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: 7677289
• 负责人: JOEL H RUBENSTEIN
• 金额: $ 15.85万
• 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/7677289
• 关键词: Address; Adipocytes; Advisory Committees; Apoptosis; Barrett Esophagus; Bioinformatics; Biological Markers; Blood; Blood Circulation; Body mass index; Case-Control Studies; Development; Dysplasia; Endoscopy; Epidemiology; Epithelial; Esophageal; Esophageal Adenocarcinoma; Esophagus; Fatty acid glycerol esters; Future; Gastric Cardia Adenocarcinoma; Gastroesophageal reflux disease; Goals; Health; Incidence; Inflammation; Intestines; Malignant Neoplasms; Measurement; Mechanics; Mediating; Medical; Mentors; Metaplasia; Molecular Weight; Mucous Membrane; National Cancer Institute; Obesity; Patients; Plasma; Protein Isoforms; 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; high risk; inflammatory marker; 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)的发病率上升速度比其他任何癌症都要快，5年死亡率为86%。候选人的长期职业目标是开发新的具有成本效益的战略，以防止EAC死亡。任何此类策略都将取决于识别易患EAC的患者。巴雷特食道(BE)是公认的EAC的前体。目前的职业目标是开发新的策略来识别BE的风险患者，以便进行筛查。肥胖是BE和EAC的风险因素。其他人提出，这种效应是由促进胃食道反流病的机械效应介导的。我们认为，这种风险不太可能完全源于这种机械效应；相反，我们认为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，其血清水平与肥胖呈负相关，它抑制炎症并促进细胞凋亡；脂联素缺乏与许多上皮性癌症有关。脂联素的高相对分子质量(HMW)形式可能是代谢活性形式。我们推测，脂联素缺乏(尤其是HMW亚型)与BE密切相关，并与BE向EAC的进展有关。我们提出了一项前瞻性病例对照研究，以估计血浆脂联素与BE的关系，控制潜在的混杂因素。除了研究肥胖对BE影响的潜在机制外，我们还希望在脂联素缺乏症中发现一种新的BE高危生物标志物。这项拟议的翻译研究解决了国家癌症研究所确定的优先事项，包括确定“反流的病理生理后果，及其与体重指数、脂肪分布的相互关系，以及在食道腺癌和贲门腺癌及其前驱病变的发展过程中的其他因素。”候选人的职业生涯将通过指导研究经验和流行病学和生物信息学的教学课程来发展。相关性：食管腺癌的发病率比美国其他任何癌症的上升速度都要快。这种高度致命的癌症与肥胖有关。这项研究验证了脂肪组织分泌的特定物质与患食管腺癌风险密切相关的假设。如果是这样的话，这些物质的测量在筛查计划中可能是有用的。