Statins and the Risk of Esophageal Cancer: A Systematic Review and Meta-analysis: ACG/AstraZeneca Fellow Award
Bibliographic record
Abstract
Purpose: Esophageal cancer (EC) is a lethal cancer with increasing incidence in the United States, especially esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). Several preclinical and observational studies have shown that statins may have chemo-preventive effects on EC. We performed a systematic review with meta-analysis of clinical studies evaluating the effect of statin use on the risk of EC, in particular on the development of EAC or progression of dysplasia in patients with BE. Methods: We conducted a systematic search of Medline, Embase and Web of Science (from inception up to May 2012), and manually reviewed the bibliographies of relevant articles. Studies were included if they (1) evaluated and clearly defined exposure to statins, (2) reported EC outcomes, and (3) reported relative risks (RR) or odds ratio (OR) or provided data for their estimation. Summary OR estimates, maximally adjusted for potential confounders, with 95% confidence intervals (CIs) were calculated using the random-effects model. Results: Eleven studies (6 case-control, 5 cohort) reporting 8,613 cases of EC in 995,687 patients were included in the analysis. Meta-analysis of these studies showed a significant 30% reduction in EC incidence with statin use (adjusted OR 0.70, 95% CI 0.57-0.86), though there was considerable heterogeneity, attributable partly to method of ascertainment of exposure to statins. On restricting analysis to 7 high-quality observational studies (Newcastle-Ottawa score >7), use of statins continued to show a significant protective effect against development of EC (adjusted OR =0.70, 95% CI 0.56-0.88, Cochran's Q p=0.13, I2 =40). In analyzing a subset of patients with known BE (5 studies, 312 EAC in 2,125 patients), statin use was associated with a significant 41% decrease in the risk of EAC, after adjusting for potential confounders (adjusted OR 0.59, 95% CI 0.45-0.78) with results being consistent across all studies. The number needed to treat with statins to prevent 1 case of EAC in patients with BE was 389. Longer duration of statin use (adjusted OR =0.44, 95% CI 0.24-0.78), and combined use of statins and non-steroidal anti-inflammatory medications/aspirin (adjusted OR =0.28, 95% CI 0.14-0.56) had a greater protective effect. Table 1 shows the results of subgroup analysis.Table: [25] Subgroup analysisConclusion: Meta-analysis of existing observational studies support a protective association between statin use and EC, especially in patients with BE. Given the high mortality rates after a diagnosis of EAC, these results support chemoprevention trials evaluating statins in populations at high risk of developing EAC.
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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 | 0.014 | 0.033 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.011 | 0.024 |
| Bibliometrics | 0.006 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".