Relationship between antacids and stomach cancer risk

Long-term use of proton pump inhibitors (PPIs)a class of medications widely used to treat acid reflux and ulcersmay not be linked to an increased risk of developing gastric (stomach) cancer, a study of Nordic health data published by the Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden, finds. The BMJ.

This finding should offer relief to patients who need long-term PPI therapy and is valuable for clinical decision making in healthcare settings, the researchers say.

Fears that proton pump inhibitors could cause stomach cancer have existed since the 1980s. Recent research has linked their use to a risk approximately twice as highbut 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, researchers designed a study that made extensive efforts to avoid and evaluate these prior weaknesses.

Their findings are based on data from health care records in the five nordic countries (Denmark, Finland, Iceland, Norway and Sweden) over a period of 26 years, from 1994 to 2020.

They identified 17,232 patients with stomach cancer (cases) and randomly compared each of them by age, sex, calendar year and country with 10 healthy participants (controls) of the entire population of each country: a total of 172,297.

They then recorded long-term use (more than 1 year) of proton pump inhibitors and histamine-2 receptor antagonists (another class of medications used to reduce stomach acid), excluding the 12 months before the date of diagnosis (cases) or the date of study inclusion (controls) to avoid reporting a potentially spurious association.

They were also taken into account other factors that could have influenced the results, such as age, sex, treatment for the eradication of Helicobacter pylori (the bacteria involved in the development of stomach cancer), peptic ulcer, diseases related to smoking and alcohol, obesity or type 2 diabetesand the 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 an increased risk of stomach cancer.

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

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

Therefore, they conclude: “The results of this study do not support the hypothesis that long-term use of proton pump inhibitors is associated with an increased risk of gastric adenocarcinoma.” “This finding should offer relief to patients who need long-term proton pump inhibitor therapy and is valuable for healthcare in clinical decision making,” they add.