Genetic risk and likelihood of prostate cancer detection on first biopsy by ancestry.

Despite differences in prostate cancer risk across ancestry groups, relative performance of prostate cancer genetic risks scores (GRS) for positive biopsy prediction in different ancestry groups is unknown. This cross-sectional retrospective analysis examines the association between a polygenic hazard score (PHS290) and risk of prostate cancer diagnosis upon first biopsy in male Veterans using two-sided tests. Our analysis included 36,717 Veterans (10,297 of African ancestry). Unadjusted rates of positive first prostate biopsy increased with higher genetic risk (low risk: 34%, high risk: 58%; p < .001). Among men of African ancestry, higher genetic risk was associated with increased prostate cancer detection on first biopsy (OR 2.18, 95% CI 1.93-2.47), but the effect was stronger among men of European descent (OR 3.89, 95% CI 3.62-4.18). These findings suggest that incorporating genetic risk into prediction models could better personalize biopsy decisions, although further study is needed to achieve equitable genetic risk stratification among ancestry groups.

Journal of the National Cancer Institute. 2024 Jan 11 [Epub ahead of print]

Kyung Min Lee, Tyler Nelson, Alex Bryant, Craig Teerlink, Roman Gulati, Meghana Pagadala, Catherine Tcheandjieu, Kathryn M Pridgen, Scott L DuVall, Kosj Yamoah, Jason L Vassy, Tyler M Seibert, Richard Hauger, Brent S Rose, Julie A Lynch

VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, USA., VA San Diego Healthcare System, San Diego, CA, USA., Department of Radiation Oncology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA., Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Gladstone Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA, USA., James A. Haley Veterans' Hospital, Tampa, FL, USA., Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.