Effect of Antireflux Therapy on the Expression of Genes in Patients With GERD

Although the symptomatic and epithelial (histologic and endoscopic) response to antireflux
therapy are well known and extensively studied, little is known of the genetic events
occurring in response to proton pump inhibitor therapy. Preliminary data from our laboratory
has shown, for example, that COX-2 expression is not only elevated in patients with
gastroesophageal reflux disease but also can be correlated with pathologic esophageal acid
exposure on 24 hour pH monitoring. Similar studies have suggested that antireflux surgery
may normalize COX-2 gene expression. In contrast studies following ablation of dysplastic
Barrett's epithelium have shown persistence of genetic changes associated with altered
cellular function, despite the return of the histologic appearance to normal. Several key
mediators of inflammation, metaplasia (Barrett's) and neoplasia have now been well
characterized and shown to be important factors in the pathogenesis of esophageal injury. It
is likely that successful antireflux therapy returns altered expression of these mediators
toward normal although this hypothesis remains largely unexplored. The aim of this study is
to investigate gene expression of key mediators of the spectrum of esophageal mucosal injury
and the response to antireflux therapy.

Hypothesis: Antireflux therapy (proton pump inhibitor and surgical fundoplication)
normalizes the expression of genes known to be involved in the pathogenesis of inflammation
(esophagitis), metaplasia (Barrett esophagus) and neoplasia (adenocarcinoma).