Proton Pump Inhibitors Use and the Risk of Pancreatic Cancer: Evidence from Eleven Epidemiological Studies, Comprising 1.5 Million Individuals

SIMPLE SUMMARY: Proton pump inhibitors are commonly prescribed medications for gastrointestinal disorders, which bring gastric acid down to normal levels. However, the effects of PPI on pancreatic risk remain unclear. Therefore, we conducted a systematic review and meta-analysis to investigate the association between PPI use and pancreatic cancer. The overall combined estimate suggested that PPI therapy was significantly associated with an increased risk of pancreatic cancer (RR(adj.) 1.63, 95%CI: 1.19–2.22, p = 0.002). However, this effect might be biased due to users’ definitions, exposure periods, and other confounding factors. Large epidemiological studies with controlled bias are therefore warranted to confirm or refute the association found in this study. Considering the possible carcinogenic effect of PPI, physicians should be vigilant when prescribing high-dose or long-term PPI. ABSTRACT: Previous epidemiological studies have shown that proton pump inhibitor (PPI) may modify the risk of pancreatic cancer. We conducted an updated systematic review and meta-analysis of observational studies assessing the effect of PPI on pancreatic cancer. PubMed, Embase, Scopus, and Web of Science were searched for studies published between 1 January 2000, and 1 May 2022. We only included studies that assessed exposure to PPI, reported pancreatic cancer outcomes, and provided effect sizes (hazard ratio or odds ratio) with 95% confidence intervals (CIs). We calculated an adjusted pooled risk ratio (RR) with 95%CIs using the random-effects model. Eleven studies (eight case–control and three cohorts) that reported 51,629 cases of pancreatic cancer were included. PPI was significantly associated with a 63% increased risk of pancreatic cancer (RR(adj.) 1.63, 95%CI: 1.19–2.22, p = 0.002). Subgroup analysis showed that the pooled RR for rabeprazole and lansoprazole was 4.08 (95%CI: 0.61–26.92) and 2.25 (95%CI: 0.83–6.07), respectively. Moreover, the risk of pancreatic cancer was established for both the Asian (RR(adj.) 1.37, 95%CI: 0.98–1.81) and Western populations (RR(adj).2.76, 95%CI: 0.79–9.56). The findings of this updated meta-analysis demonstrate that the use of PPI was associated with an increased risk of pancreatic cancer. Future studies are needed to improve the quality of evidence through better verification of PPI status (e.g., patient selection, duration, and dosages), adjusting for possible confounders, and ensuring long-term follow-up.