Obesity and Risk of High-Grade Dysplasia and Gallbladder Cancer Among Women with Gallstones in the Chile Biliary Longitudinal Study

Background/Objectives: Gallbladder cancer (GBC) remains a leading cause of cancer death in Chilean women. Gallstones are present in >90% of GBC cases, but few individuals with gallstones develop cancer, suggesting additional factors are needed. Methods: To determine whether obesity increases the risk of progression from gallstones to high-grade dysplasia (HGD) and GBC, we used data from the Chile Biliary Longitudinal Study, 2016–2025, comprising women with ultrasound-detected gallstones in high-incidence regions of Chile.We measured body mass index (BMI) and waist-to-height ratio (WHtR) at baseline and up to two follow-up visits. We used Cox proportional-hazards models with age as the time scale to quantify associations of time-varying BMI and WHtR with HGD/GBC risk. Results: During a median follow-up of 4.8 years, 116 of 4711 women developed HGD/GBC. Time-varying BMI was not significantly associated with HGD/GBC risk (p-overall = 0.11; p-nonlinearity = 0.20). In contrast, time-varying WHtR showed a non-linear association with HGD/GBC (p-overall = 0.02; p-nonlinearity = 0.02). Baseline WHtR and BMI models showed similar patterns of associations. Based on longitudinal WHtR trajectories among cases and lag sensitivity analyses, preclinical disease-related weight loss is unlikely to fully explain the observed associations. Conclusions: In conclusion, central obesity measured by WHtR was non-linearly associated with HGD/GBC risk in this population, suggesting that central adiposity may impact the progression from gallstones to HGD/GBC.