Gallstones, cholecystectomy and kidney cancer: observational and Mendelian randomisation results based on large cohorts.

Kharazmi, Elham; Scherer, Dominique; Boekstegers, Felix; Liang, Qunfeng; Sundquist, Kristina; Sundquist, Jan; Fallah, Mahdi; Bermejo, Justo Lorenzo (2023). Gallstones, cholecystectomy and kidney cancer: observational and Mendelian randomisation results based on large cohorts. Gastroenterology, 165(1), 218-227 e8. Elsevier 10.1053/j.gastro.2023.03.227

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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, cholecystectomy and kidney cancer is controversial. We comprehensively investigated this association, considering age at cholecystectomy and time from cholecystectomy to kidney cancer diagnosis, and assessing the causal effect of gallstones on kidney cancer risk by Mendelian randomisation (MR).

METHODS

We compared the risk of kidney cancer in cholecystectomised and non-cholecystectomised individuals (16.6 million in total) from the Swedish nationwide cancer, census, patient and death registries using hazard ratios (HRs). For two-sample and multivariable MR, we used summary statistics based on 408,567 UK Biobank participants.

RESULTS

During a median follow-up of 13 years, 2,627 of 627,870 cholecystectomised Swedish patients developed kidney cancer (HR=1.17, 95% 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 cholecystectomised before age 40 (HR=1.55, 95% CI 1.39-1.72). MR results based on 18.417 gallstone and 1,788 kidney cancer patients from the UK 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 MR estimates based on large prospective cohorts support an increased risk of kidney cancer in gallstone patients. Our findings provide solid evidence for the compelling need to diagnostically rule out kidney cancer before and during gallbladder removal, to prioritise kidney cancer screening in patients undergoing cholecystectomy in their 30s, and to investigate the underlying mechanisms linking gallstones and kidney cancer in future studies.

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