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

MP Huynh-Le, CC Fan, R Karunamuni, WK Thompson, M E Martinez, RA Eeles, Z Kote-Jarai, K Muir, J Schleutker, N Pashayan, J Batra, H Grönberg, DE Neal, JL Donovan, FC Hamdy, RM Martin, SF Nielsen, BG Nordestgaard, F Wiklund, C M TangenGG Giles, A Wolk, D Albanes, RC Travis, WJ Blot, W Zheng, M Sanderson, J L Stanford, LA Mucci, CML West, AS Kibel, O Cussenot, SI Berndt, S Koutros, KD Sørensen, C Cybulski, EM Grindedal, F Menegaux, KTH Khaw, JY Park, SA Ingles, C Maier, RJ Hamilton, SN Thibodeau, B S Rosenstein, YJ Lu, S Watya, A Vega, M Kogevinas, KL Penney, C Huff, MR Teixeira, L Multigner, RJ Leach, L Cannon-Albright, H Brenner, EM John, R Kaneva, CJ Logothetis, SL Neuhausen, K De Ruyck, H Pandha, A Razack, LF Newcomb, JH Fowke, M Gamulin, N Usmani, F Claessens, M Gago-Dominguez, PA Townsend, WS Bush, Monique Roobol - Bouts, MÉ Parent, JJ Hu, IG Mills, OA Andreassen, AM Dale, TM Seibert

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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 languageEnglish
Article number1236
JournalNature Communications
Issue number1
Publication statusPublished - 23 Feb 2021

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