Journal
BRITISH JOURNAL OF CANCER
Volume 100, Issue 9, Pages 1503-1507Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6605024
Keywords
stomach neoplasms; proton pump inhibitors; histamine-2-antagonists; risk; cohort study
Categories
Funding
- International Epidemiology Institute (IEI)
- Clinical Epidemiological Research Foundation
- Western Danish Research Forum for Health Sciences
- Karen Elise Jensen Foundation
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Proton pump inhibitor (PPI) use leads to hypergastrinaemia, which has been associated with gastrointestinal neoplasia. We evaluated the association between PPI use and risk of gastric cancer using population-based health-care registers in North Jutland, Denmark, during 1990-2003. We compared incidence rates among new users of PPI (n = 18 790) or histamine-2-antagonists (H2RAs) (n = 17478) and non-users of either drug. Poisson regression analysis was used to estimate incidence rate ratios (IRRs) adjusted for multiple confounders. We incorporated a 1-year lag time to address potential reverse causation. We identified 109 gastric cancer cases among PPI users and 52 cases among H2RA users. After incorporating the 1-year lag time, we observed IRRs for gastric cancer of 1.2 (95% CI: 0.8-2.0) among PPI users and 1.2 (95% CI: 0.8-1.8) among H2RA users compared with non-users. These estimates are in contrast to significant overall IRRs of 9.0 and 2.8, respectively, without the lag time. In lag time analyses, increased IRRs were observed among PPI users with the largest number of prescriptions or the longest follow-up compared with H2RA users or non-users. Although our results point to a major influence of reverse causation and confounding by indication on the association between PPI use and gastric cancer incidence, the finding of increased incidence among PPI users with most prescriptions and longest follow-up warrants further investigation.
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