Abstract
OBJECTIVE: The causative relationship between lung cancer subtypes and lipids is yet unknown. This research aims to elucidate the potential causative link connecting lipid levels to lung cancer subtypes, particularly focusing on non-small cell lung cancer (NSCLC), using the Mendelian randomization (MR) method and meta-analysis. METHODS: Summary statistics were obtained from genome-wide association study (GWAS) datasets. A comprehensive MR analysis was performed to explore the causal role of lipids in NSCLC subtypes. To ensure the reliability of the results, an external dataset was used for validation, and a meta-analysis was performed for further synthesis. RESULTS: Two of the 179 lipids examined showed potential causal connection with lung adenocarcinoma (LUAD) and three with lung squamous cell carcinoma (LUSC). Specifically, phosphatidylcholine (PC) (16:0_20:4) and PC (18:0_20:4) might be connected to an elevated risk of LUSC, but PC (18:0_20:2) might be linked to a decreased risk. It was discovered that PC (16:1_20:4) and PC (18:0_20:4) might raise the risk for LUAD. CONCLUSION: Complex lipid metabolic pathways, especially involving PC, are present in NSCLC, and distinct lipid isomers may influence various molecular subtypes in different ways.