Germline Mutations and Ancestry in Prostate Cancer.

ABSTRACT

PURPOSE OF REVIEW Prostate cancer is the most frequently diagnosed non-cutaneous malignancy of men in the USA; notably, the incidence is higher among men of African, followed by European and Asian ancestry. Germline mutations and, in particular, mutations in DNA damage repair genes (DDRGs) have been implicated in the pathogenesis of prostate cancer. This review intends to discuss the implication of ancestry on prostate cancer, specifically in regard to lack of diversity in genomic and genetic databases and the ability of providers to properly counsel patients on the significance of cancer genetic results. RECENT FINDINGS: Ancestral differences in prostate cancer-associated DDRG germline mutations are increasingly recognized. Guidelines for treatment by the National Comprehensive Cancer Network® (NCCN®) support germline testing in certain patients, and a myriad of genetic testing panels for DDRG mutations are now available in clinical practice. However, the consensus among providers on what genes and mutations to include in the genetic tests has evolved from experience from men of European ancestry (EA). Gaps in ancestry-informed clinical practice exist in genetic risk assessment, implementation of screening, counseling, guiding recommendations, treatment, and clinical trial enrollment. The lack of diversity in tumor genomic and genetic databases may hinder ancestry-specific disease-predisposing alterations from being discovered and targeted in prostate cancer and, therefore, impede the ability of providers to accurately counsel patients on the significance of cancer genetic test results.