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: 8036057
• 负责人: Hashem B El-Serag
• 金额: $ 50.5万
• 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 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8036057
• 关键词: Acidity; Acids; Affect; Age; Agonist; Alcohol consumption; Antacids; Atrophic; Atrophic Gastritis; Bacteria; Barrett Esophagus; Bile Acids; Bile fluid; Body fat; Body mass index; Calcium Channel Blockers; Caring; Case-Control Studies; Central obesity; Chronic; Clinical; Colonoscopy; Cross-Sectional Studies; Dietary intake; Disease; Endoscopy; Esophageal; Esophageal Adenocarcinoma; Esophageal Tissue; Exposure to; Fatty acid glycerol esters; Gastric Acid; Gastritis; Gastroesophageal reflux disease; Gender; Helicobacter Infections; Helicobacter pylori; Hernia; Histamine H2 Receptors; Human Papillomavirus; Individual; Infection; Inflammation; Inflammation Mediators; Institution; Interleukin-6; Intra-abdominal; Intrinsic factor; Lesion; Life Style; Low Prevalence; Malignant Neoplasms; Measures; Nested Case-Control Study; Newly Diagnosed; Obesity; PTGS2 gene; Pathogenesis; Patients; Persons; Pharmaceutical Preparations; Physical activity; Predictive Factor; Premalignant; Prevalence; Prevention; Production; Proton Pump Inhibitors; Race; Risk; Risk Factors; Screening procedure; Serum; Severities; Smoking; Stomach; Symptoms; TNF gene; Tissues; United States; Visceral; X-Ray Computed Tomography; abdominal fat; adiponectin; design; illness length; interest; men; modifiable risk; 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（由申请方提供）：巴雷特食管（BE）是唯一已知的食管腺癌癌前病变，是美国白色男性中增长最快的恶性肿瘤。BE的风险因素在很大程度上是未知的。我们计划在一项大型横断面研究中进行一项病例对照研究，研究BE的潜在危险因素，主要目的是评估肥胖与BE之间的相关性，次要目的是评估幽门螺杆菌（H. pylori感染和BE。肥胖已被确定为食管腺癌的危险因素。然而，肥胖是否会增加BE的风险仍不清楚。我们推测肥胖，特别是大量的内脏腹部脂肪是BE的危险因素。我们计划评估体脂的数量和分布对BE患病率的影响。我们将比较BE患者和非BE患者之间的以下变量（体重指数（BMI）、腹部肥胖，特别是通过CT扫描测量的腹腔内（内脏）脂肪量;以及与内脏肥胖相关的炎症介质（11-6、TNF、脂联素）。我们假设H. pylori感染，特别是CagA阳性菌株，对BE具有保护作用，这种保护作用的机制是通过形成萎缩性胃炎，从而减少胃酸分泌。我们计划检查H.幽门螺杆菌感染，感染类型（CagA产生菌株），以及BE病例和非BE病例中胃炎（胃体炎）的分布和严重程度。我们将检查主要暴露的影响，同时调整生活方式特征（例如饮食摄入、吸烟、药物和体力活动）;人口统计学特征（年龄、性别、种族）;和临床特征（例如食管裂孔疝、GERD症状的持续时间和严重程度）。我们将研究我们感兴趣的暴露（肥胖和H。pylori）对指示酸和胆汁相关损伤（考克斯-2）的严重性以及BE中的肿瘤进展（例如体细胞p53和p16失活）的BE组织标记物的影响。我们计划对因非紧急适应症接受上消化道内镜检查的连续合格患者进行横断面研究。此外，我们在随机选择的有资格在休斯顿VAMC接受治疗（并有资格接受筛查结肠镜检查）的人中进行了一项横断面研究。随后，在病例对照研究中，将检查所有新诊断的BE和随机选择的对照的内脏肥胖的体积和活动（CT扫描和血清脂肪细胞因子）。

项目成果

Sequential and concomitant therapy with four drugs is equally effective for eradication of H pylori infection.

• DOI: 10.1016/j.cgh.2009.09.030
• 发表时间: 2010-01
• 期刊: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
• 作者: Wu DC;Hsu PI;Wu JY;Opekun AR;Kuo CH;Wu IC;Wang SS;Chen A;Hung WC;Graham DY
• 通讯作者: Graham DY

The association between Barrett's esophagus and Helicobacter pylori infection: a meta-analysis.

• DOI: 10.1111/j.1523-5378.2011.00931.x
• 发表时间: 2012-06
• 期刊: Helicobacter
• 影响因子: 4.4
• 作者: Fischbach LA;Nordenstedt H;Kramer JR;Gandhi S;Dick-Onuoha S;Lewis A;El-Serag HB
• 通讯作者: El-Serag HB

The association between obesity and GERD: a review of the epidemiological evidence.

• DOI: 10.1007/s10620-008-0413-9
• 发表时间: 2008-09
• 期刊: DIGESTIVE DISEASES AND SCIENCES
• 影响因子: 3.1
• 作者: El-Serag, Hashem

Medication usage and the risk of neoplasia in patients with Barrett's esophagus.

• DOI: 10.1016/j.cgh.2009.06.001
• 发表时间: 2009-12
• 期刊: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
• 作者: Nguyen DM;El-Serag HB;Henderson L;Stein D;Bhattacharyya A;Sampliner RE
• 通讯作者: Sampliner RE

Obscure gastrointestinal bleeding: where do we go from here?

隐匿性胃肠道出血：我们该何去何从？

• DOI: 10.1053/j.gastro.2010.03.023
• 发表时间: 2010
• 期刊: Gastroenterology
• 影响因子: 29.4
• 作者: Leung,WaiK;Graham,DavidY
• 通讯作者: Graham,DavidY