Obesity, H pylori and Risk of Barrett's Esophagus

肥胖、幽门螺杆菌和巴雷特食管的风险

• 批准号: 7210092
• 负责人: Hashem B El-Serag
• 金额: $ 56.94万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7210092
• 关键词: Acidity; Acids; Affect; Age; Agonist; Alcohol consumption; Antacids; Atrophic Gastritis; Barrett Esophagus; Bile Acids; Bile fluid; Biliary; Body fat; Body mass index; Body of uterus; Calcium Channel Blockers; Caring; Case-Control Studies; Central obesity; Clinical; Colonoscopy; Cross-Sectional Studies; Dietary intake; Endoscopy; Epithelium; Esophageal; Esophageal Adenocarcinoma; Esophagus; Exposure to; Fatty acid glycerol esters; Gastric Acid; Gastric Parietal Cells; Gastritis; Gastroesophageal reflux disease; Gender; Helicobacter Infections; Helicobacter pylori; Hernia; Histamine H2 Receptors; Human Papillomavirus; Infection; Inflammatory; Intra-abdominal; Lesion; Life Style; Malignant Neoplasms; Measures; Mediator of activation protein; Modeling; Nested Case-Control Study; Newly Diagnosed; Obesity; PTGS2 gene; Patients; Peptic Esophagitis; Persons; Pharmaceutical Preparations; Physical activity; Premalignant; Prevalence; Proton Pump Inhibitors; Pylorus; Race; Reflux; Research Personnel; Risk; Risk Factors; Screening procedure; Serum; Severities; Smoking; Sphincter; Stomach; Symptoms; TNF gene; TP53 gene; Tissues; Visceral; X-Ray Computed Tomography; abdominal fat; abdominal pressure; adiponectin; design; interest; men; pressure; programs; protective effect; tumor progression

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).

描述（由申请人提供）：Barrett的食管（BE）是唯一已知的食管腺癌的癌前病变，这是美国白人中最快的恶性肿瘤。 BA的危险因素在很大程度上未知。我们计划研究嵌套在大型横断面研究中的病例对照研究中的潜在危险因素，其主要目的是估算肥胖与BE之间的关联，以及估计螺旋杆菌（H. Pylori）感染与BE之间的关联的次要目的。肥胖症已被确定为食管腺癌的危险因素。然而，肥胖是否增加了BE的风险仍然未知。我们假设肥胖症，尤其是大量内脏腹部脂肪是BE的危险因素。我们计划估计体内脂肪的数量和分布对BE患病率的影响。我们将比较有或没有BE的患者（体重指数（BMI），腹部肥胖症，特别是通过CT-SCAN；以及与内脏肥胖相关的炎症介体测量的腹腔内（内脏）脂肪的量的以下变量（11-6，TNF，脂肪素）。这种保护作用的机制是通过形成萎缩性胃炎，导致胃酸分泌的降低，我们计划检查幽门螺杆菌感染的流行，感染的类型（CAGA产生菌株），并在没有效果的情况下进行胃炎（胃炎）的分布和严重性。饮食摄入，吸烟，药物和体育锻炼）；我们将研究感兴趣的暴露（肥胖和幽门螺杆菌）对酸和胆汁相关损伤严重程度（COX-2）以及BE中的肿瘤进展的组织标记的影响（例如，体p53和p16灭活）。我们计划针对上内窥镜的连续合格患者进行横断面研究，以进行非紧急适应症。此外，我们对随机选择的人进行了一项横断面研究，有资格在休斯顿VAMC接受护理（并有资格接受筛查结肠镜检查）。随后，在一项病例对照研究中，将检查所有新诊断的BE和随机选择的对照组的内脏肥胖体积和活性（CT扫描和血清脂肪细胞因子）。