Ancestry-Specific DNA Damage Repair Gene Mutations and Prostate Cancer

This review is intended to reflect the currently available literature on both clinically significant germline mutations in DNA damage repair (DDR) genes as well as the importance of ancestral diversity in the pathogenesis of prostate cancer (PCa). The second most prevalent cancer worldwide in men is PCa, causing significant morbidity and mortality in its advanced stage. Emerging data highlight the substantial role of germline mutations of DDR genes in PCa pathogenesis, especially in progression to aggressive forms of the disease. Germline genetic testing is recognized as a necessary tool for efficient, individualized patient care. NCCR guidelines recommend inquiring about the family history of PCa and known germline variants and, if indicated, proceeding with germline multigene testing followed by post-test genetic counseling. Depending on the germline mutations in HR repair genes or in MMR genes, specific treatment options may provide clinical benefit. We will discuss specific germline mutations that are involved in PCa progression and prognosis in racially diverse populations.