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Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

Original publication

DOI

10.1038/s41588-020-00748-0

Type

Journal article

Journal

Nature genetics

Publication Date

04/01/2021

Volume

53

Pages

65 - 75

Addresses

Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.

Keywords

Humans, Prostatic Neoplasms, Neoplasm Invasiveness, Genetic Predisposition to Disease, Odds Ratio, Risk Factors, Middle Aged, Continental Population Groups, Male, Genome-Wide Association Study, Genetic Loci, Molecular Sequence Annotation