To Örebro University

Background: Proton pump inhibitors (PPIs) are associated with microbiome changes of the gut, which in turn may affect the progression of colorectal cancer (CRC). This study aims to assess the associations between PPI use and all-cause and CRC-specific mortality.

Methods: We selected all patients registered in the Swedish Prescribed Drug Registry who were diagnosed with CRC between 2006 and 2012 (N = 32,411, 54.9% PPI users) and subsequently followed them through register linkage to the Swedish Causes of Death Registry until December 2013. PPI users were patients with >= 1 post-diagnosis PPI dispensation. Time-dependent Cox-regression models were performed with PPI use as time-varying exposure.

Results: Overall 4746 (14.0%) patients died, with an aHR of 1.38 (95% CI 1.32-1.44) for all-cause mortality comparing PPI users with PPI nonusers. Higher-magnitude associations were observed among male, cancer stage 0-I, rectal cancer and patients receiving CRC surgery. The PPI-all-cause mortality association was also more pronounced comparing new users to non-users (aHR = 1.47, 95%CI 1.40-1.55) than comparing continuous users to non-users (aHR = 1.32, 95%CI 1.24-1.39). The risk estimates for CRC-specific mortality comparing PPI users to PPI nonusers were similar to those for all-cause mortality.

Conclusion: PPI use after the CRC diagnosis was associated with increased all-cause and CRC-specific mortality.