Arch Public Health. 2026 Jun 6. doi: 10.1186/s13690-026-01977-1. Online ahead of print.
ABSTRACT
BACKGROUND: Gallbladder cancer (GBC) is highly fatal and, unlike most cancers, is more common in women than in men. Most GBC cases have gallstones, but most people with gallstones do not develop GBC. Thus, a critical question is what drives the risk of GBC in the presence of gallstones.
METHODS: We designed a case-control study to complement the Chile Biliary Longitudinal Study (Chile BiLS) cohort, enriching the number of GBC cases and enhancing our ability to evaluate risk factors for GBC. Starting in July 2022, we began to recruit non-cohort prevalent (diagnosed between January 1, 2016, and July 18, 2022) and incident (diagnosed on or after July 19, 2022) GBC cases, as well as patients with high-grade dysplasia (HGD), in a high-risk area of Chile. Individuals with GBC or HGD are considered cases (HGD +). We are matching gallstone cholecystectomy patients to cases at an approximate 1:1 ratio. We also include unmatched controls (adjudicated) who were initially suspected of having cancer but had benign findings on gallbladder pathology. If a case or control is deceased, we conduct proxy interviews to maximize the potential for detailed epidemiological data collection. Through August 31, 2025, we recruited 196 prevalent and 117 incident HGD + cases. Of these cases, 189 (96%) prevalent and 108 (92%) incident cases were diagnosed with GBC. All prevalent and 98.3% of incident cases have matched controls. Participation rates are 70.8% for HGD + cases and 67.8% for matched controls.
DISCUSSION: The Chile BiLS case-control study is conducted in an area with high risk of GBC and a high proportion of people with Mapuche Amerindian ancestry. This study will provide important insights into the factors associated with GBC among people with gallstones. Here, we provide a thorough description of the design of the study, field procedures, and biological resources, as well as research opportunities, which will enable a more complete picture of the etiology of GBC by combining epidemiological, molecular, digital imaging, and clinical data. This study represents a powerful resource for the identification of new targets for cancer prevention and treatment, which are particularly needed in populations at high risk of GBC.
PMID:42251441 | DOI:10.1186/s13690-026-01977-1