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Polygenic hazard score is associated with prostate cancer in multi-ethnic populations
- Huynh-Le, Minh-Phuong;
- Fan, Chun Chieh;
- Karunamuni, Roshan;
- Thompson, Wesley K;
- Martinez, Maria Elena;
- Eeles, Rosalind A;
- Kote-Jarai, Zsofia;
- Muir, Kenneth;
- Schleutker, Johanna;
- Pashayan, Nora;
- Batra, Jyotsna;
- Grönberg, Henrik;
- Neal, David E;
- Donovan, Jenny L;
- Hamdy, Freddie C;
- Martin, Richard M;
- Nielsen, Sune F;
- Nordestgaard, Børge G;
- Wiklund, Fredrik;
- Tangen, Catherine M;
- Giles, Graham G;
- Wolk, Alicja;
- Albanes, Demetrius;
- Travis, Ruth C;
- Blot, William J;
- Zheng, Wei;
- Sanderson, Maureen;
- Stanford, Janet L;
- Mucci, Lorelei A;
- West, Catharine ML;
- Kibel, Adam S;
- Cussenot, Olivier;
- Berndt, Sonja I;
- Koutros, Stella;
- Sørensen, Karina Dalsgaard;
- Cybulski, Cezary;
- Grindedal, Eli Marie;
- Menegaux, Florence;
- Khaw, Kay-Tee;
- Park, Jong Y;
- Ingles, Sue A;
- Maier, Christiane;
- Hamilton, Robert J;
- Thibodeau, Stephen N;
- Rosenstein, Barry S;
- Lu, Yong-Jie;
- Watya, Stephen;
- Vega, Ana;
- Kogevinas, Manolis;
- Penney, Kathryn L;
- Huff, Chad;
- Teixeira, Manuel R;
- Multigner, Luc;
- Leach, Robin J;
- Cannon-Albright, Lisa;
- Brenner, Hermann;
- John, Esther M;
- Kaneva, Radka;
- Logothetis, Christopher J;
- Neuhausen, Susan L;
- De Ruyck, Kim;
- Pandha, Hardev;
- Razack, Azad;
- Newcomb, Lisa F;
- Fowke, Jay H;
- Gamulin, Marija;
- Usmani, Nawaid;
- Claessens, Frank;
- Gago-Dominguez, Manuela;
- Townsend, Paul A;
- Bush, William S;
- Roobol, Monique J;
- Parent, Marie-Élise;
- Hu, Jennifer J;
- Mills, Ian G;
- Andreassen, Ole A;
- Dale, Anders M;
- Seibert, Tyler M
- et al.
Published Web Location
https://doi.org/10.1038/s41467-021-21287-0Abstract
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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