Long term proton pump inhibitor use may not be associated with an increased risk of gastric adenocarcinoma

The long-term use of proton pump inhibitors (PPIs), a class of drugs widely used to treat acid reflux and ulcers, may not be linked to any increased risk of developing gastric adenocarcinoma, according to a study of Nordic health data.

"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 researchers noted. “This finding should offer relief for patients needing long-term proton pump inhibitor therapy and is valuable for health care in clinical decision-making.”

A fear that proton pump inhibitors could lead to stomach cancer has been ongoing since the 1980s. Recent research has linked their use to around a twofold increased risk, but the literature is hampered by several methodological limitations, making this possible association uncertain.

To help clarify whether long-term use of proton pump inhibitors is associated with an increased risk of stomach cancer, the researchers designed a study that made extensive efforts to avoid and assess these previous weaknesses. Their findings are based on health care registry data in the five Nordic countries - Denmark, Finland, Iceland, Norway and Sweden - over a 26-year period from 1994 to 2020.

They identified 17,232 patients with stomach cancer (cases) and randomly matched each one by age, sex, calendar year, and country with 10 healthy participants (controls) from each country's entire population - a total of 172,297.

They then recorded long-term (more than one year) use of proton pump inhibitors and histamine-2-receptor antagonists (another class of drugs used to reduce stomach acid) excluding the 12 months before the diagnosis date (cases) or study inclusion date (controls) to prevent the reporting of a potentially false association.

Other factors that may have influenced the results were also accounted for. These included age, sex, Helicobacter pylori eradication, peptic ulcer disease, smoking and alcohol-related diseases, obesity or type 2 diabetes, and use of certain medications.

After adjusting for these factors, the researchers found no remaining association between long-term use of proton pump inhibitors or histamine-2-receptor antagonists and increased risk of stomach cancer.

This is an observational study, so no firm conclusions can be drawn about cause and effect. In addition, despite extensive efforts, the authors could not rule out the possibility that unmeasured factors, such as diet and family history of stomach cancer, may have affected the results.

However, they noted that this multinational study based on up to 26 years of high-quality registry data allowed them to mitigate many of the biases and other problems affecting previous research on this topic.

The findings were featured in the paper, ‘Long term use of proton pump inhibitors and risk of stomach cancer: population based case-control study in five Nordic countries’, published in The British Medical Journal. To access this paper, please click here