Demographic and phenotypic features of 70 families segregating Barrett's oesophagus and oesophageal adenocarcinoma
Demographic and phenotypic features of 70 families segregating Barrett's oesophagus and oesophageal adenocarcinoma
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DOI：
10.1136/jmg.40.9.651
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发表时间：
2003-09-01
影响因子：
4
通讯作者：
Eng, C
中科院分区：
文献类型：
--
作者：
Drovdlic, CM;Goddard, KAB;Eng, C
背景资料：Barrett食管（BO）也称为化生柱状衬里食管上皮，被认为是由胃内容物慢性反流的持续修复反应引起的。虽然传统上认为这是一种获得性疾病，涉及几个流行病学风险因素，但现在认识到有遗传成分，并且这可能是常染色体显性的。BO和食管腺癌（OAC）或食管胃交界腺癌（OGJAC）的聚集性已在许多研究中显示。方法：我们调查了一系列BO/OAC家族，以寻找证据表明BO/OAC的一个子集是遗传易感性的结果，并探讨了与迄今为止确定的家族进行连锁研究的可能性。结果：在70个家庭的957名个体中，173人报告了BO或OAC/OGJAC的诊断：101人仅患有BO，52人患有OAC/OGJAC，20人同时患有BO和OAC/OGJAC。受影响的男性有133人，女性有40人，男女比例为3.3：1。此外，124名参与者（12.9%）报告了OAC以外的癌症诊断。其中，15例（受影响）和109例（未受影响）诊断为BO或OAC。在13.9%的未受影响的和8.7%的受影响的individual.Conclusion：它被广泛接受，大多数BO和OAC是散发性的，虽然家族聚集BO和OAC已被确认为至少三十年。环境和生活方式无疑在BO和OAC的发展中起作用，并可能影响假定遗传因素的表达。尽管我们的70位BO先证者并不比正常人更容易患上非OAC/OGJAC癌症，但超过三分之一的人患上了OAC或OGJAC，并且可能继续发展其他癌症。我们打算继续招募并启动正式的连锁研究，以确定致病基因。
Background: Barrett's oesophagus (BO) also termed metaplastic columnar lined oesophageal epithelium, is believed to result from a continual reparative response to chronic reflux of gastric contents. Although traditionally considered to be an acquired disorder, with several epidemiological risk factors involved, it is now recognised that there is a genetic component, and that this is likely to be autosomal dominant. Clustering of BO and of oesophageal adenocarcinoma (OAC) or oesophagogastric junctional adenocarcinoma (OGJAC) has been shown in a number of studies.Methods: We investigated a large series of BO/OAC families to find evidence that a subset of BO/OAC is the result of a hereditary predisposition, and explored the potential of performing a linkage study with the families identified to date.Results: Of 957 individuals in 70 families, 173 had a reported diagnosis of BO or OAC/OGJAC: 101 had BO only, 52 had OAC/OGJAC, and 20 had both BO and OAC/OGJAC. There were 133 affected males and 40 affected females, a male: female ratio of 3.3:1. In addition, 124 participants (12.9%) had a reported diagnosis of cancer other than OAC. Of these, 15 did ( affected) and 109 did not ( unaffected) have a diagnosis of BO or OAC. A cancer other than OAC was found in 13.9% of unaffected and 8.7% of affected individuals.Conclusion: It is widely accepted that the majority of BO and OAC are sporadic, although familial clustering of BO and OAC has been recognised for at least three decades. Environment and lifestyle undoubtedly play a role in development of BO and OAC, and may affect the penetrance of the putative inherited factor. Although our 70 BO probands were not more likely to develop non-OAC/OGJAC cancers than normal, over a third had developed either OAC or OGJAC, and might have gone on to develop others. We intend to continue recruitment and initiate formal linkage studies to identify the causative gene(s).