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

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.

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.

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.

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.