Genetic Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma

项目总结 食管腺癌(EAC)的发病率在过去的30年里增加了5倍以上 而预后仍然很差。巴雷特食道(BE)是唯一已知的EAC前体。 内窥镜检查(EGD)是诊断BE的唯一方法，但由于EGD费用昂贵，筛查费用不高 建议在诊断前的BE患者中检测到极少的EAC。对世界产生影响 预防和早期发现EAC挑战是首先开发一种替代方法进行筛查 在可接受和可获得的同时，比EGD成本更低、更安全。一种非内窥镜检测方法 将允许在初级保健环境中进行筛查。波形蛋白和其他标志物的异常甲基化可能是 在90%以上的BE受试者中，从内窥镜刷牙提取的DNA中检测到。BETRNet补充资料 该项目旨在将我们发现的BE和EAC的表观遗传标记直接翻译到临床上 BE检测和风险分层的新方法。这个项目是从甲基化的发现发展而来的 基因，有可能作为BE或EAC的检测生物标志物。本项目： 1)使用一种新的非内窥镜食道远端采样方法来确定 甲基化标记作为BE的检测标记； 2)确定一组异常甲基化的基因是否与高度不典型增生和 可以在食道刷检或非内窥镜下的食道远端样本中检测到EAC，以使 风险分层战略； 该补充项目显然旨在对降低以下疾病的死亡率产生重大的翻译影响 EAC通过开发一种方便的非侵入性筛查方案。

PROJECT SUMMARY The incidence of esophageal adenocarcinoma (EAC) has increased more than 5-fold in the past three decades while the prognosis has remained poor. Barrett's esophagus (BE) is the only known precursor of EAC. Endoscopy (EGD) is the only method to diagnose BE but because EGD is expensive and screening is not recommended very few EACs are detected in patients with pre-diagnosed BE. To make an impact on the prevention and early detection of EAC the challenge is to first develop an alternative method for screening that is less costly and safer than EGD while being acceptable and accessible. A non-endoscopic detection method would allow screening in the primary care setting. Aberrant methylation of vimentin and other markers can be detected in DNA extracted from endoscopic brushings in over 90% of BE subjects. The BETRNet supplemental project aims to directly translate these epigenetic markers of BE and EAC that we have discovered to clinically novel methods for detection and risk stratification of BE. This project grows out of the discovery that methylated genes, have the potential to be used as detection biomarkers for BE or EAC. This project: 1) Uses a novel non-endoscopic distal esophageal sampling method to determine the accuracy of methylation markers as detection markers for BE; 2) Determines whether a panel of aberrantly methylated genes associated with high grade dysplasia and EAC can be detected in esophageal brushings or nonendoscopic distal esophageal samples to enable risk stratification strategies; The supplemental project is clearly aimed at having significant translational impact at decreasing mortality from EAC through the development of a convenient non-invasive screening program.