期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-21287-0
关键词
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资金
- United States National Institute of Health/National Institute of Biomedical Imaging and Bioengineering [K08EB026503]
- United States Department of Defense [W81XWH-13-1-0391]
- University of California CRCC [C21CR2060]
- Research Council of Norway [223273]
- K.G. Jebsen Stiftelsen
- South East Norway Health Authority
- National Institute for Health Research Bristol Biomedical Research Centre
- UK Department of Health [C11043/A4286, C18281/A8145, C18281/A11326, C18281/A15064, C18281/A24432]
- Cancer Research UK [C18281/A19169]
The study found that a polygenic hazard score can risk-stratify men for prostate cancer in a multi-ethnic dataset, with significant and effective associations observed across different genetic ancestries.
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.
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