Racial Disparity in Barrett's Esophagus

巴雷特食管的种族差异

• 批准号: 8068482
• 负责人: XIAOXIN Luke CHEN
• 金额: $ 35.81万
• 依托单位: NORTH CAROLINA CENTRAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8068482
• 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; Stomach; Techniques; Testing; Tissues; Transfection; Trypsin; caucasian American; demographics; drinking; electric impedance; gastric secretion substance; gene environment interaction; genetic risk factor; patient population; prevent; promoter; transcription factor

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 Cdxl and Cdx2 are induced and expressed in esophageal epithelial cells through loss ef 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.

巴雷特食管（BE）是一种易致人类食管腺癌（EAC）的癌前病变，已知主要发生在美国白种人身上。我们的初步数据表明，在人BE中，一系列基因和途径被激活来介导肠化生过程，肠道转录因子（如Cdxl和Cdx2）在这一过程中起着至关重要的作用。Cdxl和Cdx2都是通过丢失启动子甲基化在食管上皮细胞中诱导和表达的。将Cdx2转染人食管鳞状上皮细胞可引起形态学和基因表达的化生变化，在本研究中，我们假设环境因素、遗传因素以及潜在的基因-环境相互作用在BE中观察到的种族差异中起关键作用。临床资料，胃分泌物，内窥镜