Nordic Gastric and Esophageal Tumor Study

This is a population-based case-control study in all 5 Nordic countries from 1994 onwards. All cases with an esophageal or gastric tumor will be compared with 10 times as many population controls, frequency-matched by age, sex, and calendar year, country. This design offers excellent statistical power, length and completeness of follow-up, quality of data on exposures, outcomes and confounders, and control for confounding.The project will include a specific study entitled "Long-term medication with proton pump inhibitors and risk of gastric cancer", which is summarized here:Research question: Medication with proton pump inhibitors (PPI) (e.g., omeprazole and esomeprazole) is one of the most common long-term therapies globally, prompted by its high anti-acidic efficacy and good short-term safety profile. Gastric cancer is the 3rd leading cause of cancer-related mortality globally, responsible for 770,000 deaths each year. There are clear biological mechanisms linking long-term PPI-use with an increased risk of gastric cancer. However, existing research has not been able to provide a definite answer to whether long-term PPI-use is associated with an increased risk of gastric cancer. The reasons are that the literature is hampered by too short follow-up time to assess cancer development, and also insufficient statistical power, lack of population-based design and confounding.With the availability of nationwide complete medication registries in the Nordic countries, the firsts two starting already in 1994 (Denmark and Finland), we can now, by adding registry data from all Nordic countries together, conduct the first study providing a robust and valid answer to this research question.Overarching aim This project aims to clarify if (and if so to what extent) long-term PPI-therapy influences the risk of developing gastric adenocarcinoma.For validation reasons, we will also examine how long-term use of histamine-2-receptor blockers (H2RB) influences the risk of developing gastric adenocarcinoma. These analyses will validate that the findings are specific for PPIs. H2RB are used for the same indications as PPIs, but with a different biological mechanism.Hypothesis We plan to test the hypothesis that long-term use of PPI (but not H2RB) increases the risk of gastric adenocarcinoma.PrerequisitesThis will be the first project with all prerequisites to provide conclusive answers to the hypotheses above, i.e.:Long follow-up (up to 28 years)Complete follow-up (by virtue of the nationwide complete Nordic registries)Population-based design (which rules out biased selection of cases or controls)Superior statistical power (all five Nordic countries participate with nationwide data)High-quality data on exposures, outcomes and confounders (thanks to well-maintained and complete nationwide Nordic health data registries)Control for confounding factors (available for all participants, both cases and controls)

Inclusion Criteria:Diagnosis of esophageal or gastric tumor or frequency matched population control participantsExclusion Criteria:Age below 18 years