Racial Disparity in Barrett's Esophagus

摘要： 巴雷特食道(BE)是一种易患人类食管腺癌(EAC)的初步恶性疾病，已知主要困扰高加索美国人。我们的初步数据表明，在人类BE中，一系列基因和途径被激活以介导肠化生过程，而肠道转录因子(如CDX1和CDX2)在这一过程中起着至关重要的作用。CDX1和CDX2都是通过缺失启动子甲基化在食道上皮细胞中诱导和表达的。CDX2基因导入人体内的研究 食道鳞状上皮细胞诱导形态和基因表达的化生改变。在这一建议中，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着关键作用。临床资料、胃液、内窥镜检查 将从高加索人和非裔美国人患者身上收集活检样本和血液样本，以确定导致BE的关键环境和遗传因素。我们假设，遗传风险因素的不同分布使高加索美国人比非裔美国人更容易患上这种疾病。了解 病变的发病机制对于未来预防食管化生和异型增生的尝试至关重要。

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.