ROLE OF BACTERIAL COLONIZATION IN DEVELOPMENT OF UPPER GI PATHOLOGY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The investigators hypothesize the following: 1) Normal bacterial flora exists in the esophagus and that they change during the evolution of gastroesophageal reflux disease (GERD) into Barrett's esophagus and esophageal adenocarcinoma. 2) Specific host and bacterial factors may determine the development of esophageal disease. 3) The IL-1b-31*T allele and the functionally related IL-1RN*2 allele decrease the risk of esophageal inflammation, metaplasia, and consequent development of adenocarcinoma by modulating the host inflammatory response to H. pylori and subsequent acid production and cellular proliferation. The specific aims are as follows: 1. To define the bacterial flora at a population level in the normal esophagus and the esophagus of patients with GERD-related diseases such as esophagitis and Barrett's esophagus 2. To define the bacterial flora at a species level in the normal esophagus and the esophagus of patients with GERD-related diseases. 3. To determine host humoral immune responses to the esophageal colonizing bacteria in patients with a normal esophagus or with GERD-related diseases. 4. To assess the presence of H. pylori and its strain characteristics in patients with and without reflux disease 5. To assess for the progression of atrophic gastritis by examination of serum pepsinogens in the patients with GERD or with normal esophagus 6. To determine the effect of Helicobacter pylori strain characteristics on gastric and esophageal mucosal IL-1b protein expression, and on the development of inflammation, metaplasia, and dysplasia. 7. To determine the prevalence of the IL-1b-31 and IL-1RN alleles in relation to esophageal acid exposure, also in relation to H. pylori colonization. In particular, we also will evaluate the effect of the IL-1b-31 and IL-1RN alleles on gastroesophageal junction (GEJ) cellular proliferation and cyclooxygenase-2 (COX-2) expression in patients with or without H. pylori colonization. 8. To evaluate the effect of H. pylori eradication on GEJ cellular proliferation, and on IL-1b and COX-2 expression in relation to the IL-1b-31 allele The study will be conducted in outpatients referred for endoscopic evaluation for clinically indicated reasons. Endoscopic evaluation will be performed to assess for gastrointestinal pathology, esophageal bacterial colonization, and H. pylori colonization. Biopsies will be subjected to histologic review as well as determination of COX-2 expression as a marker of abnormal cellular regulation, and pH monitoring will be performed to determine esophageal acid exposure over 24 hours. Blood collected will be used for evaluating for serologic evidence of H. pylori colonization as well as for evaluating polymorphisms in the cytokine IL-1b gene locus. A total of 300 male and female patients between 18 and 75 years of age undergoing upper gastrointestinal endoscopy at Bellevue hospital and at the VANYHHS for clinically indicated reasons will be enrolled in this study. This study is an "add-on" study to an ongoing attempt to look at the role of bacterial colonization on the likelihood of GEJ inflammation (SPID #1229). It will utilize the same biopsy specimens as the original study but will also address the role of host genetics on the risk for inflammation. This study will help clarify the progression from reflux to Barrett's disease and to carcinoma.