Meta-analysis links gallstones and cholecystectomy to gastric cancer

A systematic review and meta-analysis of 17 studies found that gallstones and cholecystectomy were associated with a modestly higher risk of gastric cancer, while neither was statistically associated with oesophageal cancer. The pooled relative risk for gastric cancer was 1.25 (95% confidence interval, 1.08–1.44) for gallstones and 1.11 (1.06–1.15) for cholecystectomy. These estimates describe associations in the included evidence and do not establish that either gallstones or gallbladder removal causes cancer.

Researchers searched PubMed/MEDLINE and Embase through April 2026 to identify case-control and cohort studies investigating gallstones or cholecystectomy in relation to oesophageal and gastric cancer. They used random-effects models to estimate pooled relative risks and 95% confidence intervals. Variation among studies was evaluated with the I² and τ² statistics. The review focused on upper gastrointestinal cancers, reporting separate results for oesophageal cancer, gastric cancer overall and selected gastric cancer subtypes and anatomical subsites.

For oesophageal cancer, the meta-analysis found no statistically significant association with either exposure. The pooled relative risk was 1.05 (95% CI, 0.97–1.14) for gallstones and 0.98 (0.88–1.11) for cholecystectomy. By contrast, both measures were positively associated with gastric cancer. The gallstone estimate corresponded to a 25% higher pooled relative risk, whereas the cholecystectomy estimate corresponded to an 11% higher pooled relative risk. The study reported the numerical results but did not establish a causal relationship between the exposures and the outcomes.

Results for cholecystectomy differed when gastric cancer was divided into cardia and non-cardia groups. Cholecystectomy was positively associated with non-cardia gastric cancer, with a pooled relative risk of 1.17 (95% CI, 1.04–1.33). The estimate for gastric cardia cancer was 0.89 (95% CI, 0.78–1.02), which did not show a statistically significant association. No other associations were statistically significant in subgroup analyses by cancer subtype or subsite, and the authors noted that data were limited for some of these subgroup estimates.

The overall pattern was therefore specific to gastric cancer rather than oesophageal cancer in the evidence reviewed. Gallstones and cholecystectomy each had a statistically significant pooled association with gastric cancer, while cholecystectomy was associated with non-cardia gastric cancer but not gastric cardia cancer. The investigators said that additional large-scale longitudinal studies are needed to clarify the associations by cancer subtype and subsite. Until that evidence develops, the results should be understood as pooled observational associations with uncertainty that is especially notable in some subgroup analyses.

Subject of Research: Associations of gallstones and cholecystectomy with oesophageal and gastric cancer risk

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

Article References: Li, F., Murphy, G. A., Mortell, G., Cross, A. J., & Harewood, R. (2026). Association between gallstones or cholecystectomy and upper gastrointestinal cancer risk: a systematic review and meta-analysis. BMC Cancer. https://doi.org/10.1186/s12885-026-16781-x

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16781-x

Keywords: gallstones, cholecystectomy, gastric cancer, oesophageal cancer, non-cardia gastric cancer, systematic review, meta-analysis, cancer risk, relative risk, Association, between, upper