Prostate cancer germline variants with therapeutic implications.

Prostate cancer, the most prevalent noncutaneous cancer and the second leading cause of cancer death among men, is highly heritable. Germline alterations in genes involved in DNA damage repair and the androgen synthesis pathway are associated with worse outcomes. Pathogenic variants in BRCA1, BRCA2, and HSD3B1 are the most prevalent alterations in men with advanced prostate cancer and are associated with increased risk of disease development and progression. These variants are pharmacologically actionable. Poly (ADP-ribose) polymerase (PARP) inhibitors have shown survival benefits in carriers of BRCA1/2 mutations, while HSD3B1 adrenal-permissive carriers might benefit from early intensified androgen blockade treatment. This review explores the impact of pathogenic germline alterations associated with prostate cancer, with a focus on common, clinically actionable variants.