AbstractBackgroundGenetic testing for pancreatic ductal adenocarcinoma (PDAC) patients is in constant development. However, the status of homologous recombination repair (HRR) genes in unselected Chinese PDAC has not been fully explored. This study aims to characterize the profile of germline mutations in HRR genes in Chinese PDAC patients.MethodsA cohort of 256 PDAC patients were enrolled at Zhongshan Hospital Fudan University between 2019 and 2021. Germline DNA was analyzed by next‐generation sequencing using a multigene panel of the 21 HRR genes.ResultsThe germline pathogenic (P)/likely pathogenic (LP) variant rates were 7.0% (18/256) in unselected patients with pancreatic cancer. Among them, 1.6% (4/256) were identified as harboringBRCA2variants, and 5.5% (14/256) patients carried non‐BRCA variants. Variants were detected in eight non‐BRCA genes, includingATM(4, 1.6%),PALB2(4, 1.6%),ATR(1, 0.4%),BRIP1(1, 0.4%),CHEK2(1, 0.4%),MRE11(1, 0.4%),PTEN(1, 0.4%), andSTK11(1, 0.4%).ATM,BRCA2, andPALB2were the most prevalent variant genes. If onlyBRCA1/2was tested, 5.5% of P/LP variants would have been lost. Further, we found that the landscape of P/LP HRR variants in various population cohorts was quite different. However, no significant difference was found in clinical characteristics between germline HRR P/LP carriers and non‐carriers. In our study, one case carrying a germlinePALB2variant showed a long‐time response to platinum‐based chemotherapy and PARP inhibitor.ConclusionThis study comprehensively depicts the prevalence and characteristics of germline HRR mutations in unselected Chinese PDAC patients. Our findings show the clinical utility of a multigene panel may increase the detection of P/LP HRR carriers.