Polygenic risk scores (PRS) of common genetic variants have shown promise in prostate cancer risk stratification, but their validity across populations has yet to be confirmed. We evaluated a multiethnic PRS model based on 269 germline genetic risk variants (261 were available for analysis) using an independent population of 13,628 U. S. men. The PRS was strongly associated with prostate cancer, but not with any other disease. Comparing men in the top PRS decile to those at average risk (40%-60%), the odds ratio of prostate cancer was 3.89 (95% confidence interval = 3.24 to 4.68) for men of European ancestry and 3.81 (95% confidence interval = 1.48 to 10.19) for men of African ancestry. By age 85, the cumulative incidence of prostate cancer for European American men was 7.1% in the bottom and 54.1% in the top decile. This suggests that the PRS can be used to identify a substantial proportion of men at high risk for prostate cancer.
Journal of the National Cancer Institute. 2021 Apr 01 [Epub ahead of print]
Anna Plym, Kathryn L Penney, Sarah Kalia, Peter Kraft, David V Conti, Christopher Haiman, Lorelei A Mucci, Adam S Kibel
Urology Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts., Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.