Use of Acid-Suppressant Medications After Diagnosis Increases Mortality in a Subset of Gastrointestinal Cancer Patients

  • Sanjana Ayyagari
  • Mimi C. Tan
  • Yan Liu
  • Hashem B. El-Serag
  • Aaron P. ThriftEmail author
Original Article



Acid-suppressant medications, including proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs), are frequently prescribed and have been linked to increased risk of some gastrointestinal cancers.


We examined whether post-diagnosis use of PPIs/H2RAs is associated with the risk of mortality in gastrointestinal cancer patients.


We used data from patients with esophageal cancer, gastric cancer, or hepatocellular carcinomas (HCCs) in the national VA Central Cancer Registry diagnosed between 2002 and 2016. We identified PPI/H2RA prescriptions that were filled before and after cancer diagnosis and used time-dependent Cox regression models to calculate adjusted hazard ratios (HRs) and 95% CIs for mortality risk. We used a time-varying exposure to avoid immortal-time bias and a 3-month lag to reduce reverse causation. A sensitivity analysis was conducted varying the lag duration between the date of cancer diagnosis and the start of follow-up.


PPIs were used by the majority (54% post-diagnosis use) of patients. We found no association between post-diagnosis PPI use and cancer-specific mortality in esophageal adenocarcinoma (HR 0.93; 95% CI 0.84–1.02), esophageal squamous cell carcinoma (HR 0.99; 95% CI 0.87–1.12), or gastric cardia cancer (HR 1.04; 95% CI 0.89–1.22) patients. Post-diagnosis PPI use was, however, associated with the increased risk of cancer-specific mortality for patients with gastric non-cardia cancer (HR 1.50; 95% CI 1.29–1.74) and HCC (HR 1.31; 95% CI 1.23–1.40). The results were similar for associations with post-diagnosis use of H2RAs. There was no association with pre-diagnosis PPI/H2RA use.


Post-diagnosis PPI/H2RA use was associated with the increased mortality in gastric non-cardia cancer and HCC patients.


Cancer Mortality Prognosis Acid-suppressant medication use 


Author’s contribution

APT was involved in study concept and design. APT and YL performed statistical analysis and interpretation of data. HES and APT were involved in acquisition of data and obtained funding. YL prepared the data. SA, MCT, HES, and APT drafted the manuscript. SA, MCT, YL, HES, and APT were involved in critical review of the manuscript for important intellectual content. All authors read and approved the final version for submission.

Financial support

This work was supported in part by National Institutes of Health grant P30 DK056338 (Study Design and Clinical Research Core), which supports the Texas Medical Center Digestive Diseases Center. This research was supported in part with resources at the VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (#CIN 13-413), at the Michael E. DeBakey VA Medical Center, Houston, TX. The opinions expressed reflect those of the authors and not necessarily those of the Department of Veterans Affairs, the United States government or Baylor College of Medicine.

Compliance with Ethical Standards

Conflict of interests


Supplementary material

10620_2019_5984_MOESM1_ESM.docx (21 kb)
Supplementary material 1 (DOCX 21 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Section of Epidemiology and Population Sciences, Department of MedicineBaylor College of MedicineHoustonUSA
  2. 2.Section of Gastroenterology and Hepatology, Department of MedicineBaylor College of MedicineHoustonUSA
  3. 3.Center for Innovations in Quality, Effectiveness and Safety (IQuESt)Michael E DeBakey Veterans Affairs Medical CenterHoustonUSA
  4. 4.Dan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonUSA

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