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

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS(1)) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS(2)...

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Detalles Bibliográficos
Autores principales: 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 M. L., 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902617/
https://www.ncbi.nlm.nih.gov/pubmed/33623038
http://dx.doi.org/10.1038/s41467-021-21287-0
Descripción
Sumario:Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS(1)) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS(2) (PHS(1), adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS(2) 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 80(th)/20(th) PHS(2) 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. PHS(2) risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

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