Reacción a "Study claims use of drugs such as omeprazole is not associated with an increased risk of a type of gastric cancer, contrary to previous studies"

The article by Duru et al. contrasts sharply with the results provided in numerous previous clinical studies and meta-analyses over the last 40 years, which suggested an increased risk (in some cases twice as high) of gastric cancer associated with the use of drugs in the proton pump inhibitor (PPI) family, such as omeprazole. These authors point out that, in many cases, these positive associations could be explained by relevant methodological limitations, such as protopathic bias, the inclusion of patients using the drug for a short period of time, the lack of differentiation between cardia cancer and other gastric cancers, or the lack of adjustments in cases of infection by the bacterium Helicobacter pylori, whose relationship with gastric cancer is well established. In fact, sensitivity analyses performed in this study reproduce increases in risk when these limitations are reintroduced, supporting the hypothesis that much of the previous evidence may reflect spurious associations rather than a real causal effect.

Despite being a prospective multicentre case-control study, from a methodological point of view, it is worth highlighting the use of comprehensive national health registries from five Nordic countries with a strong track record in this area (Denmark, Finland, Iceland, Norway and Sweden) and the inclusion of more than 17,232 cases of gastric adenocarcinoma (not cardia cancer) and more than 172,297 controls, followed over a period of 26 years, which gives the study great statistical power and precision in its estimates. In addition, the linking of subjects by personal identifiers and the absence of missing data significantly reduce the risk of classic biases such as selection or recall bias, which are common in smaller-scale observational studies. The explicit exclusion of exposure to medication in the 12 months prior to diagnosis and the adjustment for multiple key factors, such as age, gender, treatment for Helicobacter pylori eradication, history of peptic ulcer or type 2 diabetes, tobacco and alcohol consumption, obesity, or consumption of certain medications, also reinforce the internal validity of the study.

From a clinical practice perspective, the findings provide reassuring results. In patients with a clear indication for prolonged treatment with PPIs (and histamine type 2 receptor antagonists), especially in cases of gastroesophageal reflux, these results suggest that there would be no increased risk of gastric adenocarcinoma (not cardia cancer) attributable to this type of drug, which may contribute to more balanced and evidence-based decision-making, reducing unfounded fears in both patients and healthcare professionals. However, the authors rightly point out that prolonged use of PPIs still requires periodic reassessment for other known adverse effects, although these are not related to gastric neoplasms.

Although the study is robust, it is not without limitations. Its case-control design, even though based on extensive prospective registries, does not allow causality to be established definitively. Furthermore, detailed information is not available on some potentially relevant factors, such as diet (e.g., salt intake), family genetic history, or other clinical variables related to the severity of gastric pathology. It should also be mentioned that the study is based on Nordic populations, which could partially limit its extrapolation to regions with different epidemiological profiles for gastric cancer. Even so, these limitations do not seem sufficient to invalidate the main conclusion of the study.

In conclusion, this study represents a significant contribution to the debate on the long-term safety of PPIs, demonstrating that, when biases and other confounding factors are adequately controlled, the previously described association with gastric cancer does not appear to hold. Furthermore, its methodological rigour makes it an important reference for critically reinterpreting the previous literature and guiding clinical practice based on more solid evidence.