Ancestry-Specific DNA Damage Repair Gene Mutations and Prostate Cancer

Prostate cancer (PCa) is a heterogenous malignancy in men, representing the second most diagnosed cancer and the fifth leading cause of cancer-related death globally in 2022. PCa incidence and progression is dependent on several predisposing factors, most significantly genetics and germline/somatic mutations. With the development of whole-genome sequencing (WGS) technology, it is now possible to determine the mutational statuses of PCa-related genes for improved clinical decision making and individualized patient care. The National Comprehensive Cancer Network (NCCN) Guidelines now recommend germline multigene testing followed by post-test genetic counseling. Depending on the germline mutations in homologous recombination (HR) repair genes or in mismatch repair (MMR) genes, specific treatment options, including poly-ADP-ribose polymerase (PARP) inhibition or PD-1 blockade, may be of more clinical benefit. This review highlights specific PCa-related germline mutations in racially diverse populations and therapeutic approaches to treat PCa patients with DNA damage repair gene alterations in advanced disease.