Denture use is associated with a higher risk of cholelithiasis: a prospective cohort study

OBJECTIVES: To investigate whether denture use is associated with an increased risk of cholelithiasis and to examine the combined effects of denture use and genetic susceptibility on cholelithiasis risk. METHODS: This prospective cohort study included 446,743 participants free of cholelithiasis at baseline from the UK Biobank. Denture use was assessed via touchscreen questionnaire at baseline. Incident cholelithiasis was identified through hospital records. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Polygenic risk scores (PRS) for cholelithiasis were constructed to assess genetic susceptibility. Mediation analysis was performed to quantify the contributions of metabolic and dietary pathways. Joint analyses with oral symptoms were conducted to disentangle denture use from concurrent oral diseases. Two-sample Mendelian randomization (MR) was used to evaluate potential causality. RESULTS: Over a median follow-up of 13.69 years, 16,715 incident cholelithiasis cases were documented. Denture use was associated with a 29% higher risk of cholelithiasis after full adjustment (HR = 1.29, 95% CI: 1.24-1.34). The risk was highest among denture users with high genetic risk (HR = 1.57, 95% CI: 1.43-1.71). No multiplicative or additive interaction was observed between denture use and genetic risk. In joint analyses, denture use alone was associated with substantially higher risks than oral symptoms alone, with a significant dose-response gradient across ordered categories (P for trend < 0.001). Mediation analysis showed that BMI mediated 12.96% of the total association, while dietary characteristics mediated less than 1%. MR analysis supported a potential causal relationship (IVW OR = 1.97, 95% CI: 1.05-3.70). Results remained robust across multiple sensitivity analyses. CONCLUSIONS: Denture use was independently associated with a higher risk of cholelithiasis, regardless of genetic susceptibility. The association persisted after accounting for oral symptoms. These findings identify denture use as a novel factor that may contribute to cholelithiasis risk and suggest a potential role of oral health surveillance in gallstone prevention.