Abstract
BACKGROUND: Gastroesophageal reflux disease (GERD) is increasingly recognized for its associations with extragastric diseases, yet its potential role in pancreatic cancer (PC) etiology remains underexplored. This study investigates the genetic causal relationship between GERD and PC using Mendelian randomization (MR), a method designed to reduce confounding factors. METHODS: A two-sample MR analysis was conducted using genome-wide association studies (GWAS) data. The inverse variance weighted (IVW) method was applied, with additional sensitivity analyses performed to evaluate pleiotropy and heterogeneity. RESULTS: The IVW analysis demonstrated a significant genetic association between the genetic signature predisposing to GERD and an increased risk of PC (OR: 1.36, 95% CI: 1.04-1.80, P = 0.03). There was no evidence of pleiotropy (P = 0.71) or heterogeneity (P = 0.94). CONCLUSIONS: Our study provides robust genetic evidence supporting that the genetic predisposition to GERD is associated with an increased risk of PC. These findings emphasize the necessity of integrating GERD into PC risk assessments and encourage further research to elucidate the underlying biological mechanisms. This insight holds potential to inform strategies for early detection, prevention, and personalized management of PC in GERD patients.