S38 Evolving Risk Profiles in Pancreatic Cancer: United States Trends in Mortality Attributable to Smoking and Hyperglycemia (2000 to 2021)

Introduction: Pancreatic cancer remains one of the most lethal gastrointestinal malignancies, with a 5-year survival rate below 10%. As gastroenterologists increasingly participate in the surveillance and risk assessment of patients at elevated risk of pancreatic cancer, particularly through diagnostic procedures and management of comorbid gastrointestinal (GI) conditions, understanding evolving contributors to mortality is essential. This study examines trends in pancreatic cancer mortality attributable to 2 significant risk factors: smoking and high fasting plasma glucose (HFPG) in the United States from 2000 to 2021. Methods: We analyzed age-adjusted pancreatic mortality rates attributable to smoking and high fasting plasma glucose from 2000 to 2021 utilizing the Global Burden of Disease (GBD) database. Temporal trends were evaluated using joinpoint regression to calculate annual percent changes (APC) and average annual percentage changes (AAPC), with statistical significance set at P < 0.05. Results: Pancreatic cancer mortality attributable to smoking showed a modest but statistically significant increase from 2003 to 2016 (APC: 0.45%, P < 0.05), followed by a plateau from 2016 to 2021. In contrast, mortality attributable to HFPG rose sharply between 2000 and 2005 (APC: 3.83%, P < 0.05) and continued to increase through 2021, albeit more gradually (APC: 2.06%, P < 0.05). Over the entire period, the AAPC for HFPG (2.86%, P < 0.05) significantly exceeded that of smoking (0.71%, P < 0.05), indicating a shift in dominant risk factors. Conclusion: Our study highlights the shifting landscape of pancreatic cancer mortality risk factors. While smoking-related deaths have stabilized-likely reflecting effective public health policies-the contribution of hyperglycemia has risen consistently. The sustained rise in mortality linked to hyperglycemia reveals a growing and underrecognized burden. Interestingly, HFPG emerged as a dominant contributor with a consistently higher AAPC across the study period. This trend emphasizes the urgent need to integrate metabolic health strategies into GI cancer prevention frameworks. Gastroenterologists are uniquely positioned to integrate metabolic and lifestyle counseling in the care of patients at risk for GI malignancies.