A1 Refereed original research article in a scientific journal
Polygenic hazard score is associated with prostate cancer in multi-ethnic populations
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, 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.; collaborators UKGPCS; APCB (Australian Prostate Cancer BioResource); NC-LA PCaP Investigators; The IMPACT Study Steering Committee and Collaborators; Canary PASS Investigators; The Profile Study Steering Committee; The PRACTICAL Consortium
Publisher: NATURE RESEARCH
Publication year: 2021
Journal: Nature Communications
Journal name in source: NATURE COMMUNICATIONS
Journal acronym: NAT COMMUN
Article number: ARTN 1236
Volume: 12
Issue: 1
Number of pages: 9
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-021-21287-0
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/53697321
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.
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