Polygenic hazard score is associated with prostate cancer in multi-ethnic populations.
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Date
2021-02-23Author
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,
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
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
Humans
Prostatic Neoplasms
Neoplasm Invasiveness
Multivariate Analysis
Multifactorial Inheritance
Aged
Middle Aged
Ethnic Groups
Male
Self Report
Research team
Oncogenetics
Oncogenetics
Language
eng
Date accepted
2021-01-12
License start date
2021-02-23
Citation
Nature communications, 2021, 12 (1), pp. 1236 - ?
Publisher
NATURE PORTFOLIO