Abstract
The rising incidence of early-onset pancreatic and biliary tract cancers (PBTCs) challenges conventional assumptions that these malignancies primarily affect older populations. Although early-onset PBTCs have a similarly poor prognosis to later-onset cases, emerging evidence suggests that unique or mixed genetic, environmental, and lifestyle factors contribute to their distinct etiologies. This review synthesizes current data on the epidemiology, risk factors, and molecular features of early-onset (in individuals <50 years of age) pancreatic ductal adenocarcinoma and biliary tract cancers. Recent studies indicate a significant increase in early-onset PBTC incidence, with variations by sex, geographic region, and genetic predisposition. Hereditary factors, including BRCA1/2, CDKN2A, and mismatch repair gene mutations, contribute to familial clustering, while other nonhereditary risk factors such as obesity, smoking, pancreatitis, and diabetes seem to disproportionately impact younger patients. Additionally, environmental exposures, including air pollution, pesticides, and endocrine-disrupting chemicals, are suggested to contribute to carcinogenesis, while changes in microbiota may cause inflammation, immune modulation, and treatment resistance. As the burden of early-onset PBTCs grows, refining screening strategies and integrating microbiome-based risk assessment into biobanking strategies will be critical. Future research should focus on age-stratified genetic risk profiling, microbiota-driven interventions, and personalized therapeutic approaches to improve early detection and patient outcomes.