Whole Exome Approaches for Esophageal Adenocarcinoma Susceptibility Genes

Barrett食管是大多数食管腺癌的前体， 食管胃交界腺癌这些疾病与胃食管癌密切相关 倒流因此，内镜检查被推荐用于慢性胃肠道反流症状的评估。 内镜监测，在那些确定与巴雷特食管，发现癌症在早期 阶段然而，这些癌症中的绝大多数发生在那些先前未确诊的巴雷特氏症患者中。 这些人士当中，接近半数没有胃食管反流症的征状。 遗传危险因素的识别将有助于更好地理解遗传性疾病的分子发病机制。 这些疾病和更有针对性的筛选家庭成员。我们的研究表明， 巴雷特食管及其相关癌症的聚集，我们称之为家族性巴雷特食管 （FBE）。我们已经在八个中心建立了一个调查网络，他们正在积极识别和积累 FBE家族和集中生物库中的淋巴母细胞样细胞系我们的种族隔离分析 提示FBE是常染色体显性遗传易感等位基因的表现。我们 中心假设：

Barrett's esophagus is the precursor of most esophageal adenocarcinomas and a large proportion of esophagogastric junctional adenocarcinomas. These diseases are closely associated with gastroesophageal reflux. Endoscopy is therefore recommended for the evaluation of chronic gastroesophgeal reflux symptoms. Endoscopic surveillance, performed in those identified with Barrett's esophagus, detects cancer at an early stage. However, the large majority of these cancers occur in those with previously undiagnosed Barrett's esophagus and nearly half of these persons have no history of gastroesophageal reflux symptoms. Identification of genetic risk factors would lead to an improved understanding of the molecular pathogenesis of these diseases and more directed screening of family members. Our research has characterized familial aggregation of Barrett's esophagus and its associated cancers, which we term Familial Barrett's Esophagus (FBE). We have developed a network of investigators at eight centers who are actively identifying and accruing FBE families and biobanking lymphoblastoid cell lines in a centralized biorepository. Our segregation analysis of accrued pedigrees suggests that FBE is the manifestation of autosomal dominant susceptibility alleles. Our central hypothesis: