Does the Use of Proton Pump Inhibitors Increase the Risk of Pancreatic Cancer? A Systematic Review and Meta-Analysis of Epidemiologic Studies

Abstract

Background: One of the most frequently used medications for treating gastrointestinal disorders is proton pump inhibitor (PPI), which reportedly has potential adverse effects. Although the relationship between the use of PPIs and the risk of pancreatic cancer has been extensively investigated, the results remain inconsistent. Hence, this meta-analysis aimed to evaluate such relationship. Methods: We searched for literature and subsequently included 10 studies (seven case–control and three cohort studies; 948,782 individuals). The pooled odds ratio (OR) and 95% confidence intervals (CI) for pancreatic cancer were estimated using a random-effects model. We also conducted sensitivity analysis and subgroup analysis. Results: The pooled OR of the meta-analysis was 1.698 (95% CI: 1.200–2.402, p = 0.003), with a substantial heterogeneity (I2 = 98.75%, p < 0.001). Even when studies were excluded one by one, the pooled OR remained statistically significant. According to the stratified subgroup analyses, PPI use, and pancreatic cancer incidence were positively associated, regardless of the study design, quality of study, country, and PPI type. Conclusion: PPI use may be associated with the increased risk of pancreatic cancer. Hence, caution is needed when using PPIs among patients with a high risk of pancreatic cancer.

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

“…Previous meta-analyses of observational studies on PPI uses and the risk of pancreatic cancer reported that there was a positive link between them [ 31 , 32 , 33 ], which is consistent with our findings. Laoveeravat et al [ 32 ] included seven studies with a total of 546,199 participants.…”

Association of proton‐pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta‐analyses of cohort studies and randomised controlled trials

“…In total, we identified 6241 articles, scrutinised 375 full‐text articles, and included 132 eligible articles (3.52%) for preliminary data extraction ( Figure S1). After the selection criteria for the overlapping meta‐analyses were applied, 61 articles were ultimately selected for evidence synthesis 6–8,31–88 . Agreement between reviewers for eligibility of articles was excellent (κ statistic = 0.8).…”

Metagenomic Identification of Microbial Signatures Predicting Pancreatic Cancer From a Multinational Study

“…However, we identified some overlaps between PDAC-and PPI-associated species, resulting in a somewhat high false positive rate for PPI users (w20%). Given epidemiological evidence of positive associations of PPI use and the risk of PDAC, 54 the overlap of the microbial signatures (eg, increase in Streptococcus spp and Veillonella spp) implies that the gut microbiome altered by PPIs is responsible for the development or progression of PDAC.…”