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Grant Details

Grant Number: 5R01CA116845-05 Interpret this number
Primary Investigator: El-Serag, Hashem
Organization: Baylor College Of Medicine
Project Title: Obesity, H Pylori and Risk of Barrett's Esophagus
Fiscal Year: 2011
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DESCRIPTION (provided by applicant): Barrett's esophagus (BE) is the only known precancerous lesion for esophageal adenocarcinoma, which is the fastest rising malignancy in white men in the US. Risk factors for BE are largely unknown. We plan to study potential risk factors for BE in a case-control study nested within a large cross-sectional study, with the primary aim of estimating the association between obesity and BE and a secondary aim of estimating the association between Helicobacterpylori (H. pylori) infection and BE. Obesity has been identified as a risk factor for esophageal adenocarcinoma. Yet, it remains unknown whether obesity increases the risk of BE. We hypothesize that obesity, especially a larger amount of visceral abdominal fat are risk factors for BE. We plan to estimate the effects of the amount and distribution of body fat on the prevalence of BE. We will compare the following variables between patients with and without BE (body mass index (BMI), abdominal obesity, specifically the amount of intra abdominal (visceral) fat measured by CT-scan; and inflammatory mediators associated with visceral obesity (11-6, TNF, adiponectin). We hypothesize that H. pylori infection, especially CagA positive strains, are protective against BE, and that the mechanism of this protective effect is through formation of corpus atrophic gastritis with consequent reduction in gastric acid secretion. We plan to examine the prevalence of H. pylori infection, type of infection (CagA producing strain), and distribution and severity of gastritis (corpus gastritis) in cases with BE and non- cases without BE. We will examine the effect of our main exposures while adjusting for lifestyle features (e.g. dietary intake, smoking, medications, and physical activity); demographic features (age, gender, race); and clinical features (e.g. hiatus hernia, duration and severity of GERD symptoms). We will examine the effect of our exposures of interest (obesity and H. pylori) on BE tissue markers indicative of severity of acid and bile-related damage (COX-2) as well as for neoplastic progression in BE (e.g. somatic p53 and p16 inactivation). We plan cross sectional study of consecutive eligible patients presenting to upper endoscopy for non-urgent indications. In addition, we conduct a cross-sectional study in randomly selected persons eligible to receive care (and eligible to receive screening colonoscopy) at the Houston VAMC. Subsequently, in a case-control study, all newly diagnosed BE and randomly selected controls will be examined for the volume and activity of visceral obesity (CT scan and serum adipocytokines).

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