Abstract
Background
Previous observational studies have identified abnormalities in lipid metabolism among lung cancer patients, but the causal relationship between lipidomes and lung cancer risk remains unclear. Herein, we investigate the causal effect of lipidomes on the incidence of lung cancer and its subtypes through two-sample Mendelian randomization (MR) analysis.
Methods
A genome-wide association study of 179 lipid metabolites was used as the exposure, while lung cancer and its subtypes were the outcomes. All the datasets were obtained from an open database. The inverse variance weighted method was used as the primary analysis, and MR-Egger regression, the weighted median method, and the weighted mode method were employed to test the robustness of the results. MR-Egger intercept and Cochran's Q statistical analysis were used to assess potential pleiotropy and heterogeneity. Leave-one-out sensitivity analysis was also used to test the stability of the findings.
Results
Forty-two significant lipids were identified as causative exposures for lung cancer. Seventeen lipids affected lung cancer risk in smokers, while only four affected non-smokers. There were two overlapping lipids among the three pathological types of lung cancer. Phosphatidylcholine (O-16:1_18:0) had protective effects on small cell lung cancer (odds ratio (OR) = 0.828, P = 0.038) and lung squamous cell carcinoma (LUSC) (OR = 0.859, P = 0.005). Phosphatidylethanolamine (18:0_18:2) also exhibited protective effects on lung adenocarcinoma (OR = 0.943, P = 0.038) and LUSC (OR = 0.912, P = 0.003). Our results were robust even without a single SNP due to a "leave-one-out" analysis. The MR Egger intercept test indicated that genetic pleiotropy had no effect on the results. No heterogeneity was detected by Cochran's Q test.
Conclusion
This study unveiled the causal effect of specific lipid species on lung cancer and its subtypes. Smoking patients are more susceptible to abnormal lipid metabolism and are at a higher risk of developing lung cancer. Different lipid species are closely associated with various pathological types of lung cancer. Our study suggests that lipids may be utilized in the early screening, prevention, and treatment of lung cancer.