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

purposeThe 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.

methodsA 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.

resultsWe 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.

conclusionsAlthough 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.