Acid Suppressing Therapies And Subsite-Specific Risk Of Stomach Cancer
E. Christina M. WENNERSTRÖM , Statens Serum Institut, Denmark
SIMONSEN J. 1
, CAMARGO M. 2
, RABKIN C. 2
, MELBYE M. 1,3
1 Statens Serum Institut, Department of Epidemiology Research, Copenhagen, Denmark
2 Division of Cancer, Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA
3 Department of Medicine, Stanford School of Medicine, Stanford, CA, USA
Purpose: Acid suppressive drugs are top prescribed medications worldwide. Previous studies have addressed associations of the two major classes, histamine type-2 receptor antagonists (H2RA) and proton-pump inhibitors (PPI), with risk of overall stomach cancer, with conflicting results. The main effects of these exposures are difficult to ascertain due to marked confounding by indication. As an alternative approach, this study investigated associations in the first decade of use of these drugs with incidence of stomach cancer by anatomic sub-site. We hypothesized that proximal extension of Helicobacter pylori infection resulting from acid suppression would disproportionately increase cancer risk at proximal non-cardia sub-sites.
Methods: 1.1 million individuals from the Danish Prescription Drug Registry exposed to any acid suppressing drugs between 1995 and 2011 (median 11.4 vs. 4.5 years for H2RAs and PPIs, respectively), matched by age, sex and municipality with up to 10 unexposed control persons using the Danish Civil Registration System. We used Cox proportional hazards modelling to calculate stomach cancer Hazard Ratios (HRs) and 95% confidence interval (CI).
Results: Sub-site-specific HRs for any exposure to H2RAs and PPIs were 3.7 (95% CI: 2.85-4.86) and 4.17 (95% CI: 3.50-4.98) for fundus/corpus as compared to 6.78 (95% CI: 5.23-8.80) and 6.26 (95% CI: 5.14-7.64) for antrum/pylorus, respectively. Restricted to individuals who filled five or more prescriptions, corresponding HRs were 4.06 (95% CI: 2.28-7.22) and 6.36 (95% CI: 4.93-8.20) for fundus/corpus vs. 8.01 (95% CI: 4.94-13.0) and 10.3 (95% CI: 7.68-13.7) for antrum/pylorus.
Conclusion: Moderate duration exposure to acid-suppressive drugs did not favour proximal localization of stomach cancer. These findings do not resolve a potential contribution to gastric carcinogenesis overall.
Funding source: The Intramural Research Program of the National Cancer Institute, National Institutes of Health, USA and the OAK foundation, supported this work.