Association between Gallstones or Cholecystectomy and Upper Gastrointestinal Cancers: 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 September 2024 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 τ 2 statistics. Results This meta-analysis included 15 studies. There was no association between gallstones [RR (95%CI) = 1.05 (0.97-1.14)] or cholecystectomy [RR (95% CI) = 0.99 (0.87-1.13)] and oesophageal cancer; however, both were positively associated with gastric cancer [RR (95% CI) = 1.25 (1.08-1.44); 1.10 (1.05-1.16), 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, cholecystectomy was specifically associated with non-cardia gastric cancer. Endoscopic screening for gastric cancer may be considered among individuals with gallstones or cholecystectomy history. PROSPERO registration: CRD42024563020