The E-cadherin gene (CDH1) variants T340A and L599V in gastric and colorectal cancer patients in Korea
The E-cadherin gene (CDH1) variants T340A and L599V in gastric and colorectal cancer patients in Korea
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DOI：
10.1136/gut.47.2.262
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发表时间：
2000-08-01
期刊：
影响因子：
24.5
通讯作者：
Bodmer, WF
中科院分区：
文献类型：
--
作者：
Kim, HC;Wheeler, JMD;Bodmer, WF
前言：在早发性弥漫性胃癌的家族中，已经报道了E-cadherin（CDH 1）的种系突变。最近，突变的CDH 1已被描述在结直肠癌细胞株。AIMS-我们已经调查，如果生殖细胞突变的CDH 1发生在不同群体的韩国胃癌和结直肠癌患者，有和没有一个积极的家族史。方法，我们研究了131例患者和168名正常对照（88韩国和80非韩国）。将患者分为五组：I组，20例有胃癌家族史的患者; II组，26例有胃癌家族史的结直肠癌患者（排除家族性腺瘤性息肉病（FAP）和遗传性非息肉病性结直肠癌（HNPCC）家系）：III组，16例HNPCC患者，未鉴定出hMLH 1和hlMSH 2的生殖系突变; Ⅳ组35例无家族史胃癌患者，Ⅴ组34例无家族史结直肠癌患者。聚合酶链反应，单链构象多态性分析，直接测序，和基因分型确定的变体performed.Results-Several种系变化CDH 1被found. In除了以前描述的多态性，我们发现了三个新的变化，其中两个是错义的变化（T340 A和L599 V）。T340 A存在于组III中的1名患者中，组V中的1名患者中。L599 V存在于组II中的1名患者中，组III中的2名患者中，组IV中的1名患者中。T340 A在正常对照中未发现，而L599 V在88名韩国对照中的两名中存在。具有这些变体的患者可能似乎具有具有阳性家族史的早发性癌症的倾向，尽管频率差异没有达到统计学显著性。基因分型结果表明，这些变异可能有一个共同的起源，特别是T340A.Conclusion，我们已经描述了两个新的错义生殖系变异在不同群体的韩国胃肠道癌患者的CDH 1。需要进一步的工作来评估这些变异是否会增加胃肠道癌的风险。
Introduction-Germline mutations in E-cadherin (CDH1) have been reported in families with early onset, diffuse gastric cancer. More recently, mutations in CDH1 have been described in colorectal cancer cell lines.Aims-We have investigated if germline mutations in CDH1 occur among different groups of Korean gastric and colorectal cancer patients, with and without a positive family history.Methods-We studied 131 patients and 168 normal controls (88 Korean and 80 non-Korean). Patients were divided into five groups: group I, 20 gastric cancer patients with a family history; group II, 26 colorectal cancer patients with a family history of gastric cancer (those from familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) kindred were excluded); group III, 16 HNPCC patients without identified germline mutations in hMLH1 and hlMSH2; group IV 35 gastric cancer patients without a family history; and group V, 34 colorectal cancer patients without a family history. Polymerase chain reaction, single strand conformational polymorphism analysis, direct sequencing, and genotyping for identified variants were performed.Results-Several germline changes in CDH1 were found. In addition to previously described polymorphisms, we found three novel changes, two of which were missense changes (T340A and L599V). T340A was present in one patient in group III and one in group V. L599V was present in one patient in group II, in two in group III, and in one in group IV. T340A was not found in normal controls while L599V was present in two of 88 Korean controls. Patients with these variants may appear to have a tendency to early onset cancer with a positive family history, although differences in frequencies did not reach statistical significance. Genotyping results suggest that these variants might have a common origin, particularly T340A.Conclusion-We have described two new missense germline variants in CDH1 in various groups of Korean gastrointestinal cancer patients. Further work is required to assess if these variants increase the risk of gastrointestinal cancer.