Proton pump inhibitors and the risk of colorectal cancer: a systematic review and meta-analysis of observational studies.

Abstract

The increased risk of colorectal cancer (CRC) associated with long-term use of proton pump inhibitors (PPIs) has attracted considerable attention; however, the conclusions of studies evaluating this correlation are inconsistent or even controversial. Therefore, we conducted a systematic review and meta-analysis to determine the association of PPI use with the risk of CRC. A systematic literature search was conducted in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials to identify relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for the associations between PPI use and the risk of CRC were estimated with a fixed-effects or random-effects model. We identified and included 9 observational studies (3 cohort studies and 6 case-control studies) comprising 1,036,438 participants. Overall, there was no statistically significant association between PPI use and the risk of CRC (pooled OR 1.26, 95% CI: 0.90-1.73; p = 0.166) when PPI exposure was assessed as a binary variable. However, a weak association between long-term use of PPIs and CRC was demonstrated (pooled OR 1.19, 95% CI: 1.09-1.31; p < 0.001) when the cumulative duration of PPI exposure was confined to > 5 years. Although the present meta-analysis suggests a weak association between long-term use (> 5 years) of PPIs and CRC, there is not enough statistical power to refute or confirm an association between the use of PPIs and CRC. More high-quality prospective cohort studies are needed to assess this correlation.