For people who rely on long-term acid-reducing medications, a large new study offers reassurance. Researchers found no evidence that extended use of proton pump inhibitors, or PPIs, is linked to a higher risk of stomach cancer.
The study, published in The BMJ, analyzed health registry data from Denmark, Finland, Iceland, Norway and Sweden over a 26-year period. Together, the countries provide some of the most comprehensive population-level health data in the world.
PPIs are widely prescribed to treat conditions such as acid reflux, ulcers and gastrointestinal bleeding. Concerns about a possible cancer risk have circulated for decades, fueled by earlier studies that suggested a potential association but were limited by methodological challenges.
To address those concerns, researchers designed a large population-based case-control study that carefully accounted for many of the factors that can complicate cancer risk research.
They identified 17,232 people diagnosed with stomach cancer and matched each case with 10 individuals of the same age, sex, country and calendar year who did not have cancer. That produced a comparison group of more than 172,000 people.
The researchers examined long-term use of PPIs and another class of acid-reducing drugs, histamine-2 receptor antagonists, defined as use lasting more than one year. To reduce the risk of false associations, they excluded drug use in the year immediately before a cancer diagnosis.
They also adjusted for factors known to influence stomach cancer risk, including treatment for Helicobacter pylori infection, peptic ulcer disease, smoking- and alcohol-related conditions, obesity, type 2 diabetes and use of other medications.
After accounting for those factors, the analysis found no remaining association between long-term use of either type of acid-reducing drug and stomach cancer.
“The results of this study do not support the hypothesis that long-term proton pump inhibitor use is associated with an increased risk of gastric adenocarcinoma,” the authors wrote.
The researchers emphasized that their findings should help guide clinical decision-making, particularly for patients who need PPIs for chronic conditions.
“This finding should offer relief for patients needing long-term proton pump inhibitor therapy and is valuable for healthcare in clinical decision making,” they added.
As with all observational studies, the researchers noted limitations. They could not fully account for factors such as diet or family history of stomach cancer, and the study cannot establish cause and effect. Still, they said the size of the population, the long follow-up period and the quality of the registry data helped address many of the weaknesses seen in earlier research.
This research was supported by public and nonprofit research organizations in Sweden and the Nordic region, including the Swedish Research Council, the Nordic Cancer Union and the Swedish Cancer Society.