Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis.
OBJECTIVE
Esophageal carcinomas have high fatality rates, making chemoprevention agents desirable. We performed a systematic review with meta-analysis of observational studies evaluating the association of aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and esophageal cancer.


METHODS
We evaluated the MEDLINE, BIOSIS, and Web of Science electronic databases (1980-2001); manually reviewed the literature; and consulted with experts. Studies were included if they: (1) evaluated exposure to NSAIDs, aspirin, or both; (2) evaluated esophageal cancer; and (3) reported relative risks or odds ratios or provided data for their calculation. Data were independently abstracted by 2 investigators. The primary and sensitivity analyses used both fixed and random-effects models.


RESULTS
Nine studies (2 cohort, 7 case control) containing 1813 cancer cases were identified. All primary summary estimates were homogeneous. Statistical pooling showed a protective association between any use of aspirin/NSAID and esophageal cancer (odds ratio [OR] = 0.57; 95% confidence interval [CI], 0.47-0.71). Both intermittent (OR = 0.82; CI, 0.67-0.99) and frequent medication use were protective (OR = 0.54; CI, 0.43-0.67), with greater protection with more frequent use. Stratified by medication type, aspirin use was protective (OR = 0.5; CI, 0.38-0.66), and NSAIDs had a borderline protective association (OR = 0.75; CI, 0.54-1.0). Any use was protective against both esophageal adenocarcinoma (OR = 0.67; CI, 0.51-0.87) and squamous cell carcinoma (OR = 0.58; CI, 0.43-0.78).


CONCLUSIONS
Pooled results support a protective association between aspirin and NSAIDs and esophageal cancer (of both histological types) and provide evidence for a dose effect. These findings support evaluating these agents in clinical trials of high-risk patients.
Corley
Douglas A
DA
Northern California Kaiser Division of Research, Department of Medicine, University of California-San Francisco, 2238 Geary Boulevard, GI 2-West, San Francisco, CA 94115, USA. corley@itsa.ucsf.edu
Kerlikowske
Karla
K
Verma
Rajiv
R
Buffler
Patricia
P
D000230:Adenocarcinoma / Q000517:prevention & control*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000517:prevention & control*; D006801:Humans
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin