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

Huynh-Le, Minh Phuong; Kogevinas, Manolis; PRACTICAL Consortium

doi:http://dx.doi.org/10.1038/s41467-021-21287-0

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

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Huynh-Le MP, Fan CC, Karunamuni R, Thompson WK, Martinez ME, Eeles RA et al. Polygenic hazard score is associated with prostate cancer in multi-ethnic populations. Nat Commun. 2021;12(1):1236. DOI: 10.1038/s41467-021-21287-0

Abstract

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.