Proton pump inhibitor use and cancer mortality. Issue 6 (2nd May 2018)

• Record Type: Journal Article
• Authors: Tvingsholm, Siri A.; Dehlendorff, Christian; Østerlind, Kell; Friis, Søren; Jäättelä, Marja
• Is Part Of: International journal of cancer. Volume 143:Issue 6(2018)
• Page Start: 1315
• Page End: 1326
• Publication Date: 2018-05-02
• Subjects: proton pump inhibitors -- pharmacoepidemiology -- mortality -- tumor immunity -- murine cancer model; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31529
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Proton pump inhibitors (PPIs) are commonly used as a supplement to cancer therapy. Yet, their effect on cancer mortality is largely unknown. Using data from Danish nationwide registries and Cox models regressing of both propensity scores and drug use, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for cancer‐specific and noncancer death among PPI users (≥2 prescriptions within six months after diagnosis; n = 36, 066) compared with nonusers (<2 prescriptions, n = 311, 853) or users of histamine H2 ‐receptor antagonists (H2 RA; n = 5, 152). Adjusted HRs for cancer‐specific mortality among postdiagnostic PPI users as compared with nonusers or H2 RA users were 1.29 (95% CI, 1.27–1.32) and 1.15 (95% CI, 1.10–1.20), respectively. HRs for cancer mortality associated with PPI use were highest for ovarian (1.35; 95% CI, 1.20–1.52) and lowest for esophageal cancer (0.91; 95% CI, 0.81–1.04). The associations were stronger among new PPI users after cancer diagnosis, indicating potential confounding. To test the effect of PPIs on tumor growth in a model system free for confounding factors, we investigated the effect of pantoprazole on tumor growth in mice. Pantoprazole (5 mg/kg/day) enhanced tumor growth ( p = 0.033) and reduced the antitumor activity of gemcitabine ( p = 0.008) in fibrosarcoma‐bearing Balb/c mice, but not in immunodeficient Balb/c nude mice. In breast carcinoma‐bearing FVB/N mice, pantoprazole had no effect on tumor growth alone but it reduced the life‐prolonging effect of doxorubicin significantly ( p = 0.007). Taken together, these data raise concerns about the increasing use of PPIs and calls for further studies addressing their safety among cancer patients. Abstract : What's new? Due to the importance of acidic microenvironment for cancer progression, proton pump inhibitors (PPIs), which are commonly prescribed for treating gastroesophageal reflux and peptic ulcer, are also increasingly used as a supplement to cancer therapy. Yet, their effect on cancer mortality is largely unknown. This large retrospective cohort study among Danish cancer patients found a association between postdiagnostic use of PPIs and increased cancer mortality. Furthermore, PPI‐induced acceleration of tumor growth was observed in mouse models. These data raise concerns about the increasing use of PPIs and calls for further studies addressing their safety among cancer patients, in particular.