Type 2 diabetes and the risk of gastrointestinal cancers in individuals with metabolic dysfunction associated steatotic liver disease.

493 Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), accompanied by type 2 diabetes mellitus, is linked to an increased risk of liver and cardiovascular complications compared to MASLD without diabetes; however, the association with gastrointestinal cancer risk remains largely understudied. Methods: We conducted a population-based retrospective cohort study using the TriNetX platform, which aggregates de-identified electronic health records from healthcare organizations across the United States. Individuals with MASLD were stratified based on the presence or absence of type 2 diabetes mellitus. The primary outcomes included gastrointestinal cancers and their subtypes, assessed over a 5-year follow-up period using Cox proportional hazards regression models. Results: Among matched MASLD patients, those with T2DM had a higher 5-year incidence of all GI cancers (1.6% vs. 0.8%; HR 1.71, 95% CI: 1.56–1.88). The increased risk was most pronounced for liver cancer (0.6% vs. 0.2%; HR 2.32, 95% CI: 1.94–2.76), pancreatic cancer (0.4% vs. 0.2%; HR 1.86, 95% CI: 1.51–2.28), and intrahepatic bile duct cancer (0.1% vs. 0.0%; HR 1.92, 95% CI: 1.31–2.80). No statistically significant differences were observed for other GI cancer subtypes. Conclusions: T2DM was independently associated with a significantly increased risk of several GI cancers among MASLD patients, especially liver, pancreatic, and intrahepatic bile duct cancers. These findings support enhanced cancer surveillance in this high-risk group. 5-year incidence of clinical outcome with type 2 diabetes and without type 2 diabetes in individuals with metabolic dysfunction-associated steatotic liver disease. Outcome MASLD with T2DM Events N (%) MASLD without T2DM Events N (%) Hazard Ratio (95% CI) p-value Gastrointestinal cancer 1,354 (1.6%) 650 (0.8%) 1.71 (1.56−1.88)