Racial Disparity in Barrett's Esophagus

摘要： Barrett食管（BE）是一种易诱发人食管腺癌（EAC）的癌前病变，已知主要累及美国白人。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上皮化生的过程，并且肠转录因子（例如，Cdxl和Cdx 2）对该过程至关重要。Cdx 1和Cdx 2都是通过启动子甲基化的缺失在食管上皮细胞中诱导和表达的。Cdx 2基因在人体内的转染 食管鳞状上皮细胞诱导形态学和基因表达的化生变化。在这个建议中，我们假设环境因素，遗传因素，和潜在的基因-环境相互作用在所观察到的种族差异在BE中起着至关重要的作用。临床数据，胃分泌物，内镜检查 将从白种人和非裔美国人患者中采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。我们推测，遗传危险因素的差异分布使美国白人比非洲裔美国人更容易患BE。了解 病变的发病机制是至关重要的，未来的尝试，以防止化生和发育异常的变化，在食管。

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.