Lung cancer risk in patients with multiple sclerosis: a Mendelian randomization analysis

Background: The relationship of multiple sclerosis (MS) with lung cancer is under debate. Conventional observational studies have reported conflicting findings, but such studies are susceptible to confounding and reverse causation. With a Mendelian Randomization approach, we were able to evaluate the causality between MS and lung cancer. Methods: According to published genome-wide association studies (GWASs), we obtained 35 MS-related single-nucleotide polymorphisms, which were used as instrumental variables in our study. Summary data of individual-level genetic information were obtained from the International Lung Cancer Consortium (ILCCO), with a total of 15,861 controls and 11,348 cases; the latter is composed of patients with lung adenocarcinoma and squamous cell lung cancer. The inverse variance-weighted method was applied to estimate the causation between MS and lung cancer. To further evaluate the pleiotropy, the MR-Egger and Weighted median methods were implemented. Results: The results of MR analysis suggested a causal effect of MS on lung cancer incidence, with evidence of an increased risk for overall lung cancer [odds ratio (OR): 1.0648; 95% confidence interval (CI): 1.0163-1.1156; p = 0.0082]. However, subgroup analyses showed no significant causal relationships between MS and lung adenocarcinoma (OR = 1.0716; 95% CI 0.9840-1.1671, p = 0.1119) and squamous cell lung cancer (OR = 1.0284; 95% CI 0.9575-1.1045, p = 0.4424). In addition, no pleiotropy was found in our study. Conclusion: Our study indicated that MS is a causal risk factor in the development of lung cancer. Further work is needed to elucidate the potential mechanisms.