Early-onset gastrointestinal cancers: comprehensive review and future directions

BACKGROUND: The incidence of early-onset (EO) gastrointestinal (GI) cancers-commonly defined as being diagnosed in patients <50 years of age-is rising at an alarming rate globally. The rising incidence demonstrates a birth cohort effect, implicating environmental factors, such as diet and lifestyle; however, the drivers behind this trend are not yet known. METHODS: A comprehensive narrative review of the literature was conducted, focusing on EO colorectal, oesophagogastric, and pancreatic cancers. Additionally, the literature on less common EO GI cancers, including appendiceal, biliary, and neuroendocrine tumours, was reviewed. Epidemiological trends, risk factors, clinical and molecular characteristics, germline and somatic genetic features, and outcomes across these diseases were examined. RESULTS: EO GI cancers have demonstrated a consistent rise in incidence, which disproportionally affects black, Hispanic, and indigenous populations and women. Though germline pathogenic variants are more common in EO GI cancers compared with average-onset GI cancers, most cases occur sporadically. Modifiable risk factors associated with an increased risk of EO GI cancers include obesity, a Western-pattern diet, non-alcoholic fatty liver disease, smoking, and alcohol use, among others. Across GI cancers, younger patients frequently present with more aggressive disease features and receive more intensive treatment compared with older patients. Survival outcomes are inconsistent across studies. CONCLUSION: EO GI cancers represent clinically distinct disease entities that are associated with unique challenges in screening, management, and survivorship. A better understanding of underlying aetiologies, optimized screening strategies, and improved survivorship support are necessary. Meeting the needs of this growing patient population will require a multidisciplinary, equity-based approach in both clinical care and research.