The Epidemiology of Adipokines in Barrett's Esophagus

巴雷特食管中脂肪因子的流行病学

• 批准号: 7492658
• 负责人: JOEL H RUBENSTEIN
• 金额: $ 16万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-10 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7492658
• 关键词: Address; Adipocytes; Advisory Committees; Apoptosis; Barrett Esophagus; Bioinformatics; Biological Markers; Blood; Blood Circulation; Body mass index; Case-Control Studies; Condition; Development; Dysplasia; Endoscopy; Epidemiology; Epithelial; Esophageal; Esophageal Adenocarcinoma; Esophagus; Fatty acid glycerol esters; Future; Gastric Cardia Adenocarcinoma; Gastroesophageal reflux disease; Goals; Health; Incidence; Inflammation; Inflammatory; Intestines; Malignant Neoplasms; Measurement; Mechanics; Mediating; Medical; Mentors; Metaplasia; Molecular Weight; Mucous Membrane; National Cancer Institute; Numbers; Obesity; Patients; Plasma; Protein Isoforms; Purpose; Reflux; Research; Research Personnel; Risk; Risk Factors; Screening procedure; Serum; Signal Pathway; Somatomedins; Symptoms; Testing; Tissues; Translational Research; United States; United States National Institutes of Health; Visceral; adipokines; adiponectin; adipsin; cancer type; career; case control; cohort; cost; cytokine; experience; ghrelin; leptin receptor; model development; mortality; novel; novel strategies; obesity risk; prevent; programs; prospective; resistin; stomach cardia; translational study

DESCRIPTION (provided by applicant): The incidence of esophageal adenocarcinoma (EAC) is rising faster than that of any other cancer, and the 5- year mortality of this cancer type is 86%. The long-term career objective of the candidate is to develop novel cost-effective strategies for preventing mortality from EAC. Any such strategy will depend on identifying patients at risk for EAC. Barrett's esophagus (BE) is the accepted precursor of EAC. The immediate career objective is to develop novel strategies of identifying patients at risk for BE for the purpose of screening. Obesity is a risk factor for BE and EAC. Others have proposed that this effect is mediated by a mechanical effect promoting gastroesophageal reflux disease. We believe it is unlikely that the risk is due solely to such a mechanical effect; instead, we propose that visceral adipocytes secrete cytokines (adipokines) that promote BE and EAC. Adiponectin, an adipokine whose serum levels are inversely correlated with obesity, inhibits inflammation and promotes apoptosis; deficiency is associated with a number of epithelial cancers. The high molecular weight (HMW) form of adiponectin may be the metabolically active form. We hypothesize that adiponectin deficiency (and the HMW isoform in particular) is closely associated with BE, and is associated with progression of BE toward EAC. We propose a prospective case-control study to estimate the relation between adiponectin in plasma and BE, controlling for potential confounding factors. In addition to examining a potential mechanism to explain the effect of obesity on BE, we hope to identify in adiponectin deficiency a new biomarker of high risk for development of BE. The proposed translational study addresses priorities identified by the National Cancer institute, including to identify "pathophysiologic consequences of reflux, and its interrelationship with BMI, fat distribution, and other factors in the development of esophageal and gastric cardia adenocarcinomas and their precursors." The candidate's career will be developed through the mentored research experience and through didactic courses in epidemiology and bioinformatics. RELEVANCE: The incidence of esophageal adenocarcinoma is rising faster than that of any other cancer in the U.S. This highly fatal cancer is associated with obesity. This study tests the hypothesis that specific substances secreted from fat tissue are strongly associated with the risk of developing esophageal adenocarcinoma. If so, measurement of these substances may be useful in a screening program.

描述（由申请人提供）： 食管腺癌（EAC）的发病率比任何其他癌症都快上升，这种癌症类型的5年死亡率为86％。候选人的长期职业目标是制定新颖的成本效益策略来防止EAC死亡。任何此类策略都将取决于确定有EAC风险的患者。巴雷特的食道（BE）是EAC的公认前体。直接的职业目标是制定新的策略来确定出于筛查目的的风险。肥胖是BE和EAC的危险因素。其他人则提出，这种作用是由促进胃食管反流疾病的机械作用介导的。我们认为，风险不太可能仅由于这种机械效应。取而代之的是，我们建议内脏脂肪细胞分泌促进BE和EAC的细胞因子（脂肪因子）。脂联素是一种脂肪因子，其血清水平与肥胖成反比，抑制炎症并促进凋亡。缺陷与许多上皮癌有关。脂联素的高分子量（HMW）形式可能是代谢活性形式。我们假设脂联素缺乏症（尤其是HMW同工型）与BE密切相关，并且与BE向EAC的进展相关。我们提出了一项前瞻性病例对照研究，以估计血浆和BE中脂联素之间的关系，从而控制潜在的混杂因素。除了检查一种潜在的机制来解释肥胖对BE的影响外，我们还希望在脂联素缺乏症中识别出一种新的BE发育风险的新生物标志物。拟议的翻译研究旨在解决国家癌症研究所确定的优先级，包括确定“反流的病理生理后果，及其与BMI，脂肪分布，脂肪分布和其他因素的相互关系，以及食管和胃病腺癌的发展中的其他因素。”候选人的职业将通过指导的研究经验以及流行病学和生物信息学的教学课程发展。相关性：食管腺癌的发病率上升的速度比美国其他任何其他癌症都快，这种高度致命的癌症与肥胖有关。这项研究检验了以下假设：脂肪组织分泌的特定物质与患食道腺癌的风险密切相关。如果是这样，对这些物质的测量可能在筛选程序中很有用。