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

Huynh-Le, Minh-Phuong; Fan, Chun Chieh; Karunamuni, Roshan; Thompson, Wesley K; Martinez, Maria Elena; Eeles, Rosalind A; Kote-Jarai, Zsofia; Muir, Kenneth et al. · Nat Commun · 2021

case_control · Level III

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Abstract

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS<sub>1</sub>) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS<sub>2</sub> (PHS<sub>1</sub>, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS<sub>2</sub> 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<sup>-180</sup>). Comparing the 80<sup>th</sup>/20<sup>th</sup> PHS<sub>2</sub> 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<sub>2</sub> risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

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