同源重组基因与胃癌
, Homologous-Recombination Genes, and Gastric Cancer.
机构信息
From the Laboratories for Genotyping Development (Y.U., M.E., Y.I., T.A., N.H., S.T., K. Suzuki, Y. Momozawa), Statistical and Translational Genetics (C.T.), and Cancer Genomics (H.N.), RIKEN Center for Integrative Medical Sciences, Yokohama, the Divisions of Cancer Information and Control (Y.U., Y.T., Y.N.K., H.I.) and Cancer Epidemiology and Prevention (Y. Kasugai, I.O., K. Matsuo), Department of Preventive Medicine, Aichi Cancer Center, the Divisions of Cancer Epidemiology (Y. Kasugai, K. Matsuo) and Descriptive Cancer Epidemiology (H.I.), Nagoya University Graduate School of Medicine, Aichi Cancer Center Research Institute (I.I.), and the Department of Endoscopy (T.T., M.T.), Aichi Cancer Center Hospital (Y.N.), Nagoya, the Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Medical School, Okayama (Y.U.), the Laboratory of Microbial Carcinogenesis, Institute of Microbial Chemistry, Microbial Chemistry Research Foundation (M. Hatakeyama), the Department of Genetic Medicine and Services, National Cancer Center Hospital (M. Hirata, K. Sugano, T.Y.), the Division of Molecular Pathology, Department of Cancer Biology, Institute of Medical Science (M. Hirata, Y. Murakami), and the Laboratories of Complex Trait Genomics (Y. Kamatani) and Clinical Genome Sequencing (K. Matsuda), Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, and the Department of Genetic Medicine, Kyoundo Hospital, Sasaki Foundation (K. Sugano), Tokyo, and the Research Center of Infection-Associated Cancer, Institute for Genetic Medicine, Hokkaido University, Sapporo (M. Hatakeyama) - all in Japan; and the Population Health Program, QIMR (Queensland Institute of Medical Research) Berghofer Medical Research Institute, Brisbane, Australia (A.B.S.).
出版信息
N Engl J Med. 2023 Mar 30;388(13):1181-1190. doi: 10.1056/NEJMoa2211807.
BACKGROUND
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 infection, on the risk of gastric cancer has not been widely evaluated.
METHODS
We 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 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).
RESULTS
Germline pathogenic variants in nine genes (, , , , , , , , and ) were associated with the risk of gastric cancer. We found an interaction between 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 infection and a pathogenic variant had a higher cumulative risk of gastric cancer than noncarriers infected with (45.5% [95% CI, 20.7 to 62.6] vs. 14.4% [95% CI, 12.2 to 16.6]).
CONCLUSIONS
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.).
背景
感染是胃癌的一个已知危险因素。然而，尚未广泛评估癌症易感基因中的种系致病性变异及其与感染相结合对胃癌风险的影响。
方法
我们评估了 27 个癌症易感基因中的种系致病性变异与来自日本生物银行的 10426 例胃癌患者和 38153 例对照的胃癌风险之间的关联。我们还评估了致病性变异和感染状态对胃癌风险的联合影响，并计算了来自爱知县癌症中心医院基于人群的流行病学研究计划（HERPACC）的 1433 例胃癌患者和 5997 例对照的累积风险。
结果
九个基因（、、、、、、、和）中的种系致病性变异与胃癌风险相关。我们发现，HERPACC 样本中，感染与同源重组基因中的致病性变异之间存在交互作用，与胃癌风险相关（交互作用引起的相对超额风险，16.01；95%置信区间[CI]，2.22 至 29.81；P=0.02）。在 85 岁时，感染且携带致病性变异的个体比未携带 感染的个体具有更高的胃癌累积风险（45.5%[95%CI，20.7 至 62.6]比 14.4%[95%CI，12.2 至 16.6]）。
结论
感染改变了与同源重组基因中的种系致病性变异相关的胃癌风险。（由日本医疗研究与发展机构和其他机构资助）。
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