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

Minh-Phuong Huynh-Le (1) , Chun Chieh Fan (1) , Roshan Karunamuni (1) , Wesley Thompson (1) , Maria Elena Martinez (1) , Rosalind Eeles (2) , Zsofia Kote-Jarai (2) , Kenneth Muir (3) , Johanna Schleutker (4) , Nora Pashayan (5, 6) , Jyotsna Batra , Henrik Grönberg , David Neal , Jenny Donovan , Freddie Hamdy , Richard Martin , Sune Nielsen , Børge Nordestgaard , Fredrik Wiklund , Catherine Tangen , Graham Giles , Alicja Wolk , Demetrius Albanes , Ruth Travis , William Blot , Wei Zheng , Maureen Sanderson , Janet Stanford , Lorelei Mucci , Catharine West , Adam Kibel , Olivier Cussenot (7) , Sonja Berndt , Stella Koutros , Karina Dalsgaard Sørensen , Cezary Cybulski , Eli Marie Grindedal , Florence Menegaux (8) , Kay-Tee Khaw , Jong Park , Sue Ingles , Christiane Maier , Robert Hamilton , Stephen Thibodeau , Barry Rosenstein , Yong-Jie Lu , Stephen Watya , Ana Vega , Manolis Kogevinas , Kathryn Penney , Chad Huff , Manuel Teixeira , Luc Multigner (9) , Robin Leach , Lisa Cannon-Albright , Hermann Brenner , Esther John , Radka Kaneva , Christopher Logothetis , Susan Neuhausen , Kim de Ruyck , Hardev Pandha , Azad Razack , Lisa Newcomb , Jay Fowke , Marija Gamulin , Nawaid Usmani , Frank Claessens , Manuela Gago-Dominguez , Paul Townsend , William Bush , Monique Roobol , Marie-Élise Parent , Jennifer Hu , Ian Mills , Ole Andreassen , Anders Dale (1) , Tyler Seibert (1)

1 UC San Diego - University of California [San Diego]
2 The institute of cancer research [London]
3 University of Manchester [Manchester]
4 University of Turku
5 Centre for Cancer Genetic Epidemiology [Cambridge]
6 UCL - University College of London [London]
7 CeRePP - Centre de Recherche pour les Pathologies Prostatiques [Paris]
8 CESP - Centre de recherche en épidémiologie et santé des populations
9 Irset - Institut de recherche en santé, environnement et travail

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS (PHS, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS 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). Comparing the 80/20 PHS 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 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

Keywords: Biomarkers; Medical research; Oncology

Domains: Life Sciences [q-bio]; Cancer

Minh-Phuong Huynh-Le, Chun Chieh Fan, Roshan Karunamuni, Wesley Thompson, Maria Elena Martinez, et al.. Polygenic hazard score is associated with prostate cancer in multi-ethnic populations. Nature Communications, 2021, 12 (1), pp.1236. ⟨10.1038/s41467-021-21287-0⟩. ⟨hal-03281257⟩