Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer
Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer
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DOI：
10.1056/nejmoa2211807
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发表时间：
2023-03-30
影响因子：
158.5
通讯作者：
Momozawa, Yukihide
中科院分区：
文献类型：
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作者：
Usui, Yoshiaki;Taniyama, Yukari;Momozawa, Yukihide
基因-环境相互作用与胃癌风险已知幽门螺杆菌感染可增加胃癌风险。在这项研究中，携带某些遗传变异并感染H。背景幽门螺杆菌感染是胃癌的一个众所周知的危险因素。然而，生殖系致病性变异在癌症易感基因中的作用及其与H。幽门螺杆菌感染对胃癌的危险性尚未得到广泛评估。我们评估了27个癌症易感基因的生殖系致病性变异与胃癌风险之间的关联，样本来自日本生物银行的10，426名胃癌患者和38，153名对照。我们还评估了致病性变异体和H. pylori感染状态对胃癌风险的影响，并计算了来自爱知癌症中心医院流行病学研究计划（HERPACC）的1433例胃癌患者和5997例对照的累积风险。结果APC、ATM、BRCA 1、BRCA 2、CDH 1、MLH 1、MSH 2、MSH 6和PALB 2等9个基因的生殖系致病性变异与胃癌的发生有关。我们发现H.幽门螺杆菌感染和同源重组基因中的致病性变异与HERPACC样本中胃癌风险相关（由于相互作用导致的相对超额风险，16.01; 95%置信区间[CI]，2.22 - 29.81; P=0.02）。在85岁时，H. pylori感染和致病性变异体的胃癌累积风险高于感染H.幽门螺杆菌（45.5% [95% CI，20.7至62.6] vs. 14.4% [95% CI，12.2至16.6]）。结论H.幽门螺杆菌感染改变了与同源重组基因中生殖系致病变异相关的胃癌风险。（由日本医学研究开发机构和其他机构资助。
Gene-Environment Interactions and the Risk of Gastric CancerInfection with Helicobacter pylori is known to confer a risk of gastric cancer. In this study, persons who carried certain genetic variants and were infected with H. pylori had an excess risk of gastric cancer.BackgroundHelicobacter pylori infection is a well-known risk factor for gastric cancer. However, the contribution of germline pathogenic variants in cancer-predisposing genes and their effect, when combined with H. pylori infection, on the risk of gastric cancer has not been widely evaluated. MethodsWe evaluated the association between germline pathogenic variants in 27 cancer-predisposing genes and the risk of gastric cancer in a sample of 10,426 patients with gastric cancer and 38,153 controls from BioBank Japan. We also assessed the combined effect of pathogenic variants and H. pylori infection status on the risk of gastric cancer and calculated the cumulative risk in 1433 patients with gastric cancer and 5997 controls from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC). ResultsGermline pathogenic variants in nine genes (APC, ATM, BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, and PALB2) were associated with the risk of gastric cancer. We found an interaction between H. pylori infection and pathogenic variants in homologous-recombination genes with respect to the risk of gastric cancer in the sample from HERPACC (relative excess risk due to the interaction, 16.01; 95% confidence interval [CI], 2.22 to 29.81; P=0.02). At 85 years of age, persons with H. pylori infection and a pathogenic variant had a higher cumulative risk of gastric cancer than noncarriers infected with H. pylori (45.5% [95% CI, 20.7 to 62.6] vs. 14.4% [95% CI, 12.2 to 16.6]). ConclusionsH. pylori infection modified the risk of gastric cancer associated with germline pathogenic variants in homologous-recombination genes. (Funded by the Japan Agency for Medical Research and Development and others.)