Germline sequencing analysis to inform clinical gene panel testing for aggressive prostate cancer

Germline gene panel testing for prostate cancer (PrCa) is recommended for men with advanced disease to guide treatment and disease management decisions and for unaffected men with a cancer family history to inform screening decisions. Current gene panels are likely to be incomplete and missing genes that influence PrCa risk and aggressive disease. Pooled analysis of 18 trials with 17,546 men with aggressive and non aggressive PrCa found an association between deleterious variants in known genes BRCA2, ATM, and NBN with aggressive PrCa. Nominal associaton evidence was observed for MSH2, XRCC2, and MRE11A. The authors conclude that the findings of this analysis suggest that DNA repair and cancer susceptibility genes can inform disease management in men with nonaggressive PrCa, as men carrying deleterious variants in these genes are likely to develop advanced disease.