大约10%的胃癌（GC）与强烈的家族聚集有关，并可归因于基因易感性。同源重组缺陷（HRD）导致基因组不稳定和遗传变异的积累，在癌症的发展和进展中发挥重要作用。我们旨在描绘中国HRD-mut GC患者的生殖突变特征。我们回顾了1135名中国GC患者的基因组测序数据。选择至少在BRCA1、BRCA2、ATM、PALB2、BRIP1、CHEK1、CHEK2、FANCA和FANCL之一发生功能缺失（LoF）生殖突变的患者进行分析。共确定了89名患者存在HRD基因的LoF生殖突变。生殖突变最常见于ATM（30.33%），其次是BRIP1（17.98%），BRCA2（14.61%），BRCA1（12.36%），FANCA（10.11%），PALB2（10.11%），FANCL（6.74%），CHEK1（3.37%）和CHEK2（3.37%）。其中14名HRD-mut患者携带HRD和MMR基因的双重突变，中位年龄为51.5岁。中位年龄的下降要归因于5名HRD+MMR双重突变患者同时携带HRD和MMR基因的突变。HRD+MMR双重突变患者的发病年龄中位数为47岁，显著早于中国GC患者的发病年龄（p = 0.0235）。我们的数据表明，携带HRD和MMR基因的LoF生殖突变可能会导致早发性GC。HRD基因的生殖突变应该引起遗传性GC的研究关注。©作者（或其雇主）2023年。根据CC BY-NC允许再利用。不允许商业重用。由BMJ出版。

Approximately 10% of gastric cancers (GCs) are associated with strong familial clustering and can be attributed to genetic predisposition. Homologous recombination deficiency (HRD) leads to genomic instability and accumulation of genetic variations, playing an important role in the development and progression of cancer. We aimed to delineate the germline mutation characteristics of patients with HRD-mut GC in Chinese.We retrospectively reviewed the genomic sequencing data of 1135 patients with Chinese GC. Patients harbouring at least one loss of function (LoF) germline mutations in BRCA1, BRCA2, ATM, PALB2, BRIP1, CHEK1, CHEK2, FANCA and FANCL were selected for analysis.89 patients were identified with LoF germline mutations of HRD gene. Germline mutations occurred most commonly in ATM (30.33%), followed by BRIP1 (17.98%), BRCA2 (14.61%), BRCA1 (12.36%), FANCA (10.11%), PALB2 (10.11%), FANCL (6.74%), CHEK1 (3.37%) and CHEK2 (3.37%). 14 out of 89 patients with HRD-mut harboured double mutations in HRD and MMR genes, with the median age of 51.5 years. The decreasing median age would be attributed to five patients with HRD+MMR double-muts harbouring mutations in both HRD and MMR genes. The median age of onset of patients with HRD+MMR double-muts is 47, which is significantly earlier than that of Chinese patients with GC (p=0.0235).Our data suggest that carrying both HRD and MMR gene LoF germline mutations may cause early-onset GC. Germline mutations in the HRD gene should be of concern in the study of hereditary GC.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.