The Epidemiology of Adipokines in Barrett's Esophagus

描述（由申请人提供）： 食管腺癌（EAC）的发病率上升速度比任何其他癌症都快，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开发新的具有成本效益的策略，以预防EAC死亡。任何这样的策略都将取决于识别有EAC风险的患者。Barrett食管（BE）是公认的EAC的前体。近期的职业目标是开发新的策略，以识别处于BE风险中的患者，以进行筛查。肥胖是BE和EAC的危险因素。其他人提出，这种作用是由促进胃食管反流病的机械作用介导的。我们认为这种风险不太可能仅仅是由于这样的机械效应;相反，我们提出内脏脂肪细胞分泌细胞因子（脂肪因子），促进BE和EAC。脂联素是一种脂肪因子，其血清水平与肥胖呈负相关，可抑制炎症并促进细胞凋亡;脂联素缺乏与许多上皮癌相关。脂联素的高分子量（HMW）形式可以是代谢活性形式。我们推测脂联素缺乏（特别是高分子量异构体）与BE密切相关，并与BE向EAC的进展有关。我们提出了一个前瞻性病例对照研究，以估计血浆脂联素和BE之间的关系，控制潜在的混杂因素。除了研究解释肥胖对BE影响的潜在机制外，我们还希望在脂联素缺乏症中鉴定出一种新的BE高风险生物标志物。拟议的转化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BMI，脂肪分布和食管和贲门腺癌及其前体发展中的其他因素的相互关系。“候选人的职业生涯将通过指导的研究经验和通过流行病学和生物信息学的教学课程来发展。相关性：在美国，食管腺癌的发病率比任何其他癌症的发病率都要快。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食管腺癌发生风险密切相关的假设。如果是这样，这些物质的测量可能是有用的筛选程序。

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.