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Polygenic hazard score is associated with prostate cancer in multi-ethnic populations
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.
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.
Citations
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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.
Authors
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.
Tangen, C. M.
Giles, G. G.
Wolk, A.
Albanes, D.
Travis, R. C.
Blot, W. J.
Zheng, W.
Sanderson, M.
Stanford, J. L.
Mucci, L. A.
West, Catharine M L
Kibel, A. S.
Cussenot, O.
Berndt, S. I.
Koutros, S.
Sørensen, K. D.
Cybulski, C.
Grindedal, E. M.
Menegaux, F.
Khaw, K. T.
Park, J. Y.
Ingles, S. A.
Maier, C.
Hamilton, R. J.
Thibodeau, S. N.
Rosenstein, B. S.
Lu, Y. J.
Watya, S.
Vega, A.
Kogevinas, M.
Penney, K. L.
Huff, C.
Teixeira, M. R.
Multigner, L.
Leach, R. J.
Cannon-Albright, L.
Brenner, H.
John, E. M.
Kaneva, R.
Logothetis, C. J.
Neuhausen, S. L.
De Ruyck, K.
Pandha, H.
Razack, A.
Newcomb, L. F.
Fowke, J. H.
Gamulin, M.
Usmani, N.
Claessens, F.
Gago-Dominguez, M.
Townsend, Paul A
Bush, W. S.
Roobol, M. J.
Parent, M.
Hu, J. J.
Mills, I. G.
Andreassen, O. A.
Dale, A. M.
Seibert, T. M.
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.
Tangen, C. M.
Giles, G. G.
Wolk, A.
Albanes, D.
Travis, R. C.
Blot, W. J.
Zheng, W.
Sanderson, M.
Stanford, J. L.
Mucci, L. A.
West, Catharine M L
Kibel, A. S.
Cussenot, O.
Berndt, S. I.
Koutros, S.
Sørensen, K. D.
Cybulski, C.
Grindedal, E. M.
Menegaux, F.
Khaw, K. T.
Park, J. Y.
Ingles, S. A.
Maier, C.
Hamilton, R. J.
Thibodeau, S. N.
Rosenstein, B. S.
Lu, Y. J.
Watya, S.
Vega, A.
Kogevinas, M.
Penney, K. L.
Huff, C.
Teixeira, M. R.
Multigner, L.
Leach, R. J.
Cannon-Albright, L.
Brenner, H.
John, E. M.
Kaneva, R.
Logothetis, C. J.
Neuhausen, S. L.
De Ruyck, K.
Pandha, H.
Razack, A.
Newcomb, L. F.
Fowke, J. H.
Gamulin, M.
Usmani, N.
Claessens, F.
Gago-Dominguez, M.
Townsend, Paul A
Bush, W. S.
Roobol, M. J.
Parent, M.
Hu, J. J.
Mills, I. G.
Andreassen, O. A.
Dale, A. M.
Seibert, T. M.
Description
Date
2021
Publisher
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Article
Citation
Huynh-Le MP, Fan CC, Karunamuni R, Thompson WK, Martinez ME, Eeles RA, et al. Polygenic hazard score is associated with prostate cancer in multi-ethnic populations. Nat Commun. 2021;12(1):1236.