Genetics of prostate cancer.

Abstract

Prostate cancer is a highly heritable cancer, with contributions from rare pathogenic variants in prostate cancer predisposition genes (eg, HOXB13, BRCA2) and from common genetic variants throughout the genome. Only HOXB13 has been identified as a prostate cancer risk gene through linkage disequilibrium studies. Cancer predisposition genes in DNA damage repair pathways have been found to contribute to prostate cancer risk-particularly high-risk or metastatic prostate cancers-in family-based, clinic-based, and population-based studies. Polygenic and genomic risk scores based on common genetic variants identified in genome-wide association studies may have greater power to determine cancer risk than scores based on rare pathogenic variants, but the utility of these scores has yet to be rigorously studied prospectively. Individuals with high-risk or metastatic prostate cancers should be offered germline genetic testing to inform familial risk and screening practices, and to identify biomarker-based treatment options such as platinum-based chemotherapy or poly(ADP-ribose) polymerase inhibitors. Much work is needed to increase the use of germline genetic testing in individuals with prostate cancer, to improve equitable access to testing across all ethnic and racial groups, and to study the genomes of non-European ancestral populations in greater numbers to identify additional ancestry-specific risk variants.