Abstract
BACKGROUND: Cholecystectomy is the standard procedure for patients with gallbladder disease, but the causal effect of cholecystectomy on gastrointestinal disease remains unclear.
METHODS: We obtained genome-wide significant levels (p-value < 5 × 10 -8) of genetic variation associated with cholecystectomy as an instrumental variable (IV) and performed Mendelian randomisation (MR) to identify causality on gastrointestinal diseases after cholecystectomy. Dual-sample MR was used to study the causal effect of cholecystectomy on oesophagitis, gastritis, oesophageal cancer, gastric cancer, and colorectal cancer. All data were obtained from public shared databases. The causal effect of cholecystectomy on oesophagitis, gastritis, oesophageal cancer, gastric cancer, pancreatitis, and colorectal cancer was assessed using traditional methods such as simple weighted models, inverse variance weighting, weighted median, and Mendelian randomisation (MR-Egger) regression. We used the multiple residuals and outliers (MR-PRESSO) method and the MR-Egger method to investigate sensitivity. The leave-one-out test was used to determine the effect of outliers. Heterogeneity was calculated by using the Cochran Q statistic and MR-Egger regression in the inverse variance weighting (IVW) method p< 0.05 indicates large heterogeneity.
RESULTS: Based on the IVW results of our MR analysis, we found that cholecystectomy increased the risk of oesophagitis ( odds ratio [OR] =1.06, 95% confidence interval [CI]: 1.01-1.11 P=0.015) the risk of tract cancer ( [OR] =499.06, 95% [CI]: 1.15 -217412.20 P=0.045); risk of gastritis ( [OR] =1.06, 95% [CI]: 1.02-1.11 P=0.003); risk of gastric Helicobacter pylori infection ( [OR] =1.06, 95% [CI]: 1.00 -1.11 P=0.045); and risk of chronic pancreatitis ([OR] =588.92, 95% [CI]: 2.92- 118646.23 P=0.018). In addition, it did not increase the risk of gastric cancer ([OR] =0.6, 95% [CI]: 0.001-49.88 P=0.018), pancreatic cancer ([OR] =0.08, 95% [CI]: 0000.2- 26.53 P=0.40), and colorectal cancer ([OR] =13.70, 95% [CI]: 0.74 -252.22 P=0.08) risk of disease. In addition there was no horizontal pleiotropy or heterogeneity in the exposure and individual outcome analyses.
CONCLUSION: The study suggests that cholecystectomy may increase the risk of oesophagitis, oesophageal cancer, gastritis, and pancreatitis, which should be a clinical concern. In addition, cholecystectomy may not increase the risk of gastric cancer, colorectal cancer, but this conclusion needs further evidence of clinical equivalence.