Proton pump inhibitors and risk of gastrointestinal cancer: A meta-analysis of cohort studies

Although proton pump inhibitors (PPIs) are widely used in the treatment of various acid-related disorders, observational studies have raised concern about an association between PPI use and the risk of gastrointestinal cancer. The present study aimed to investigate the association between them using a meta-analysis of cohort studies. PubMed and Excerpta Medica dataBASE were searched from inception to December 2022 to identify relevant cohort studies. The primary outcome was the risk of gastrointestinal cancer among PPI users, expressed as a pooled odds ratio (OR), relative risk (RR) or hazard ratio (HR) and its 95% CI based on a random-effects model. A total of 25 cohort studies from 23 articles were included in the final analysis. In the meta-analysis of all studies, an increased risk of gastrointestinal cancer following the use of PPIs was observed (OR/RR/HR, 2.09; 95% CI, 1.78-2.46). Subgroup analyses by type of cancer also revealed an association between PPI use and the risk of esophageal, gastric, liver and pancreatic cancer, whereas there was no association for colorectal cancer. The increased risk of gastrointestinal cancer was also observed in individuals who had used PPIs for <1 year (OR/RR/HR, 5.23; 95% CI, 2.96-9.24) as well as individuals who had used PPIs for up to 3 years. The present meta-analysis revealed that the use of PPIs was associated with an increased risk of gastrointestinal cancer.