CONSORTIUM TO IDENTIFY GENES FOR BARRETT'S ESOPHAGUS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 食管腺癌、食管胃连接部腺癌及其前体Barrett食管（BE）的家族聚集性称为家族性BE（FBE）。许多研究记录了这些疾病的家族风险增加，提出了一个假设，即BE及其相关癌症的发展可能存在遗传易感性。在这项研究中，使用分离分析的二元性状的实施在S.A.G.E. 6.0.1，我们分析了881个单独确定的家系数据，以确定FBE是否由常见的环境或遗传因素引起，如果是遗传的，则确定FBE的遗传模式。采用似然比检验和Akaike的A信息准则对遗传模型进行了比较。结果表明，随机环境因素和（或）多因素不足以完全解释FBE的家族性，而是存在一种主要类型的遗传分离（P < 10（-10））。一个不完全显性遗传模型与多基因组成部分最适合的数据。在此显性模型中，显性等位基因的估计等位率为0.1005 [95%可信区间（95%CI），0.0587-0.1667]，散发率为0.0012（95%CI，0.0004-0.0042），对应的相对危险度为82.53（95%CI，28.70-237.35）或比值比为91.63（95%CI，32.01-262.29）。这种分离分析提供了流行病学证据，支持一个或多个罕见的常染色体遗传显性易感等位基因在FBE家庭，因此，激发连锁分析。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Familial aggregation of esophageal adenocarcinomas, esophagogastric junction adenocarcinomas, and their precursor Barrett's esophagus (BE) has been termed familial BE (FBE). Numerous studies documenting increased familial risk for these diseases raise the hypothesis that there may be an inherited susceptibility to the development of BE and its associated cancers. In this study, using segregation analysis for a binary trait as implemented in S.A.G.E. 6.0.1, we analyzed data on 881 singly ascertained pedigrees to determine whether FBE is caused by a common environmental or genetic agent and, if genetic, to identify the mode of inheritance of FBE. The inheritance models were compared by likelihood ratio tests and Akaike's A Information Criterion. Results indicated that random environmental and/or multifactorial components were insufficient to fully explain the familial nature of FBE, but rather, there is segregation of a major type transmitted from one generation to the next (P < 10(-10)). An incompletely dominant inheritance model together with a polygenic component fits the data best. For this dominant model, the estimated penetrance of the dominant allele is 0.1005 [95% confidence interval (95% CI), 0.0587-0.1667] and the sporadic rate is 0.0012 (95% CI, 0.0004-0.0042), corresponding to a relative risk of 82.53 (95% CI, 28.70-237.35) or odds ratio of 91.63 (95% CI, 32.01-262.29). This segregation analysis provides epidemiologic evidence in support of one or more rare autosomally inherited dominant susceptibility allele(s) in FBE families and, hence, motivates linkage analyses.