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Gallstone disease, ranging from biliary colic to cholecystitis, represents a highly prevalent symptomatic gastrointestinal disorder secondary to gallstone obstruction, affecting up to 25% of adults in Western countries. Having cholestasis secondary to gallstone obstruction or cholecystectomy is associated with increased bile acid secretion in the biliary system, which is thought to induce oxidative damage. The local and systemic inflammation driven by this process may explain the possible association between gallstones and the increased risk of kidney cancer suggested in recent literature.

In this large, prospective population-based study, recently published in , Kharazmi et al. examined the risk of kidney cancer in cholecystectomised and non-cholecystectomised individuals from the Swedish nationwide cancer, census, patient, and death registries during a median follow-up time of 13 years. Among 627,870 cholecystectomised Swedish patients, a total of 2,627 patients developed kidney cancer at an increased 17% relative risk compared to those who did not receive a cholecystectomy (HR 1.17, 95% CI 1.12-1.22).

Patients who received a cholecystectomy before age 40 (HR 1.55, 95% CI 1.29-1.72) and in the first 6 months after cholecystectomy (HR 3.79, 95% CI 3.18-4.52) also had an increased kidney cancer risk. Moreover, a significant causal effect of gallstones on kidney cancer risk was demonstrated when subsequently evaluating data from a large U.K. Biobank cohort using Mendelian randomization analysis, an analytical method to assess the causal effect of an exposure risk on a phenotype outcome using genetic variants as instrumental variables. An increased 9.6% risk of kidney cancer per doubling in gallstone prevalence (95% CI 1.2-18.8) was found in this analysis.

Clinically, this study suggests that there may be an increased risk of kidney cancer among individuals with gallstone disease. The findings on the positive association between genetic susceptibility to gallstones and increased kidney cancer risk increase the value of considering kidney cancer screening in patients undergoing cholecystectomy for their gallstone disease, particularly if they are under the age of 40.

Laura S. Chiu, MD, MPH, is an assistant professor of medicine at Boston University School of Medicine.

You can read an interview with the senior study author here, and the abstract of the study here.