Polygenic hazard score is associated with prostate cancer in multi-ethnic populations
Document Type
Article
Publication Date
2-23-2021
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 >= 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.
Keywords
Genetic models, Cancer, Screening accuracy, Polygenic hazard score (PHS1), Fatal prostate cancer
Divisions
fac_med
Funders
United States National Institute of Health/National Institute of Biomedical Imaging and Bioengineering [Grant No: K08EB026503],United States Department of Defense [Grant No: W81XWH-13-1-0391],University of California [Grant No: CRCCC21CR2060],Research Council of Norway [Grant No: 223273],K.G. Jebsen Stiftelsen,South East Norway Health Authority,National Institute for Health Research Bristol Biomedical Research Centre,UK Department of Health [Grant No: C11043/A4286, C18281/A8145, C18281/A11326, C18281/A15064 & C18281/A24432],Cancer Research UK [Grant No: C18281/A19169]
Publication Title
Nature Communications
Volume
12
Issue
1
Publisher
Nature Portfolio
Publisher Location
HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY