本研究旨在探讨中国人群DNA双链断裂（DSBs）修复能力、DSBs相关基因的变异与肺癌的发生和预后之间的关系。收集了98名肺癌患者的外周血单核细胞（PBMC）。肺癌患者和 60 名健康人。通过测量依托泊苷治疗后 γ-H2AX 水平的变化来评估个体 DSB 的修复能力。对 PBMC DNA 进行了 45 个 DSB 相关基因的外显子测序。进行逻辑回归分析来检查肺癌风险与 DSB 修复能力以及种系基因变异之间的关系。生存分析采用Cox比例风险回归模型、Kaplan-Meier法和Log-rank检验。DSB修复能力较低预示患肺癌的风险增加（OR=0.94，95%CI=0.917-0.964，P＜0.001） 。在肺癌患者中，较高的 DSB 修复能力与一线治疗期间较短的无进展生存期 (PFS) 相关（HR = 1.80，95% CI = 1.10-3.00，P = 0.031）。携带 BRCA1 突变的患者总生存期 (OS) 较短（HR = 1.92，95% CI = 1.12-3.28，P = 0.018）。 FOXO3 突变患者的 PFS 较短（HR = 4.23，95% CI = 1.44-12.36，P = 0.009）。对接受免疫检查点抑制剂 (ICIs) 治疗的患者的分析表明，LIG4 突变与较短的 PFS 相关（HR = 2.90，95% CI = 1.00-8.10，P = 0.041）。这项研究的结论是，评估 DSB 修复能力有望预测中国人群的肺癌风险和预后。需要对与双链断裂相关的特定基因突变进行进一步的大规模研究和功能验证才能确认。版权所有 © 2024。由 Elsevier B.V. 出版。

This study aims to investigate the association between DNA double-strand breaks (DSBs) repair capacity, variations in DSBs-related genes, and the occurrence and prognosis of lung cancer in the Chinese population.Peripheral blood mononuclear cells (PBMC) were collected from 98 lung cancer patients and 60 healthy individuals. The individual DSBs repair capacity was assessed by measuring changes in γ-H2AX levels after treatment with etoposide. Exonic sequencing of 45 DSBs-related genes was performed on PBMC DNA. Logistic regression analysis was conducted to examine the relationship between lung cancer risk and DSBs repair capacity as well as germlines gene variations. Survival analysis employed the Cox proportional hazards regression model, Kaplan-Meier method, and Log-rank test.Lower DSBs repair capacity predicted an increased risk of developing lung cancer (OR = 0.94, 95 %CI = 0.917-0.964, P＜0.001). Among lung cancer patients, higher DSBs repair capacity was associated with shorter progression-free survival (PFS) during first-line treatment (HR = 1.80, 95 %CI = 1.10-3.00, P = 0.031). Patients with BRCA1 mutations had shorter overall survival (OS) (HR = 1.92, 95 %CI = 1.12-3.28, P = 0.018). Patients with FOXO3 mutations had shorter PFS (HR = 4.23, 95 %CI = 1.44-12.36, P = 0.009). Analysis of patients treated with immune checkpoint inhibitors (ICIs) indicated that LIG4 mutations were associated with shorter PFS (HR = 2.90, 95 %CI = 1.00-8.10, P = 0.041).This study concludes that assessing DSBs repair capacity holds promise for predicting both lung cancer risk and prognosis in the Chinese population. Further large-scale studies and functional validation of specific gene mutations related to double-strand breaks are necessary for confirmation.Copyright © 2024. Published by Elsevier B.V.