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

Huynh-Le, Minh-Phuong and Fan, Chun Chieh and Karunamuni, Roshan and Thompson, Wesley K. and Martinez, Maria Elena and Eeles, Rosalind A. and Kote-Jarai, Zsofia and Muir, Kenneth and Schleutker, Johanna and Pashayan, Nora and Batra, Jyotsna and Gronberg, Henrik and Neal, David E. and Donovan, Jenny L. and Hamdy, Freddie C. and Martin, Richard M. and Nielsen, Sune F. and Nordestgaard, Borge G. and Wiklund, Fredrik and Tangen, Catherine M. and Giles, Graham G. and Wolk, Alicja and Albanes, Demetrius and Travis, Ruth C. and Blot, William J. and Zheng, Wei and Sanderson, Maureen and Stanford, Janet L. and Mucci, Lorelei A. and West, Catharine M. L. and Kibel, Adam S. and Cussenot, Olivier and Berndt, Sonja I. and Koutros, Stella and Sorensen, Karina Dalsgaard and Cybulski, Cezary and Grindedal, Eli Marie and Menegaux, Florence and Khaw, Kay-Tee and Park, Jong Y. and Ingles, Sue A. and Maier, Christiane and Hamilton, Robert J. and Thibodeau, Stephen N. and Rosenstein, Barry S. and Lu, Yong-Jie and Watya, Stephen and Vega, Ana and Kogevinas, Manolis and Penney, Kathryn L. and Huff, Chad and Teixeira, Manuel R. and Multigner, Luc and Leach, Robin J. and Cannon-Albright, Lisa and Brenner, Hermann and John, Esther M. and Kaneva, Radka and Logothetis, Christopher J. and Neuhausen, Susan L. and De Ruyck, Kim and Pandha, Hardev and Razack, Azad and Newcomb, Lisa F. and Fowke, Jay H. and Gamulin, Marija and Usmani, Nawaid and Claessens, Frank and Gago-Dominguez, Manuela and Townsend, Paul A. and Bush, William S. and Roobol, Monique J. and Parent, Marie-Elise and Hu, Jennifer J. and Mills, Ian G. and Andreassen, Ole A. and Dale, Anders M. and Seibert, Tyler M. and UKGPCS collaborators, - and Bio, APCB Australian Prostate Canc and Investigators, NC-LA PCaP and Col, IMPACT Study Steering Comm and Investigators, Canary PASS and Comm, Profile Study Steering and Consortium, PRACTICAL (2021) Polygenic hazard score is associated with prostate cancer in multi-ethnic populations. Nature Communications, 12 (1). ISSN 2041-1723, DOI https://doi.org/10.1038/s41467-021-21287-0.

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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 >= 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.

Item Type: Article
Funders: United States National Institute of Health/National Institute of Biomedical Imaging and Bioengineering [Grant No: K08EB026503], United States Department of Defense [Grant No: W81XWH-13-1-0391], University of California [Grant No: CRCCC21CR2060], Research Council of Norway [Grant No: 223273], K.G. Jebsen Stiftelsen, South East Norway Health Authority, National Institute for Health Research Bristol Biomedical Research Centre, UK Department of Health [Grant No: C11043/A4286, C18281/A8145, C18281/A11326, C18281/A15064 & C18281/A24432], Cancer Research UK [Grant No: C18281/A19169]
Uncontrolled Keywords: Genetic models; Cancer; Screening accuracy; Polygenic hazard score (PHS1); Fatal prostate cancer
Subjects: Q Science > Q Science (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Medicine
Depositing User: Ms Zaharah Ramly
Date Deposited: 14 Sep 2022 02:49
Last Modified: 14 Sep 2022 02:49
URI: http://eprints.um.edu.my/id/eprint/34695

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