Circulating levels of interleukins and lung cancer and its subtypes: A Mendelian randomization study

Abstract

Background Interleukins (ILs) are closely linked to the pathogenesis of lung cancer (LC). However, the precise causal relationship between them remains somewhat ambiguous. This study aimed to investigate the potential causal relationships between these ILs and LC based on the two-sample Mendelian randomization (TSMR) research framework. Methods We conducted TSMR analyses using summary dataset from large-scale genome-wide association studies (GWASs). Our primary method is random effects inverse variance weighted (RE-IVW) analysis, which was subsequently adjusted using the Bonferroni correction method. We established that results with p values less than 0.0022 (0.05/23) indicate a significant causal relationship, whereas results with p values between 0.0022 and 0.05 indicate a suggestive causal relationship. Additionally, sensitivity analyses were conducted to verify the robustness of the findings. Results Analysis revealed that IL-18 had a significantly protective effect on LC and shows a suggestive negative correlation with LUAD and LUSC. IL-20 and IL-8 were suggestive positive correlation with both LC and LUAD. Additionally, IL-24 showed had a significantly protective effect on LUSC, while IL-17A and IL-8 were suggestive positive correlation with LUSC. Conclusions and Relevance: Our study support IL-18 had protective effect on LC, and IL-24 showed had protective effect on LUSC, suggesting that these cytokines play a crucial role in disease pathogenesis. This finding underscores the need for further research into these associations to better understand their implications for LC development.