Long-term medication with proton pump inhibitors and risk of gastric cancer

AimsTo clarify if long-term proton pump inhibitor (PPI) medication increases risk of developing gastric cancer. BackgroundPPI-use is very common, but long-term use might cause gastric cancer. Gastric cancer is linked with Helicobacter pylori-infection and is one of the most common and deadly tumours globally.

The literature examining PPI-use in relation to risk of gastric cancer has had too short follow-up, too low statistical power and too much problems with bias by selection and confounding to provide conclusive results. MethodsWe will conduct a population-based case-control study in all 5 Nordic countries in 1994-2022.

The drug registries allow assessment of long-term PPI-use. 47,000 cases with gastric cancer will be compared with 10 times as many (470,000) population controls, matched by confounding variables.

This project offers excellent statistical power, length and completeness of follow-up, and quality of data on exposures, outcomes and confounders. The work will be completed within 3-years.

SignificanceThis planned project is the first with all prerequisites to provide a robust and valid answer to the question if long-term PPI-use increases the risk of gastric cancer.

The results may lead to clinical actions, e.g., avoidance of PPI-use in patients with heredity for gastric cancer, endoscopic surveillance in patients at an increased risk of gastric cancer who still need PPI-therapy, and test for and eradicate Helicobacter pylori in patients who need PPI.