Nonsteroidal anti-inflammatory drugs and esophageal inflammation - Barrett's esophagus - adenocarcinoma sequence: a meta-analysis

The incidence of esophageal adenocarcinoma has markedly increased in the last few decades and Barrett's esophagus is regarded as the precursor lesion of this cancer. The aim of the study was to quantify the adenocarcinoma risk associated with nonsteroidal anti-inflammatory drug use and to determine at which stage chemoprevention with this drug is the most effective in esophageal inflammation – Barrett's esophagus – adenocarcinoma sequence. A literature search was performed to identify studies published between 1998 and 2009 for relevant risk estimates. Fixed and random effect meta-analytical techniques were conducted for aspirin, nonaspirin nonsteroidal anti-inflammatory drugs, and all nonsteroidal anti-inflammatory drugs. Four cohort and 10 case-control studies were included. Use of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs in normal population was associated with a reduced risk of adenocarcinoma (odds ratio [OR]: 0.73, 95% confidence interval [CI]: 0.65–0.83; OR: 0.84, 95% CI: 0.72–0.98, respectively). The use of all nonsteroidal anti-inflammatory drugs was associated with a reduced risk of adenocarcinoma (relative risk [RR]: 0.64, 95% CI: 0.42–0.96) in Barrett's esophagus patients. However, no obvious dose-effect relationships were found. In addition, we discovered a reverse association between drugs use and adenocarcinoma risk in people without a history of upper gastrointestinal tract disorders (OR: 0.57, 95% CI: 0.43–0.77, P= 0.12). Our meta-analyses suggest a protective effect of nonsteroidal anti-inflammatory drugs on the risk of adenocarcinoma. Our results also suggest that the drugs might act after the formation of Barrett's epithelium in the esophageal inflammation – Barrett's esophagus – adenocarcinoma sequence.