摘要Objective: To reveal the distribution signature of cancer susceptibility genes in patients with gastric adenocarcinoma,offering a diagnostic and prognostic surrogate for disease risk management and therapeutic decisions.Methods: A total of 282 patients with gastric adenocarcinoma (182 males and 100 females) were enrolled in this study,with peripheral blood genomic DNA extracted.Mutations of 69 canonical cancer susceptibility genes or presumably tumor-related genes were analyzed by targeted capture-based high-throughput sequencing.Candidate mutations were particularly selected for discussion on tumor pathogenesis according to the American College of Medical Generics and Genomics (ACMG) guidelines.Results: In this study,7.1％ (20/282) of patients with gastric adenocarcinoma were found to harbor mutations of canonical or presumable cancer susceptibility genes.The detection rate in male patients (3.8％,7/182) was significantly lower than that in female patients (13％,13/100) (P=0.004).The most recurrent mutations were in AT mutated (ATM) (1.1％,3/282),followed by BRCA1,BRIP1 and RAD51D,all showed a detection rate of 0.7％ (2/282).Mutations in three genes associated with hereditary gastric cancer syndromes were detected,namely,PMS2 and EPCAM associated with Lynch syndrome and CDH1 associated with hereditary diffuse gastric cancer.The detection frequencies were all 0.4％ (1/282).Notwithstanding no significant difference observed,the age of patients with pathogenic mutations or likely pathogenic mutations is slighdy younger than that of non-carriers (median age: 58.5 vs.60.5 years old),while the age of patients with ATM mutations was the youngest overall (median age: 49.3 years old).Conclusions: Our study shed more light on the distribution signature and pathogenesis of mutations in gastric cancer susceptibility genes,and found the detection rate of pathogenic and likely pathogenic mutations in male patients was significantly lower than that in female patients.Some known and unidentified mutations were found in gastric cancer,which allowed us to gain more insight into the hereditary gastric cancer syndromes from the molecular perspective.