Proton Pump Inhibitor Use and Risk of Gastric, Colorectal, Liver, and Pancreatic Cancers in a Community-Based Population.

INTRODUCTION Proton pump inhibitors (PPIs) are commonly used for gastrointestinal disorders; given they increase the systemic levels of gastrin, a trophic hormone, there is a concern about their carcinogenicity. This study evaluated the associations PPI use and the risks of gastrointestinal cancers compared with the users. METHODS We performed a nested case-control study in a large, community-based integrated healthcare setting. Cases were adults with gastric (n = 1,233), colorectal (n = 18,595), liver (n = 2,329), or pancreatic cancers (n = 567). Each case was matched with up to 10 controls by age, sex, race/ethnicity, medical facility, and enrollment duration. The primary exposure was defined as ≥2-year cumulative PPI supply. Data were obtained from pharmacy, cancer registry, and electronic medical record databases. Associations were evaluated using conditional logistic regression and adjusted for multiple confounders. We also evaluated the cancer risks separately by PPI dose, duration of use, and dose and duration. RESULTS PPI use of ≥2-years was not associated with the risks of gastric (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 0.81-1.42), colorectal (OR: 1.05, 95% CI: 0.99-1.12), liver (OR: 1.14, 95% CI: 0.91-1.43), or pancreatic cancers (OR: 1.22, 95% CI: 0.89-1.67), compared with the users. In exploratory analyses, elevated cancer risks were primarily restricted to those with ≥10 years of PPI use, but no consistent associations were found for increasing PPI dose and/or duration of use. DISCUSSION PPI use of ≥2 years was not associated with increased risks of gastrointestinal cancers. The cancer risks associated with PPI use of ≥10 years were further studied.