Association between gallstones or cholecystectomy and upper gastrointestinal cancer risk: a systematic review and meta-analysis

Abstract Background Gallstones and cholecystectomy may be associated with upper gastrointestinal cancer risk but findings from individual studies are inconsistent. We undertook a systematic review and meta-analysis of available evidence. Methods PubMed/MEDLINE and Embase were searched through April 2026 to identify case-control and cohort studies investigating gallstones or cholecystectomy and oesophageal or gastric cancer risk. Random effects models estimated pooled relative risks (RRs) and 95% confidence intervals (CIs) for oesophageal and gastric cancer. Heterogeneity was evaluated using I 2 and $$\:\tau\:$$ 2 statistics. Results This meta-analysis included 17 studies. There was no association between gallstones [RR (95%CI) = 1.05 (0.97–1.14)] or cholecystectomy [RR (95% CI) = 0.98 (0.88–1.11)] and oesophageal cancer; however, both were positively associated with gastric cancer [RR (95% CI) = 1.25 (1.08–1.44); 1.11 (1.06–1.15), respectively]. In subgroup analyses, cholecystectomy was positively associated with non-cardia [RR (95%CI) = 1.17 (1.04–1.33)] but not cardia gastric cancer [RR (95% CI) = 0.89 (0.78–1.02)]; there were no other statistically significant associations by subtype/subsite, however data were limited for some subgroups. Conclusions Gallstones and cholecystectomy were positively associated with gastric cancer and cholecystectomy was specifically associated with non-cardia gastric cancer. Additional large-scale longitudinal studies are needed to clarify associations by cancer subtype and subsite.