Zhou Jiejun, Zhang Youqian, Yang Tian, Zhang Kun, Li Anqi, Li Meng, Peng Xiaojing, Chen Mingwei
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Health Science Center, Yangtze University, Jingzhou, Hubei, China.
Front Genet. 2024 Jun 28;15:1381303. doi: 10.3389/fgene.2024.1381303. eCollection 2024.
Former research has emphasized a correlation between lung cancer (LC) and sepsis, but the causative link remains unclear.
This study used univariate Mendelian Randomization (MR) to explore the causal relationship between LC, its subtypes, and sepsis. Linkage Disequilibrium Score (LDSC) regression was used to calculate genetic correlations. Multivariate MR was applied to investigate the role of seven confounding factors. The primary method utilized was inverse-variance-weighted (IVW), supplemented by sensitivity analyses to assess directionality, heterogeneity, and result robustness.
LDSC analysis revealed a significant genetic correlation between LC and sepsis (genetic correlation = 0.325, = 0.014). Following false discovery rate (FDR) correction, strong evidence suggested that genetically predicted LC (OR = 1.172, 95% CI 1.083-1.269, = 8.29 × 10, = 2.49 × 10), squamous cell lung carcinoma (OR = 1.098, 95% CI 1.021-1.181, = 0.012, = 0.012), and lung adenocarcinoma (OR = 1.098, 95% CI 1.024-1.178, = 0.009, = 0.012) are linked to an increased incidence of sepsis. Suggestive evidence was also found for small cell lung carcinoma (Wald ratio: OR = 1.156, 95% CI 1.047-1.277, = 0.004) in relation to sepsis. The multivariate MR suggested that the partial impact of all LC subtypes on sepsis might be mediated through body mass index. Reverse analysis did not find a causal relationship ( > 0.05 and > 0.05).
The study suggests a causative link between LC and increased sepsis risk, underscoring the need for integrated sepsis management in LC patients.
既往研究强调了肺癌（LC）与脓毒症之间的相关性，但因果关系仍不明确。
本研究采用单变量孟德尔随机化（MR）来探讨LC及其亚型与脓毒症之间的因果关系。使用连锁不平衡评分（LDSC）回归来计算遗传相关性。应用多变量MR来研究七个混杂因素的作用。主要使用的方法是逆方差加权（IVW），并辅以敏感性分析来评估方向性、异质性和结果稳健性。
LDSC分析显示LC与脓毒症之间存在显著的遗传相关性（遗传相关性 = 0.325，P = 0.014）。经过错误发现率（FDR）校正后，有力证据表明，遗传预测的LC（比值比[OR] = 1.172，95%置信区间[CI] 1.083 - 1.269，P = 8.29×10⁻⁶，Q = 2.49×10⁻⁴）、肺鳞状细胞癌（OR = 1.098，95% CI 1.021 - 1.181，P = 0.012，Q = 0.012）和肺腺癌（OR = 1.098，95% CI 1.024 - 1.178，P = 0.009，Q = 0.012）与脓毒症发病率增加有关。对于小细胞肺癌与脓毒症的关系也发现了提示性证据（Wald比值：OR = 1.156，95% CI 1.047 - 1.277，P = 0.004）。多变量MR表明，所有LC亚型对脓毒症的部分影响可能通过体重指数介导。反向分析未发现因果关系（P > 0.05且Q > 0.05）。
该研究表明LC与脓毒症风险增加之间存在因果关系，强调了对LC患者进行综合脓毒症管理的必要性。
