Liver and Bile
Gastroenterology. 2023;165(1):218–27.e8
Gallstones, cholecystectomy, and kidney cancer: Observational and Mendelian randomization results based on large cohorts
Background and aims: Gallstones (cholelithiasis) constitute a major health burden with high costs related to surgical removal of the gallbladder (cholecystectomy), generally indicated for symptomatic gallstones. The association between gallstones and cholecystectomy and kidney cancer is controversial. The authors comprehensively investigated this association, considering age at cholecystectomy and time from cholecystectomy to kidney cancer diagnosis, and assessed the causal effect of gallstones on kidney cancer risk by Mendelian randomization.
Methods: They compared the risk of kidney cancer in cholecystectomized and non-cholecystectomized patients (16.6 million in total) from the Swedish nationwide cancer, census, patient, and death registries using hazard ratios (HRs). For 2-sample and multivariable Mendelian randomization, summary statistics based on 408,567 UK Biobank participants were used.
Results: During a median follow-up of 13 years, 2627 of 627,870 cholecystectomized Swedish patients developed kidney cancer (HR = 1.17; 95% confidence interval [CI]: 1.12–1.22). Kidney cancer risk was particularly increased in the first 6 months after cholecystectomy (HR = 3.79; 95% CI: 3.18–4.52) and in patients cholecystectomized before the age of 40 years (HR = 1.55; 95% CI: 1.39–1.72). Mendelian randomization results based on 18,417 patients with gallstones and 1788 patients with kidney cancer from the United Kingdom revealed a causal effect of gallstones on kidney cancer risk (9.6% risk increase per doubling in gallstone prevalence; 95% CI: 1.2–18.8%).
Conclusions: Both observational and causal Mendelian randomization estimates based on large prospective cohorts support an increased risk of kidney cancer in patients with gallstones. The findings provide solid evidence for the compelling need to diagnostically rule out kidney cancer before and during gallbladder removal, to prioritize kidney cancer screening in patients undergoing cholecystectomy in their 30s, and to investigate the underlying mechanisms linking gallstones and kidney cancer in future studies.