Increased Risk of Pancreatic Cancer Related to Gallstones and Cholecystectomy: A Systematic Review and Meta-Analysis

To investigate the potential roles of gallstones and cholecystectomy in pancreatic carcinogenesis, we performed the first meta-analysis of all currently published studies by pooling relative risks (RRs) with 95% confidence intervals (95% CIs). Stratified analysis by ethnicity, study design, and common adjusted factors were also conducted. Individuals with a history of gallstones and cholecystectomy were at increased risk of pancreatic cancer (RR, 1.39; 95% CI, 1.28-1.52; P < 0.001). Gallstones and cholecystectomy were also associated with an elevated risk of pancreatic cancer, respectively (for gallstones: RR, 1.70; 95% CI, 1.30-2.21; P < 0.001; for cholecystectomy: RR, 1.31; 95% CI, 1.19-1.43; P < 0.001). The positive association is observed among not only the Asian population but also whites. The pooled findings were further confirmed by sensitivity analysis and stratified analyses in case-control and cohort studies. Stratified analyses by different adjusted factors further showed that the increased risk of pancreatic cancer was independent of confounders including diabetes, obesity, smoking, and follow-up years of postcholecystectomy. A history of gallstones and cholecystectomy is a robust risk factor for pancreatic cancer. Gallstone disease or cholecystectomy alone is also an independent risk factor for pancreatic carcinogenesis.