Rare Germline Pathogenic Variants Identified by Multigene Panel Testing and the Risk of Aggressive Prostate Cancer.

摘要: While gene panel sequencing is becoming widely used for cancer risk prediction, its clinical utility with respect to predicting aggressive prostate (PrCa) limited by our current understanding of the genetic factors associated predisposition this potentially lethal disease phenotype. This study included 837 men diagnosed PrCa and 7261 controls (unaffected who did not meet criteria PrCa). Rare germline pathogenic variants (including likely variants) were identified targeted 26 known or putative genes. We found that 85 (10%) 265 (4%) carried a variant (p < 0.0001). Aggressive odds ratios (ORs) estimated using unconditional logistic regression. Increased (OR (95% confidence interval)) was in BRCA2 (5.8 (2.7-12.4)), BRCA1 (5.5 (1.8-16.6)), ATM (3.8 (1.6-9.1)). Our provides further evidence rare these genes are increased aggressive, clinically relevant subset PrCa. These could be incorporated into prediction models improve their precision identify at highest newly require urgent treatment.