Polygenic hazard score is associated with prostate cancer in multi-ethnic populations.
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ICR Authors
Authors
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
UKGPCS collaborators,
APCB (Australian Prostate Cancer BioResource),
NC-LA PCaP Investigators,
IMPACT Study Steering Committee and Collaborators,
Canary PASS Investigators,
Profile Study Steering Committee,
PRACTICAL Consortium,
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
UKGPCS collaborators,
APCB (Australian Prostate Cancer BioResource),
NC-LA PCaP Investigators,
IMPACT Study Steering Committee and Collaborators,
Canary PASS Investigators,
Profile Study Steering Committee,
PRACTICAL Consortium,
Document Type
Journal Article
Date
2021-02-23
Date Accepted
2021-01-12
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.
Citation
Nature communications, 2021, 12 (1), pp. 1236 - ?
Source Title
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
Research Team
Oncogenetics
Oncogenetics
Oncogenetics