A pharmacovigilance study of the association between proton pump inhibitors and tumor adverse events based on the FDA adverse event reporting system database

Background: Proton pump inhibitors (PPIs) are effective treatments for acid-related disorders but may pose tumor risks with long-term use. Current research on PPI-associated tumor adverse events (TAEs) is limited and inconclusive. This study aims to comprehensively analyze the relationship between PPIs and TAEs.

Methods: We analyzed PPI adverse reaction reports from the FDA Adverse Event Reporting System (FAERS) database spanning from 2004 to 2024, focusing on five commonly used PPIs: esomeprazole, pantoprazole, lansoprazole, omeprazole, and rabeprazole. We conducted a disproportionality analysis utilizing the Reporting Odds Ratio (ROR) to identify potential TAEs associated with PPIs. We conducted univariate logistic regression analysis to explore the influencing factors.

Results: A total of 3,133 TAEs were identified, representing 2.36% of all PPI-related adverse events (AEs). The most common TAEs were gastric cancer (19.05%) and malignant neoplasm (7.23%). Disproportionality analysis revealed ten significant TAEs associated with PPIs, including gastric adenocarcinoma and renal cell carcinoma. The median age of those reporting TAEs was 59 (interquartile range [IQR]: 51-70), and 29.70% of them resulted in a fatality. TAEs associated with PPIs were less likely to occur in elderly patients (65-75: OR = 0.91 [0.87-0.95], p < 0.001; >75: OR = 0.93 [0.89-0.98], p < 0.01).

Conclusion: TAEs constitute a small but significant fraction of PPI-related AEs. This study highlights the need for cautious long-term use of PPIs and further research to understand the underlying mechanisms and risk factors. Clinicians should be aware of the potential tumor risks associated with prolonged PPI treatment.