44Association Between Diabetes and Gallbladder Cancer Risk Among Chilean Women with Gallstones: Findings from the Chile Biliary Longitudinal Study
Rime Jebai, Ruth M Pfeiffer, Paz Cook, Allan Hildesheim, Catterina Ferreccio, Juan Carlos Araya, Jill KoshiolAbstract
Background
Gallbladder cancer (GBC) is a highly lethal malignancy with particularly high incidence in Chile, especially among women. While gallstones are known to be a major risk factor, most individuals with gallstones never develop GBC. Diabetes mellitus has emerged as a risk modifying factor among those with gallstones, although it is unclear whether diabetes increases risk of stones or of neoplasia given the presence of stones. This study examined the association between diabetes and GBC risk among Chilean women with gallstones.
Methods
The Chile Biliary Longitudinal Study cohort enrolled 4,711 women aged 50-74 years with ultrasound-detected gallstones from south-central Chile (2016-2019). Diabetes status was self-reported at baseline. Incident gallbladder dysplasia and cancer were identified through pathology reports and death registry linkage. Outcomes were classified as: cholecystectomized GBC (diagnosed at cholecystectomy), clinical GBC (diagnosed during clinic visits), or high-grade dysplasia (HGD; diagnosed at cholecystectomy). Confounders were identified in logistic and Cox proportional hazards regression models. Multivariable-adjusted Cox proportional hazard models estimated hazard ratios (aHRs) and 95% confidence intervals (Cls), overall and stratified by urban/rural residence.
Results
Over a median of 4.8-year follow-up (range=2.0 to 7.7), 120 women (2.5%) were newly diagnosed with GBC. Median age at diagnosis was 59 years; 34% of cases identified as Mapuche (the major ethnic group in the region) and 28% had diabetes. After adjusting for confounders, the overall association with diabetes was aHR=l.2 (95%CI: 0.8-1.9). In stratified models, diabetes was associated with significantly higher GBC/HGD risk among urban women (aHR=2.5; 95%CI:1.4-4.3) but lower risk among rural women (aHR=0.43; 95%CI: 0.19-0.98). For clinical GBC specifically, diabetes was associated with elevated risk overall (aHR=3.4; 95%CI: 1.3-9.0) and among urban women (aHR=8.l; 95%CI: 2.3-28.3). No statistically significant associations were observed for cholecystectomized GBC or HGD either overall or in stratified analyses.
Conclusions
Among Chilean women with gallstones, diabetes was associated with increased GBC risk for those residing in urban settings but lower risk in rural areas. The reasons underlying this urban rural disparity remain unclear and warrant further investigation. Potential explanations may include differences in diabetes management, healthcare access, lifestyle factors, or environmental exposures between urban and rural populations. These preliminary findings suggest that diabetic women with gallstones in urban areas may represent a high-risk population that could benefit from enhanced surveillance, pending confirmation in additional studies.