Use of Proton Pump Inhibitor and Risk of Colorectal Cancer: A Meta-analysis of Observational Studies

BACKGROUND: Previous case-control studies have reported inconsistent findings regarding the association between proton pump inhibitor (PPI) use and colorectal cancer (CRC) risk. We investigated these associations using meta-analysis. METHODS: We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library in April 2011. Two evaluators independently reviewed and selected articles, based on pre-determined selection criteria. RESULTS: Out of 737 articles meeting our initial criteria, 5 case-control studies, which involved 120,091 participants (9,514 cases and 110,577 controls), were included in the final analyses. The overall use of PPI (used vs. never or rarely used) was not significantly associated with the risk of CRC in a fixed-effects model meta-analysis of all 5 case-control studies (odds ratio [OR], 1.08; 95% confidence interval [CI], 0.96 to 1.20; I(2) = 3.5%). Also, in sensitivity meta-analysis by cumulative duration of PPI use, there was no association between PPI use of 1 year or longer and the risk of colorectal cancer in a fixed-effects meta-analysis (OR, 1.09; 95% CI, 0.98 to 1.22; I(2) = 0%). CONCLUSION: Although hypergastrinemia could be an important factor in the pathogenesis of some colorectal cancers, our study suggests that this does not lead to significant clinical risk for most PPI users. Further prospective studies or randomized controlled trials related to PPI use and colorectal cancer risk are needed to investigate this association.