Abstract / Summary
Gallbladder cancer (GBC) is an uncommon but highly lethal malignancy, characterized by striking geographic clustering, late diagnosis, and a prevention profile that differs from other gastrointestinal malignancies. This narrative review synthesizes epidemiologic, mechanistic, clinical, and public-health evidence on GBC determinants with a prevention-oriented lens. Rather than merely cataloguing risk factors, we propose a pragmatic framework that combines epidemiologic credibility, population-attributable burden, baseline risk, biologic plausibility, feasibility, and the benefit-risk balance of possible interventions. The strongest opportunities for prevention arise from risk-stratified management of gallbladder disease and congenital biliary abnormalities, reduction of excess and dysfunctional adiposity, promotion of physical activity, control of chronic Salmonella carriage in endemic settings, and mitigation of selected food- and water-borne toxic exposures. Several other determinants, including diet, alcohol consumption, smoking, reproductive factors, and socioeconomic disadvantage, may inform risk stratification or broader cancer-prevention policy, but currently offer less specific actionability. Effective prevention will require matching interventions to context: population-wide metabolic and lifestyle prevention, targeted clinical management of high-risk gallbladder conditions, and endemic-area strategies addressing infection, environmental exposure, and access to surgery. GBC prevention is therefore possible through carefully evaluated risk-adapted strategies.