Proton pump inhibitors and histamine-2 receptor antagonists on the risk of pancreatic cancer: a systematic review and meta-analysis

Background: Proton pump inhibitors (PPI) and histamine-2 receptor antagonists (H2RA) have been widely used for multiple purposes. Recent studies have suggested an association between these medications and the risk of pancreatic cancer. However, the results have been inconclusive. Aim: We, therefore, conducted a study to assess the risk of developing pancreatic cancer in patients who used PPI and H2RA. Design: A systematic review and meta-analysis. Methods: A literature search was performed using MEDLINE and EMBASE databases from inception through February 2019. Studies that reported risk ratio comparing the risk of pancreatic cancer in patients who received PPI or H2RA versus those who did not receive treatments were included. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effect generic inverse variance method. Sensitivity analysis, excluding one study at a time, was performed. Results: After screening abstracts from the searching methods, seven studies (six case-control studies and one cohort study) were included in the analysis with total 546 199 participants. Compared to patients who did not take medications, the pooled RR of developing pancreatic cancer in patients receiving PPI and H2RA were 1.73 (95% CI: 1.16-2.57) and 1.26 (95% CI: 1.02-1.57), respectively. However, the sensitivity analysis of PPI changed the pooled RR to 1.87 (95% CI: 1.00-3.51) after a study was dropped out. Likewise, H2RA sensitivity analysis also resulted in non-significant pooled RR. Conclusions: This meta-analysis did not find the strong evidence for the associations between the use of PPI and H2RA and pancreatic cancer.