Racial Disparity in Barrett's Esophagus

巴雷特食管的种族差异

基本信息

批准号：
8068502
负责人：
NICHOLAS J SHAHEEN
金额：
$ 42.43万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-28 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8068502
关键词：
Acids Adenocarcinoma African American Appearance Applications Grants Area Aspirate substance Barrett Esophagus Bile Acids Biopsy Biopsy Specimen Blood specimen Carcinogen exposure Carcinoma Caucasians Caucasoid Race Characteristics Clinical Data Color Data Deglutition Diagnosis Disease Distal Dysplasia Employee Strikes Endoscopic Biopsy Endoscopy Environmental Exposure Environmental Risk Factor Epigenetic Process Epithelial Cells Esophageal Esophageal Adenocarcinoma Esophageal Diseases Esophagus Exposure to Future Gastroesophageal reflux disease Gene Expression Genes Genetic Health Status Helicobacter pylori Hiatal Hernia Histologic Human Intestinal Metaplasia Intestines Lesion Malignant neoplasm of esophagus Measurement Mediating Metaplasia Metaplastic Methylation Monitor Morphology Pathogenesis Pathway interactions Patients Pepsin A Play Process Promoter Regions Questionnaires Recruitment Activity Reflux Reporting Role Salmon Series Single Nucleotide Polymorphism Smoking Squamous Epithelium Squamous Hyperplasia Squamous cell carcinoma Staining method Stains Techniques Testing Tissues Transfection Trypsin abstracting caucasian American demographics drinking electric impedance gastric secretion substance gene environment interaction genetic risk factor patient population prevent promoter transcription factor

项目摘要

Abstract: Barrett's esophagus (BE), a prelimalignant disease predisposing to human esophageal adenocarcinoma (EAC), is known to predominantly afflict Caucasian Americans. Our preliminary data have shown that in human BE a series of genes and pathways are activated to mediate the process of intestinal metaplasia, and thatintestinal transcription factors (e.g., Cdxl and Cdx2) are crucial to this process. Both Cdx1 and Cdx2 are induced and expressed in esophageal epithelial cells through loss of promoter methylation. Transfection of Cdx2 into human esophageal squamous epithelial cells induces metaplastic changes in morphology and gene expression. In this proposal, we hypothesize that environmental factors, genetic factors, and potentially gene-environment interactions play crucial roles in the observed racial disparity in BE. Clinical data, gastric secretions, endoscopic biopsy samples and blood samples will be collected from Caucasian and African American patients to identify critical environmental and genetic factors leading to BE. We hypothesize that differential distribution of genetic risk factors make Caucasian Americans more susceptible to BE than African Americans. Understanding the pathogenesis of the lesion is vital to future attempts at preventing metaplastic and dysplastic changes in the esophagus.

抽象的： Barrett的食道（BE）是一种易受人类食管腺癌（EAC）的初步疾病，众所周知，主要是苦苦挣扎的白种人。我们的初步数据表明，在人类中，一系列基因和途径被激活以介导肠道化生的过程，而刻内转录因子（例如，CDXL和CDX2）对这一过程至关重要。 CDX1和CDX2均通过启动子甲基化丧失在食管上皮细胞中诱导和表达。将CDX2转染到人食管鳞状上皮细胞诱导形态和基因表达的化生变化。在此提案中，我们假设环境因素，遗传因素和潜在的基因环境相互作用在观察到的种族差异中起着至关重要的作用。临床数据，胃分泌物，内窥镜检查将从高加索和非裔美国人患者那里收集活检样本和血液样本，以鉴定导致的关键环境和遗传因素。我们假设遗传危险因素的差异分布使高加索美国人比非裔美国人更容易受到影响。了解病变的发病机理对于预防食道的转移和异型变化的未来尝试至关重要。