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

Title: 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 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; UKGPCS collaborators; APCB (Australian Prostate Cancer BioResource); NC-LA PCaP Investigators; IMPACT Study Steering Committee and Collaborators; Canary PASS Investigators; Profile Study Steering Committee; PRACTICAL Consortium
Publisher Information: Springer Nature; //doi.org/10.1038/s41467-021-21287-0
Publication Year: 2021
Collection: Apollo - University of Cambridge Repository
Subject Terms: Aged; Ethnicity; Humans; Male; Middle Aged; Multifactorial Inheritance; Multivariate Analysis; Neoplasm Invasiveness; Prostatic Neoplasms; Self Report
Description: 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.
Document Type: article in journal/newspaper
File Description: application/pdf; text/xml; application/zip
Language: English
Relation: 21287; https://www.repository.cam.ac.uk/handle/1810/318029
DOI: 10.17863/CAM.65144
Availability: https://www.repository.cam.ac.uk/handle/1810/318029; https://doi.org/10.17863/CAM.65144
Rights: Attribution 4.0 International (CC BY 4.0) ; https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.68076210
Database: BASE