Abstract
BACKGROUND: A Two-sample Mendelian randomization (MR) Analysis was used to assess the causal relationship between non-small cell lung cancer (NSCLC) and sepsis. METHOD: Single nucleotide polymorphisms (SNPs) closely associated with NSCLC were utilized as instrumental variables (IVs) in this study. The Inverse Variance Weighted (IVW) method was used as the primary method for MR analysis, supplemented by the Weighted median, Weighted model, and MR-Egger regression method. Sensitivity analysis was conducted to improve result robustness, and data from various sources were validated and integrated. Bonferroni tests were applied to adjust for multiple comparisons. RESULTS: After Bonferroni tests correcting the combined results, MR analysis revealed a significant association between genetically predicted NSCLC and an increased susceptibility to sepsis (odds ratios [OR]: 1.140, 95% confidence interval [CI]: 1.085-1.199, P = 2.61 × 10(- 7)). The combined results demonstrated that NSCLC is associated with a heightened risk of sepsis in patients under 75 years of age (OR: 1.085, 95%CI: 1.037-1.353, P = 3.84 × 10(- 4)). Furthermore, lung adenocarcinoma (LUAD) was found to be potentially associated with an increased susceptibility to sepsis (OR: 1.040, 95% CI: 1.009-1.073, P = 1.16 × 10(- 2)). These results withstood multiple sensitivity analyses, demonstrating their robustness. CONCLUSION: This study confirms that NSCLC can significantly increase susceptibility to sepsis at the genetic level, providing valuable insights for the early identification of individuals at risk for sepsis.