Changes Associated With H. Pylori and Gastric Carcinogenesis

Study Overview
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Brief Summary
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This is a research study for patients who currently have or previously had an H. pylori infection or who have gastric or esophageal cancer and who plan to undergo an endoscopy as part of their care. The purpose of this study is to find out how and why H. pylori infections can cause progression to gastric cancer and if it's possible for intervention prior to this progression.

Detailed Description
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H. pylori infection is a prevalent environmental cause of gastric cancer. The molecular mechanisms of carcinogenesis due to H. pylori remain unexplained and consequences of infection are variable and unpredictable. The aim of this research is to examine the RNA transcriptome of gastric cancer mucosa (gastric mucosa is the mucus membrane of the stomach), in patients with H. pylori infection and examine the spectrum of disease associated with infection. We will also examine bacterial content of samples to pinpoint the specific H. pylori strain(s) and the stomach microbial profile to correlate with the gastric mucosal transcriptome and predisposition of gastric cancer. Patients with prior or current active H. pylori infection who are planning to under endoscopic evaluation will be eligible for participation. From these patients, we plan to take up to four additional biopsies from each area of stomach already being sampled. The biopsies will be used for next-generation RNA and DNA sequencing and novel bioinformatics analyses. The analysis will be performed at Weill Cornell Medical College by Doron Betel, PhD. The sequencing will be performed in the Epigenetics Core laboratory under the supervision of Doron Betel, who will be working closely with the principal investigator, Manish A. Shah, M.D. Examination of the genetic impact of H. pylori infection in patients may expose genetic factors that influence gastric cancer carcinogenesis and give deeper insight into molecular pathways that serve as candidate biomarkers for gastric cancer carcinogenesis. Our goal is to distinguish patients with chronic H. pylori infection who are at risk of subsequently developing gastric cancer from the vast majority of patients with H. pylori infection who do not develop malignancy.

Official Title
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Next-Generation Sequencing to Evaluate Transcriptomic Changes Associated With H. Pylori Infection and Gastric Cancer Carcinogenesis

Conditions
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Bacterial Infection Due to Helicobacter Pylori (H. Pylori)

Intervention / Treatment
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* Procedure: Endoscopy tissue collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must be 18 years or older Patient must have active or prior H. pylori infection, or have been treated for H.pylori infection in the past, as assessed by ELISA (not applicable for the subset of patient controls) or have gastric or esophageal cancer or have Barrett's Esophagus Patients must be eligible for and are planning to undergo a routine upper endoscopy and tissue biopsy Patients must sign informed consent Exclusion Criteria: Prior history of upper GI bleed (within 3 months) Bleeding disorder or coagulopathy Recent stroke or myocardial infarction (within 3 months)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patient<br>Subjects for this study will be either H. pylori positive with an active infection, cleared of an H. pylori infection or be both H. pylori antibody positive and have a malignancy of the gastrointestinal tract, specifically gastric adenocarcinoma. | Procedure: Endoscopy tissue collection<br>* The investigational part of this study is the requirement for an additional biopsy from a site that is already being biopsied at the time of a routine endoscopy. Any patients who develop bleeding following their routine clinical biopsies will not undergo any additional research biopsies.<br>|
| Control<br>A small subset of patients without H. pylori infection will be enrolled as well (n=30) to serve as a control group. | Procedure: Endoscopy tissue collection<br>* The investigational part of this study is the requirement for an additional biopsy from a site that is already being biopsied at the time of a routine endoscopy. Any patients who develop bleeding following their routine clinical biopsies will not undergo any additional research biopsies.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in tranional profiles of samples | Identify differences in tranional profiles and dysregulated pathways between patient groups with variable response to H. pylori infection | at time of sample collection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Examine bacterial content in samples | High-throughput DNA and RNA sequencing will be used to determine bacterial content of samples | at time of sample collection |