S185 Predictors of Early-Onset Pancreatic Cancer: A Population-Based Case-Control Study in the United States

Introduction: Early-onset pancreatic cancer (EOPC), defined as pancreatic cancer diagnosed before the age of 50, accounts for 8%-10% of all pancreatic cancer cases and presents unique challenges due to delayed diagnosis and the absence of screening guidelines. Understanding risk factors specific to this population is essential for improving early detection and outcomes. Methods: We conducted a retrospective case-control study using TriNetX, a global database of de-identified electronic health records. Adults aged 18–50 diagnosed with exocrine pancreatic cancer between May 2005 and May 2025 were identified as cases. Individuals without pancreatic cancer served as controls. We excluded all patients with neuroendocrine tumors based on ICD-10 codes. We compared demographic, comorbidities, and genetic mutations between both groups. A P-value < 0.05 was considered statistically significant. Results: A total of 16,375 cases and 4,544,188 controls were analyzed. Caucasians had a higher prevalence of EOPC compared to other racial groups. A history of acute pancreatitis (8.6% vs 0.6%; odds ratio [OR]: 15.13; 95% CI: 14.31–15.99), chronic pancreatitis (7.9% vs 0.2%; OR: 46.72; 95% CI: 43.97–49.64), nicotine dependence (10.5% vs 9.6%; OR: 1.11; 95% CI: 1.05–1.16) and alcohol-related disorders (3.8% vs 2.8%; OR: 1.35; 95% CI: 1.24–1.46) were more prevalent in cases of pancreatic cancer compared to controls. Interestingly, while previous studies reported an association between overweight/obesity and pancreatic cancer, our data showed a decreased prevalence of EOPC these patients (10.6% vs 15.4%; OR: 0.65; 95% CI: 0.62–0.69). KRAS mutations were more frequently reported in cases (0.1% vs 0.0%). Other germline mutations were infrequently tested and not statistically significant in this dataset. Conclusion: Pancreatitis, smoking, alcohol use, racial patterns, and genetic predisposition showed an association with EOPC. This study highlights the need for further research evaluating the specific predictors of EOPC, which could guide targeted screening and prevention strategies.