Meta‐analysis: Use of proton pump inhibitors and risk of gastric cancer in patients requiring gastric acid suppression
Bibliographic record
Abstract
Summary Background Proton‐pump inhibitors (PPIs) are suspected to increase the risk of gastric cancer. Aim To assess the risk of gastric cancer associated with the use of PPIs. Methods We systematically searched Medline/PubMed, Embase and Scopus databases (until June 1, 2022) for randomised and non‐randomised studies (NRS) of the association between PPIs and gastric cancer having considered Histamine‐2 receptor antagonists (H2RAs) users as controls. We chose this comparison to minimise confounding by indication, and focus on patients requiring gastric acid suppression. Two authors independently extracted study data and assessed each study's risk of bias. Maximally‐adjusted relative risk (RR) estimates were extracted. Heterogeneity and small‐study effect were examined, and summary estimates were calculated using random‐ and fixed‐effect models. Stratified analyses and meta‐regression were employed to explore heterogeneity. We used GRADE to evaluate the certainty of evidence. Results Of 8375 records, 12 NRS (>6 million patients; 11,554 gastric cancers) and two randomised clinical trials (498 patients; 1 gastric cancer) fulfilled the eligibility criteria. Randomised evidence was very imprecise and provided very‐low certainty evidence. Meta‐analysis of six NRS providing a comprehensive adjustment for confounding (2.5 million patients; 7372 gastric cancers) did not show any association between PPIs and gastric cancer (RRrandom = 1.07, 0.97–1.19; RRfixed = 1.05, 0.98–1.12). The certainty of the evidence was low. No convincing evidence of dose–response, or increased risk with long‐term use, was found. Lack of or minimal adjustment for confounding was associated with larger effect sizes. Conclusions We found no association between PPIs and gastric cancer in NRS having adequately controlled for confounding. Published studies may suffer residual confounding. Systematic review registration: CRD42022335971.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.029 | 0.052 |
| Meta-epidemiology (narrow) | 0.004 | 0.002 |
| Meta-epidemiology (broad) | 0.020 | 0.073 |
| Bibliometrics | 0.008 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.005 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 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 source (direct Gemma or distilled Codex), 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".