Proton Pump Inhibitor Use Increases Pancreatic Cancer Risk: A Systematic Review and Meta-Analysis

Background: several epidemiological studies on whether proton pump inhibitor (PPI) use promotes the occurrence and development of pancreatic cancer have reported conflicting results. Therefore, we aimed to assess the association between PPI use and pancreatic cancer risk by conducting a meta-analysis. Methods: A comprehensive search for relevant studies was conducted until September 10, 2019. Studies that evaluated the association between PPI use and pancreatic cancer risk were included. The odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model. All data analyses were performed using STATA 12.0 software. Results: Eight studies, involving 546,619 participants, were included in the meta-analysis. The pooled OR of pancreatic cancer for PPI use and histamine 2 receptor antagonist (H2AR) use were 1.85 (95% CI: 1.25–2.73) and 1.26 (95% CI: 1.02–1.57), respectively. Obvious heterogeneity could not be clearly explained by the subgroup analysis. We also found that chronic pancreatitis, diabetes, and smoking status were associated with increased risk of pancreatic cancer. Sensitivity analyses confirmed that the results were stable, and Begg’s test indicated that there was no publication bias. Conclusions: There was an 85% increased risk of pancreatic cancer in patients with PPI use. Future large prospective studies are needed to further explore the relationship between PPI use and pancreatic cancer. Funding Statement: This study was supported by National Natural Science Foundation of China (No:81660158); Natural Science Key Project of Jiangxi Province (No: 20161ACB21017); Youth Science Foundation of Jiangxi Province (No: 20151BAB215016, 20161BAB215198) Declaration of Interests: The authors deny any conflict of interest.