Observational studies suggest that nonsteroidal anti-inflammatory drugs (
NSAIDs) reduce the risk of esophageal
adenocarcinoma, but it is not known at what stage they may act in the esophageal
inflammation-
metaplasia-
adenocarcinoma sequence. In an all-Ireland case-control study, we investigated the relationship between the use of
NSAIDs and risk of
reflux esophagitis,
Barrett's esophagus, and esophageal
adenocarcinoma. Patients with esophageal
adenocarcinoma, long-segment
Barrett's esophagus and population controls were recruited from throughout Ireland.
Esophagitis patients were recruited from Northern Ireland only. Data were collected on known and potential risk factors for esophageal
adenocarcinoma and on the use of
NSAIDs, including
aspirin, at least 1 year before interview. Associations between use of
NSAIDs and the stages of the esophageal
inflammation-
metaplasia-
adenocarcinoma sequence were estimated by multiple logistic regression. In total, 230
reflux esophagitis, 224
Barrett's esophagus, and 227 esophageal
adenocarcinoma and 260 population controls were recruited. Use of
aspirin and
NSAIDs was associated with a reduced risk of
Barrett's esophagus [odds ratio [OR; 95% confidence interval (95% CI)], 0.53 (0.31-0.90) and 0.40 (0.19-0.81), respectively] and esophageal
adenocarcinoma [OR (95% CI), 0.57 (0.36-0.93) and 0.58 (0.31-1.08), respectively].
Barrett's esophagus and esophageal
adenocarcinoma patients were less likely than controls to have used
NSAIDs. Selection or recall bias may explain these results and the results of previous observational studies indicating a protective effect of
NSAIDs against esophageal
adenocarcinoma. If
NSAIDs have a true protective effect on the esophageal
inflammation-
metaplasia-
adenocarcinoma sequence, they may act early in the sequence.