Proton Pump Inhibitor Use and Risk of Gastric Cancer: Current Evidence from Epidemiological Studies and Critical Appraisal
Bibliographic record
Abstract
Proton pump inhibitors (PPIs) are used for maintaining or improving gastric problems. Evidence from observational studies indicates that PPI therapy is associated with an increased risk of gastric cancer. However, the evidence for PPIs increasing the risk of gastric cancer is still being debated. Therefore, we aimed to investigate whether long-term PPI use is associated with an increased risk of gastric cancer. We systematically searched the relevant literature in electronic databases, including PubMed, EMBASE, Scopus, and Web of Science. The search and collection of eligible studies was between 1 January 2000 and 1 July 2021. Two independent authors were responsible for the study selection process, and they considered only observational studies that compared the risk of gastric cancer with PPI treatment. We extracted relevant information from selected studies, and assessed the quality using the Newcastle−Ottawa scale (NOS). Finally, we calculated overall risk ratios (RRs) with 95% confidence intervals (CIs) of gastric cancer in the group receiving PPI therapy and the control group. Thirteen observational studies, comprising 10,557 gastric cancer participants, were included. Compared with patients who did not take PPIs, the pooled RR for developing gastric cancer in patients receiving PPIs was 1.80 (95% CI, 1.46−2.22, p < 0.001). The overall risk of gastric cancer also increased in patients with gastroesophageal reflux disease (GERD), H. pylori treatment, and various adjusted factors. The findings were also consistent across several sensitivity analyses. PPI use is associated with an increased risk of gastric cancer in patients compared with those with no PPI treatment. The findings of this updated study could be used in making clinical decisions between physicians and patients about the initiation and continuation of PPI therapy, especially in patients at high risk of gastric cancer. Additionally, large randomized controlled trials are needed to determine whether PPIs are associated with a higher risk of gastric cancer.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.019 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".