Cholecystitis and cholangiocarcinoma: a two-sample mendelian randomization study

Background In recent years, the incidence of cholangiocarcinoma increases. Epidemiological studies suggest that cholecystitis elevates the risk of hepatobiliary cancer. However, an independent causal relationship remains unrevealed. Observational studies are vulnerable to residual confounders and bias, which compromises causal inference. Our study aimed to evaluate whether cholecystitis is an independent risk factor for cholangiocarcinoma. Methods Instrument variables were identified as independent single nucleotide polymorphisms highly associated with cholecystitis (n = 62). The entire dataset from the Integrative Epidemiology Unit (IEU) public availability genome-wide association studies was utilized to determine outcomes for cholangiocarcinoma (n = 62). In this study, five Mendelian randomization (MR) statistical techniques (Inverse Variance Weighted, MR Egger, Weighted Median, Simple Mode, and Weighted mode) were used. The MR Egger intercept test, leave-one-out analysis, and the funnel plot were all utilized in sensitivity analyses. Results Results of the Inverse Variance Weighted tests genetically predicted that cholecystitis was significantly associated with higher risk of cholangiocarcinoma, with an odds ratio of 1.27 (95% CI: 1.038–1.553; P = 0.02). But the Weighted Median Method, MR Egger Regression, Simple Mode, and Weighted Mode all showed no statistical significance (P > 0.05). Both funnel plots and MR Egger intercepts indicated the absence of any directional pleiotropic effects between cholecystitis and cholangiocarcinoma. Conclusion We found potential evidence of a causal effect between cholecystitis and cholangiocarcinoma, indicating an increased likelihood of cholangiocarcinoma in patients with cholecystitis through mendelian randomization analysis. Our results excepted enhance the management of patients with cholecystitis to decrease the risk of cholangiocarcinoma.