Genetic Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma

项目摘要 食管腺癌（EAC）的发病率在过去三十年中增加了5倍以上 而预后仍然很差。Barrett食管（BE）是EAC唯一已知的前体。 内窥镜检查（EGD）是诊断BE的唯一方法，但由于EGD昂贵，而筛查不 建议在预先诊断的BE患者中检测到非常少的EAC。为了影响 预防和早期发现EAC的挑战是首先开发一种用于筛查的替代方法， 比EGD更便宜和更安全，同时是可接受和可获得的。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以是 在超过90%的BE受试者中从内窥镜刷拭中提取的DNA中检测到。BETRNet补充 该项目旨在将我们发现的BE和EAC的这些表观遗传标记直接翻译到临床上。 用于BE的检测和风险分层的新方法。这个项目源于发现甲基化 基因，具有用作BE或EAC的检测生物标志物的潜力。本项目： 1)使用一种新的非内镜远端食管取样方法来确定 甲基化标记作为BE的检测标记; 2)确定一组异常甲基化基因是否与高度发育不良相关， EAC可以在食管刷检或非内窥镜远端食管样本中检测到， 风险分层策略; 该补充项目的目的显然是在降低死亡率方面产生重大的转化影响， 通过EAC制定一个方便的无创筛查方案。

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.