Role of H. Pylori Infection in Esophageal Adenocarcinoma

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DESCRIPTION (provided by applicant): The prevalence of Helicobacter pylori colonisation in populations in developed country has been declining. The decreasing prevalence of cagA+ Helicobacter pylori may be associated with the rising incidence of esophageal adenocarinomas in industrialized countries. Colonization with cagA+ strains has been shown to be inversely associated with reflux esophagitis and Barrett's esophagus. A lower prevalence of cagA+ Helicobacter pylori has been observed in patient with gastroesophageal reflux disease (GERD) which results from acid exposure to the esophagus. One explanation for the negative association between colonization with Helicobacter pylori and GERD is the effect of Helicobacter pylori on acid production. Eradication of Helicobacter pylori has led to the development of GERD in a proportion of treated patients. These clinical evidence has led to the hypothesis that Helicobacter pylori could play a protective role in the development of GERD, especially reflux esophagitis. Experiments proposed in the following specific aims will test the hypothesis that Helicobacter pylori, especially the cagA+ strains, may protect against GERD, Barrett's esophagus and esophageal adenocarcinoma. The specific aims are as follows: 1. To study the effects of gastric colonization of cagA+ and cagA- strains of Helicobacter pylori on host inflammatory responses in rats and mice. 2. To determine the effects of Helicobacter pylori infection in reflux esophagitis, Barrett's esophagus and esophageal adenocarcinoma in a surgical reflux model in rats. 3. To determine the effects of Helicobacter pylori infection in esophagitis, Barrett's esophagus and esophageal adenocarcinoma in a surgical reflux model in wild-type and p53 knockout mice. The proposed studies aim to ascertain the role of Helicobacter pylori colonization in the development of reflux esophagitis, Barrett's esophagus and its associated adenocarcinoma in rodent models. This proposal utilizes the innovative surgical models of GERD, BE and EAC for studying the protective role of Helicobacter pylori against reflux complications.