Drovdlic C M, Goddard K A B, Chak A, Brock W, Chessler L, King J F, Richter J, Falk G W, Johnston D K, Fisher J L, Grady W M, Lemeshow S, Eng C
Clinical Cancer Genetics Program, The Ohio State University, Columbus, OH 43210, USA.
J Med Genet. 2003 Sep;40(9):651-6. doi: 10.1136/jmg.40.9.651.
Based on reported familial patterns, inheritance of a predisposition of developing Barrett's oesesophagus (BO) and oesophageal adenocarcinoma (OAC) likely follows an autosomal dominant model of most inherited cancer syndromes. oesophagus (BO) and oesophageal adenocarcinoma (OAC) likely follows an autosomal dominant model of most inherited cancer syndromes.
We analysed the phenotypic features of 70 familial BO/OAC families accrued for the purpose of initiating a linkage study to search for genes that contribute to susceptibility for BO/OAC.
Families with young or familial BO/OAC were recruited from participating institutions and self-referral from advertisement.
A total of 70 families (173 affected and 784 unaffected individuals) were recruited into this study. Mean ages of diagnosis of BO and OAC among males were 50.6 and 57.4 years, respectively; among females, 52.1 and 63.5 years, respectively. The standardised incidence ratio (SIR) of cancers other than OAC or oesophagogastric junctional adenocarcinoma (OGJAC), among probands was 0.71. Seventy one percent of the pedigrees have "typical" structures with less than three affected individuals. Power calculations under realistic model assumptions suggest that if genetic heterogeneity is absent or limited, then DNA collection from members of these pedigrees could enable the identification of a novel candidate susceptibility gene for BO/OAC in a genome scan.
This is the largest series of families with BO/OAC yet reported, features of which are consistent with inherited germline predisposition. Further, the SIR of cancers other than OAC/OGJAC was 0.71 among 70 probands, indicating these individuals were not more likely to develop non-OAC cancers.
根据已报道的家族模式，Barrett食管（BO）和食管腺癌（OAC）易感性的遗传可能遵循大多数遗传性癌症综合征的常染色体显性模式。
我们分析了70个家族性BO/OAC家系的表型特征，旨在启动一项连锁研究，以寻找导致BO/OAC易感性的基因。
从参与机构招募患有年轻或家族性BO/OAC的家系，并通过广告招募自荐者。
本研究共招募了70个家系（173名患者和784名未患病个体）。男性中BO和OAC的平均诊断年龄分别为50.6岁和57.4岁；女性中分别为52.1岁和63.5岁。先证者中除OAC或食管胃交界腺癌（OGJAC）以外的其他癌症的标准化发病率（SIR）为0.71。71%的家系具有“典型”结构，受累个体少于三人。在现实模型假设下的功效计算表明，如果不存在或有限度地存在遗传异质性，那么从这些家系成员中收集DNA能够在全基因组扫描中鉴定出一个新的BO/OAC候选易感基因。
这是迄今为止报道的最大系列的BO/OAC家系，其特征与遗传性种系易感性一致。此外，70名先证者中除OAC/OGJAC以外的其他癌症的SIR为0.71，表明这些个体患非OAC癌症的可能性并不更高。
