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PHS Monday Seminar: Burcu Darst, PhD: “Genetic risk of prostate cancer across men from multi-ancestry populations”

April 19, 2021 @ 12:00 pm - 1:00 pm

Postdoctoral Scholar

Center for Genetic Epidemiology

Keck School of Medicine

University of Southern California

Abstract

Prostate cancer represents one of the largest health disparities in the US, with men of African ancestry having the highest incidence and mortality rates. While the causes of this disparity have been largely unknown, recent evidence suggests that germline genetics is a contributing factor. Our recent research aims to better understand the underlying genetic contributions to prostate cancer and prostate cancer health disparities. In the largest and most diverse prostate cancer genome-wide association study (GWAS) to date, we identified novel genetic variants that contribute to risk of prostate cancer and we developed a multi-ancestry polygenic risk score (PRS) that was highly predictive of risk across diverse populations. In whole-exome sequencing investigations, we have also identified rare variants that contribute to distinguish between risk of aggressive and non-aggressive prostate cancer and found that combining the multi-ancestry PRS with carrier status could substantially improve risk estimates. Further, to understand the biological mechanisms impacted by genetic risk of PCa, we conducted integrative analyses of the multi-ancestry PRS and serum metabolomics in African ancestry men and observed evidence of the PRS impacting levels of particular metabolite. These findings support the role of germline variation contributing to health disparities in PCa risk, with the PRS offering an approach for personalized risk prediction across populations and informing the biological mechanisms underlying PCa risk.

Details

Date:
April 19, 2021
Time:
12:00 pm - 1:00 pm
Event Category: