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

• Main Authors: 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, Gronberg, Henrik, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nielsen, Sune F., Nordestgaard, Borge 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, Sorensen, 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-Elise, Hu, Jennifer J., Mills, Ian G., Andreassen, Ole A., Dale, Anders M., Seibert, Tyler M., UKGPCS collaborators, -, Bio, APCB Australian Prostate Canc, Investigators, NC-LA PCaP, Col, IMPACT Study Steering Comm, Investigators, Canary PASS, Comm, Profile Study Steering, Consortium, PRACTICAL
• Format: Article
• Published: Nature Portfolio 2021
• Subjects: Q Science (General); RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Online Access: http://eprints.um.edu.my/34695/

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 >= 10ng/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) 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. A polygenic hazard score (PHS1) improves prostate cancer screening accuracy in European patients. Here, the authors test the performance of a version compatible with OncoArray genotypes (PHS2) in a multi-ethnic dataset and find that it risk-stratifies men for any, aggressive, and fatal prostate cancer.