CONSORTIUM TO IDENTIFY GENES FOR BARRETT'S ESOPHAGUS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 家族聚集性食管腺癌、食管胃交界腺癌及其前体Barrett‘s食道(BE)被称为家族性BE(FBE)。大量研究证明，这些疾病的家族风险增加，提出了一种假设，即BE及其相关癌症的发生可能存在遗传易感性。在本研究中，我们使用S.A.G.E.6.0.1中对二元性状的分离分析，分析了881个单一确定的家系的数据，以确定FBE是由共同的环境因素还是遗传因素引起的，如果是遗传的，则确定FBE的遗传模式。遗传模型的比较采用似然比检验和Akaike的A信息准则。结果表明，随机的环境和/或多因素成分不足以完全解释FBE的家族性，而是存在从一代传到下一代的主要类型的分离(P&lt；10(-10))。不完全显性遗传模型和多基因成分最符合数据。在该显性模型中，显性等位基因的外显率估计为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)，优势比为91.63(95%CI，32.01~262.29)。这一分离分析提供了流行病学证据，支持FBE家系中一个或多个罕见的常染色体遗传显性易感等位基因(S)，从而促进了连锁分析。

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.