Genetic Determinants of Aggressive Prostate Cancer in African American Patients

African Americans have 1.7-fold higher incidence, and 2.1-fold higher mortality rates for prostate cancer than Caucasian Americans. Also, African Americans are generally younger at diagnosis, tend to present with more aggressive disease features, and are at a greater risk for metastasis. Inequities in socio-economic status and access to healthcare are large contributors to prostate cancer disparities. However, even after adjusting for the effects of socio-economic factors, racial disparities in prostate cancer incidence and mortality rates remain significant, suggesting a contribution from genetic factors. Dr. Indu Kohaar is using data from a cohort of African American and Caucasian American patients with prostate cancer who have equal access to healthcare and long-term clinical follow-up after initial treatment, to investigate genetic factors that may contribute to prostate cancer racial disparities. Pathogenic and likely pathogenic germline (inherited) variants in known prostate cancer risk genes, as well as a polygenic risk score, will be profiled in the patients in this cohort, to identify any associations with race, age or grade/clinical stage at diagnosis, and patient outcomes. The landscape of tumor mutations in lethal prostate cancer, especially African American patients, will be profiled. Whether there are any associations between germline genetic variants and mutations acquired by tumor cells, and whether such associations impact patients' disease course or clinical outcomes, will be investigated. If successful, this project will lead to the identification of mutational signatures in aggressive prostate cancer genomes, with an emphasis on racial disparities.