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: 8132798
• 负责人: JOEL H RUBENSTEIN
• 金额: $ 13.62万
• 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/8132798
• 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; Interleukin-6; 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 effective; 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）：

项目成果

Helicobacter pylori DNA decreases pro-inflammatory cytokine production by dendritic cells and attenuates dextran sodium sulphate-induced colitis.

• DOI: 10.1136/gut.2010.220087
• 发表时间: 2011-11
• 期刊: Gut
• 影响因子: 24.5
• 作者: Luther J;Owyang SY;Takeuchi T;Cole TS;Zhang M;Liu M;Erb-Downward J;Rubenstein JH;Chen CC;Pierzchala AV;Paul JA;Kao JY
• 通讯作者: Kao JY

Shedding some light on the etiology of adenocarcinomas of the esophagus and gastric cardia.

揭示食管和贲门腺癌的病因学。

• DOI: 10.1038/ajg.2012.337
• 发表时间: 2012
• 期刊: The American journal of gastroenterology
• 作者: Rubenstein,JoelH

Prevalence and risk factors for heterotopic gastric mucosa of the upper esophagus among men undergoing routine screening colonoscopy.

接受常规结肠镜筛查的男性上食管异位胃粘膜的患病率和危险因素。

• DOI: 10.1111/dote.12221
• 发表时间: 2015
• 期刊: Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus
• 作者: Govani,SM;Metko,V;Rubenstein,JH
• 通讯作者: Rubenstein,JH

Barrett's esophagus progressing to cancer: a needle in a haystack?

巴雷特食管进展为癌症：大海捞针？

• DOI: 10.1016/j.cgh.2010.11.037
• 发表时间: 2011
• 期刊: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
• 作者: Lewis,JasonJ;Rubenstein,JoelH
• 通讯作者: Rubenstein,JoelH

The impact of rotating shift work on the prevalence of irritable bowel syndrome in nurses.

• DOI: 10.1038/ajg.2010.48
• 发表时间: 2010-04
• 期刊: AMERICAN JOURNAL OF GASTROENTEROLOGY
• 影响因子: 9.8
• 作者: Nojkov, Borko;Rubenstein, Joel H.;Chey, William D.;Hoogerwerf, Willemijntje A.
• 通讯作者: Hoogerwerf, Willemijntje A.