zheng; Maureen Sanderson; Janet L. Stanford; Lorelei A. Mucci; Catharine M. L. West; Adam S. Kibel; Olivier Cussenot; Sonja I. Berndt; Stella Koutros; Karina Dalsgaard Sørensen; Cezary Cybulski; Eli Marie Grindedal; Florence Menegaux; Kay-Tee Khaw; Jong Y. Park; Sue A. Ingles; Christiane Maier; Robert J. Hamilton; Stephen N. Thibodeau; Barry S. Rosenstein; Yong-Jie Lu; Stephen Watya; Ana Vega; Manolis Kogevinas; Kathryn L. Penney; Chad Huff; Manuel R. Teixeira; Luc Multigner; Robin J. Leach; Lisa Cannon-Albright; Hermann Brenner; Esther M. John; Radka Kaneva; Christopher J. Logothetis; Susan L. Neuhausen; Kim De Ruyck; Hardev Pandha; Azad Razack; Lisa F. Newcomb; Jay H. Fowke; Marija Gamulin; Nawaid Usmani; Frank Claessens; Manuela Gago-Dominguez; Paul A. Townsend; William S. Bush; Monique J. Roobol; Marie-Élise Parent; Jennifer J. Hu; Ian G. Mills; Ole A. Andreassen; Anders M. Dale; Tyler M. Seibert; UKGPCS collaborators; APCB (Australian Prostate Cancer BioResource); NC-LA PCaP Investigators; The IMPACT Study Steering Committee and Collaborators; Canary PASS Investigators; The Profile Study Steering Committee; The PRACTICAL Consortium

doi:10.1038/s41467-021-21287-0

Polygenic hazard score is associated with prostate cancer in multi-ethnic populations

Minh-Phuong Huynh-Le, Chun Chieh Fan, Roshan Karunamuni, Wesley K. Thompson, Maria Elena Martinez, Rosalind A. Eeles, Zsofia Kote-Jarai, Kenneth Muir, Johanna Schleutker, Nora Pashayan, Jyotsna Batra, Henrik Grönberg, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Sune F. Nielsen, Børge G. Nordestgaard, Fredrik Wiklund, Catherine M. TangenGraham G. Giles, Alicja Wolk, Demetrius Albanes, Ruth C. Travis, William J. Blot, Wei Zheng, Maureen Sanderson, Janet L. Stanford, Lorelei A. Mucci, Catharine M. L. West, Adam S. Kibel, Olivier Cussenot, Sonja I. Berndt, Stella Koutros, Karina Dalsgaard Sørensen, Cezary Cybulski, Eli Marie Grindedal, Florence Menegaux, Kay-Tee Khaw, Jong Y. Park, Sue A. Ingles, Christiane Maier, Robert J. Hamilton, Stephen N. Thibodeau, Barry S. Rosenstein, Yong-Jie Lu, Stephen Watya, Ana Vega, Manolis Kogevinas, Kathryn L. Penney, Chad Huff, Manuel R. Teixeira, Luc Multigner, Robin J. Leach, Lisa Cannon-Albright, Hermann Brenner, Esther M. John, Radka Kaneva, Christopher J. Logothetis, Susan L. Neuhausen, Kim De Ruyck, Hardev Pandha, Azad Razack, Lisa F. Newcomb, Jay H. Fowke, Marija Gamulin, Nawaid Usmani, Frank Claessens, Manuela Gago-Dominguez, Paul A. Townsend, William S. Bush, Monique J. Roobol, Marie-Élise Parent, Jennifer J. Hu, Ian G. Mills, Ole A. Andreassen, Anders M. Dale, Tyler M. Seibert, UKGPCS collaborators, APCB (Australian Prostate Cancer BioResource), NC-LA PCaP Investigators, The IMPACT Study Steering Committee and Collaborators, Canary PASS Investigators, The Profile Study Steering Committee, The PRACTICAL Consortium

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Abstract

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10−180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

Original language	English
Article number	1236
Number of pages	9
Journal	Nature Communications
Volume	12
DOIs	https://doi.org/10.1038/s41467-021-21287-0
Publication status	Published - 23 Feb 2021

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Polygenic hazard score is associated with prostate cancer in multi-ethnic populations
Copyright 2021 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 1.1 MBLicence: CC BY

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Huynh-Le, M.-P., Fan, C. C., Karunamuni, R., Thompson, W. K., Martinez, M. E., Eeles, R. A., Kote-Jarai, Z., Muir, K., Schleutker, J., Pashayan, N., Batra, J., Grönberg, H., Neal, D. E., Donovan, J. L., Hamdy, F. C., Martin, R. M., Nielsen, S. F., Nordestgaard, B. G., Wiklund, F., ... Consortium, T. PRACTICAL. (2021). Polygenic hazard score is associated with prostate cancer in multi-ethnic populations. Nature Communications, 12, Article 1236. https://doi.org/10.1038/s41467-021-21287-0

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title = "Polygenic hazard score is associated with prostate cancer in multi-ethnic populations",

abstract = "Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10−180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.",

author = "Minh-Phuong Huynh-Le and Fan, {Chun Chieh} and Roshan Karunamuni and Thompson, {Wesley K.} and Martinez, {Maria Elena} and Eeles, {Rosalind A.} and Zsofia Kote-Jarai and Kenneth Muir and Johanna Schleutker and Nora Pashayan and Jyotsna Batra and Henrik Gr{\"o}nberg and Neal, {David E.} and Donovan, {Jenny L.} and Hamdy, {Freddie C.} and Martin, {Richard M.} and Nielsen, {Sune F.} and Nordestgaard, {B{\o}rge G.} and Fredrik Wiklund and Tangen, {Catherine M.} and Giles, {Graham G.} and Alicja Wolk and Demetrius Albanes and Travis, {Ruth C.} and Blot, {William J.} and Wei Zheng and Maureen Sanderson and Stanford, {Janet L.} and Mucci, {Lorelei A.} and West, {Catharine M. L.} and Kibel, {Adam S.} and Olivier Cussenot and Berndt, {Sonja I.} and Stella Koutros and S{\o}rensen, {Karina Dalsgaard} and Cezary Cybulski and Grindedal, {Eli Marie} and Florence Menegaux and Kay-Tee Khaw and Park, {Jong Y.} and Ingles, {Sue A.} and Christiane Maier and Hamilton, {Robert J.} and Thibodeau, {Stephen N.} and Rosenstein, {Barry S.} and Yong-Jie Lu and Stephen Watya and Ana Vega and Manolis Kogevinas and Penney, {Kathryn L.} and Chad Huff and Teixeira, {Manuel R.} and Luc Multigner and Leach, {Robin J.} and Lisa Cannon-Albright and Hermann Brenner and John, {Esther M.} and Radka Kaneva and Logothetis, {Christopher J.} and Neuhausen, {Susan L.} and {De Ruyck}, Kim and Hardev Pandha and Azad Razack and Newcomb, {Lisa F.} and Fowke, {Jay H.} and Marija Gamulin and Nawaid Usmani and Frank Claessens and Manuela Gago-Dominguez and Townsend, {Paul A.} and Bush, {William S.} and Roobol, {Monique J.} and Marie-{\'E}lise Parent and Hu, {Jennifer J.} and Mills, {Ian G.} and Andreassen, {Ole A.} and Dale, {Anders M.} and Seibert, {Tyler M.} and UKGPCS collaborators and BioResource), {APCB (Australian Prostate Cancer} and Investigators, {NC-LA PCaP} and Collaborators, {The IMPACT Study Steering Committee and} and Investigators, {Canary PASS} and Committee, {The Profile Study Steering} and Consortium, {The PRACTICAL}",

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doi = "10.1038/s41467-021-21287-0",

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Huynh-Le, M-P, Fan, CC, Karunamuni, R, Thompson, WK, Martinez, ME, Eeles, RA, Kote-Jarai, Z, Muir, K, Schleutker, J, Pashayan, N, Batra, J, Grönberg, H, Neal, DE, Donovan, JL, Hamdy, FC, Martin, RM, Nielsen, SF, Nordestgaard, BG, Wiklund, F, Tangen, CM, Giles, GG, Wolk, A, Albanes, D, Travis, RC, Blot, WJ, Zheng, W, Sanderson, M, Stanford, JL, Mucci, LA, West, CML, Kibel, AS, Cussenot, O, Berndt, SI, Koutros, S, Sørensen, KD, Cybulski, C, Grindedal, EM, Menegaux, F, Khaw, K-T, Park, JY, Ingles, SA, Maier, C, Hamilton, RJ, Thibodeau, SN, Rosenstein, BS, Lu, Y-J, Watya, S, Vega, A, Kogevinas, M, Penney, KL, Huff, C, Teixeira, MR, Multigner, L, Leach, RJ, Cannon-Albright, L, Brenner, H, John, EM, Kaneva, R, Logothetis, CJ, Neuhausen, SL, De Ruyck, K, Pandha, H, Razack, A, Newcomb, LF, Fowke, JH, Gamulin, M, Usmani, N, Claessens, F, Gago-Dominguez, M, Townsend, PA, Bush, WS, Roobol, MJ, Parent, M-É, Hu, JJ, Mills, IG, Andreassen, OA, Dale, AM, Seibert, TM, collaborators, UKGPCS, BioResource), APCB, Investigators, NC-LAPC, Collaborators, TIMPACTSSCA, Investigators, CPASS, Committee, TPSS & Consortium, TPRACTICAL 2021, 'Polygenic hazard score is associated with prostate cancer in multi-ethnic populations', Nature Communications, vol. 12, 1236. https://doi.org/10.1038/s41467-021-21287-0

TY - JOUR

T1 - Polygenic hazard score is associated with prostate cancer in multi-ethnic populations

AU - Huynh-Le, Minh-Phuong

AU - Fan, Chun Chieh

AU - Karunamuni, Roshan

AU - Thompson, Wesley K.

AU - Martinez, Maria Elena

AU - Eeles, Rosalind A.

AU - Kote-Jarai, Zsofia

AU - Muir, Kenneth

AU - Schleutker, Johanna

AU - Pashayan, Nora

AU - Batra, Jyotsna

AU - Grönberg, Henrik

AU - Neal, David E.

AU - Donovan, Jenny L.

AU - Hamdy, Freddie C.

AU - Martin, Richard M.

AU - Nielsen, Sune F.

AU - Nordestgaard, Børge G.

AU - Wiklund, Fredrik

AU - Tangen, Catherine M.

AU - Giles, Graham G.

AU - Wolk, Alicja

AU - Albanes, Demetrius

AU - Travis, Ruth C.

AU - Blot, William J.

AU - Zheng, Wei

AU - Sanderson, Maureen

AU - Stanford, Janet L.

AU - Mucci, Lorelei A.

AU - West, Catharine M. L.

AU - Kibel, Adam S.

AU - Cussenot, Olivier

AU - Berndt, Sonja I.

AU - Koutros, Stella

AU - Sørensen, Karina Dalsgaard

AU - Cybulski, Cezary

AU - Grindedal, Eli Marie

AU - Menegaux, Florence

AU - Khaw, Kay-Tee

AU - Park, Jong Y.

AU - Ingles, Sue A.

AU - Maier, Christiane

AU - Hamilton, Robert J.

AU - Thibodeau, Stephen N.

AU - Rosenstein, Barry S.

AU - Lu, Yong-Jie

AU - Watya, Stephen

AU - Vega, Ana

AU - Kogevinas, Manolis

AU - Penney, Kathryn L.

AU - Huff, Chad

AU - Teixeira, Manuel R.

AU - Multigner, Luc

AU - Leach, Robin J.

AU - Cannon-Albright, Lisa

AU - Brenner, Hermann

AU - John, Esther M.

AU - Kaneva, Radka

AU - Logothetis, Christopher J.

AU - Neuhausen, Susan L.

AU - De Ruyck, Kim

AU - Pandha, Hardev

AU - Razack, Azad

AU - Newcomb, Lisa F.

AU - Fowke, Jay H.

AU - Gamulin, Marija

AU - Usmani, Nawaid

AU - Claessens, Frank

AU - Gago-Dominguez, Manuela

AU - Townsend, Paul A.

AU - Bush, William S.

AU - Roobol, Monique J.

AU - Parent, Marie-Élise

AU - Hu, Jennifer J.

AU - Mills, Ian G.

AU - Andreassen, Ole A.

AU - Dale, Anders M.

AU - Seibert, Tyler M.

AU - collaborators, UKGPCS

AU - BioResource), APCB (Australian Prostate Cancer

AU - Investigators, NC-LA PCaP

AU - Collaborators, The IMPACT Study Steering Committee and

AU - Investigators, Canary PASS

AU - Committee, The Profile Study Steering

AU - Consortium, The PRACTICAL

PY - 2021/2/23

Y1 - 2021/2/23

N2 - Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10−180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

AB - Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10−180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

U2 - 10.1038/s41467-021-21287-0

DO - 10.1038/s41467-021-21287-0

M3 - Article

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

M1 - 1236

ER -

Polygenic hazard score is associated with prostate cancer in multi-ethnic populations

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