Iago Rodríguez-Lago
Gastroenterologist at the Inflammatory Bowel Disease Unit, Digestive System Department
Is the research of good quality?
"This study has a case-control design, in which patients diagnosed with a disease (in this case, gastric adenocarcinoma) are compared with others without that problem, while being similar or statistically adjusted for other factors such as age, sex, risk factors, etc., which provides an adequate and high-quality methodology for evaluating exposures (proton pump inhibitors in this example) that require a very long observation period.
In addition to this, data from health registries in five Nordic countries over a period of 26 years (1994-2020) have been included, which increases its external validity. On the other hand, by including more than 17,000 cancer patients and comparing them with more than 172,000 healthy individuals, together with access to detailed clinical information, the researchers were able to mitigate many of the weaknesses that affected previous research on this same topic.
How does it fit in with existing evidence?
"Historically, in recent decades, there has been doubt that drugs classified as antacids, and specifically proton pump inhibitors (omeprazole, esomeprazole, rabeprazole, etc.), could increase the risk of gastric cancer through increased gastrin, with recent meta-analyses estimating that this risk even doubled. However, these new findings clarify the situation by demonstrating that, once determining factors such as infection with the bacterium Helicobacter pylori, smoking, obesity and diabetes are adjusted for, the supposed association disappears. Therefore, these results do not support the hypothesis that long-term use of these drugs increases the risk of gastric cancer (specifically gastric adenocarcinoma), clarifying the uncertainty of previous studies.
What are the implications of this finding for clinical practice?
"For both healthcare professionals and patients, this finding is of great value and interest, as it provides reassurance and reaffirms the safety of long-term proton pump inhibitors, one of the most commonly prescribed drugs in Spain. By eliminating some of the doubts about this increased risk, the results facilitate clinical decision-making and (further) increase our confidence in these necessary treatments, often long-term, with a more solid evidence base."
Are there any important limitations to consider?
"Although the data are robust and have significantly improved on the limitations of previous studies, we must remember that this is an observational study, which means that it cannot establish a definitive cause-and-effect relationship. Furthermore, despite the researchers' efforts, there are factors that could not be measured, such as the patients' diet, their family history of stomach cancer, or the varying predisposition to this type of cancer in certain geographical areas, which, among other things, could influence the results. On the other hand, only the risk of gastric adenocarcinoma has been analysed, which, although it is the most common subtype, does not include all types of gastric cancer. Even so, the quality of the information obtained over more than two decades in several European countries offers one of the most reliable perspectives we have to date.