Obesity and Risk of High-Grade Dysplasia and Gallbladder Cancer Among Women with Gallstones in the Chile Biliary Longitudinal Study
10 affiliations
- 1Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- 2Escuela de Salud Pública, Pontificia Universidad Católica de Chile, Santiago 8330077, Chile
- 3Center for Cancer Prevention and Control (CECAN), Santiago 8331150, Chile
- 4Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
- 5Hospital Dr. Hernán Henríquez Aravena, Temuco 4781151, Chile
- 6Facultad de Medicina, Universidad de La Frontera, Temuco 4781218, Chile
- 7Facultad de Medicina, Universidad Católica del Maule, Talca 3480112, Chile
- 8Independent Researcher, Willis, VA 24380, USA
- 9Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8330077, Chile
- 10Instituto de Salud Pública, Santiago 7780050, Chile
Abstract
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.
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BibTeX
@article{cook2026obesity,
title = {{Obesity and Risk of High-Grade Dysplasia and Gallbladder Cancer Among Women with Gallstones in the Chile Biliary Longitudinal Study}},
author = {Paz Cook and Ruth M. Pfeiffer and Jennifer S. Smith and Juan Carlos Araya and Noldy Mardones and Laura Huidobro and Hector Losada and Allan Hildesheim and Juan Carlos Roa and Claudia Marco and Ian Reyes and Matias Pozo and Catterina Ferreccio and Jill Koshiol and the Chile BiLS Study Group},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203356},
url = {https://www.mdpi.com/2072-6694/18/20/3356},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Obesity and Risk of High-Grade Dysplasia and Gallbladder Cancer Among Women with Gallstones in the Chile Biliary Longitudinal Study
AU - Paz Cook
AU - Ruth M. Pfeiffer
AU - Jennifer S. Smith
AU - Juan Carlos Araya
AU - Noldy Mardones
AU - Laura Huidobro
AU - Hector Losada
AU - Allan Hildesheim
AU - Juan Carlos Roa
AU - Claudia Marco
AU - Ian Reyes
AU - Matias Pozo
AU - Catterina Ferreccio
AU - Jill Koshiol
AU - the Chile BiLS Study Group
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18203356
UR - https://www.mdpi.com/2072-6694/18/20/3356
AB - 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.
SN - 2072-6694
ER -