The long-term use of a proton pump inhibitor (PPI) does not appear to be associated with an increased risk of gastric cancer, an analysis has concluded.
Fears that use of PPIs could lead to gastric cancer have been ongoing for decades, the researchers noted in the BMJ, adding that a randomised controlled trial would not be feasible.
While three recent studies had found as much as a two-fold increased risk, they were hampered by ‘methodological limitations’ making the true picture unclear.
This population-based, case-control study used prospectively collected data over a 26-year period from multiple complete nationwide registries in five Nordic nations: Denmark, Finland, Iceland, Norway, and Sweden.
The researchers compared more than 17,000 cases of gastric cancer with 172,000 controls, looking at the use of PPIs for more than a year, as well as histamine-2-receptor antagonists (H2RAs).
‘Potentially false association’ between PPIs and gastric cancer
They carefully excluded medication use from the 12 months before the gastric cancer diagnosis date, or study inclusion date for the control group, to prevent the reporting of a potentially false association, the researchers explained.
Other confounding factors were accounted for including age, sex, Helicobacter pylori eradication treatment, peptic ulcer disease, smoking and alcohol related diseases, obesity or type 2 diabetes, and some other medications.
When all this was taken into account, there was no remaining association between long term use of PPIs or H2RAs and increased risk of gastric cancer, they concluded.
Clinical implications
The team at the Karolinska Institute in Sweden said the previous studies could have been skewed by including PPI use shortly before diagnosis, focusing on short-term prescribing or failing to account for other variables.
‘The results of this study do not support the hypothesis that long term PPI use is associated with an increased risk of gastric adenocarcinoma,’ they said. ‘This finding should offer relief for patients needing long term proton pump inhibitor therapy and is valuable for healthcare in clinical decision making.’
But they added that long term PPI use may cause side effects and increase the risk of some other potentially serious conditions such as Clostridium difficile-associated diarrhoea, osteoporosis, and vitamin or electrolyte malabsorption.
A version of this article was originally published by our sister publication Pulse.
