Hereditary nonpolyposis colorectal cancer in 95 families: Differences and similarities between mutation-positive and mutation-negative kindreds
Hereditary nonpolyposis colorectal cancer in 95 families: Differences and similarities between mutation-positive and mutation-negative kindreds
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DOI：
10.1086/316942
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发表时间：
2001-01-01
影响因子：
9.8
通讯作者：
Kirk, J
中科院分区：
文献类型：
--
作者：
Scott, RJ;McPhillips, M;Kirk, J
遗传性非息肉病性结直肠癌（HNPCC）描述了一组不同家族的疾病，这些家族在没有癌前表型的情况下具有共同的结直肠癌易感性。这种疾病的遗传基础与DNA错配修复相关的基因突变有关。很大一部分家庭在hMSH2和hMLH1两个基因之一中发生了变化。大约35%的家庭，其中诊断是基于阿姆斯特丹标准似乎没有窝藏突变的DNA错配修复基因。在这份报告中，我们提出了一个大系列的家庭与HNPCC的数据，并指出，有微妙的差异家庭之间的海港hMSH2和hMLH1突变的家庭的种系变化。此外，突变阳性组（hMSH2和hMLH1）之间存在差异。合并）的家庭和突变阴性组的家庭。本研究的主要发现主要集中在突变阳性家族和突变阴性家族之间观察到的结肠外疾病概况。乳腺癌在hMSH 2突变阳性组中的比例并不显着过高，但在hMLH 1突变阳性组和突变阴性组中的比例过高。前列腺癌在突变阳性组中并不多见，但在突变阴性组中多见。在结直肠癌的诊断年龄方面，hMSH2突变阳性组与hMLH1突变阳性组之间没有差异，但这两组与突变阴性组之间有显著差异。
Hereditary nonpolyposis colorectal cancer (HNPCC) describes the condition of a disparate group of families that have in common a predisposition to colorectal cancer in the absence of a premalignant phenotype. The genetic basis of this disease has been linked to mutations in genes associated with DNA mismatch repair. A large proportion of families harbor changes in one of two genes, hMSH2 and hMLH1. Approximately 35% of families in which the diagnosis is based on the Amsterdam criteria do not appear to harbor mutations in DNA-mismatch-repair genes. In this report we present data from a large series of families with HNPCC and indicate that there are subtle differences between families that harbor germline changes in hMSH2 and families that harbor hMLH1 mutations. Furthermore, there are differences between the mutation-positive group (hMSH2 and hMLH1. combined) of families and the mutation-negative group of families. The major findings identified in this study focus primarily on the extracolonic disease profile observed between the mutation-positive families and the mutation-negative families. Breast cancer was not significantly overrepresented in the hMSH2 mutation-positive group but was overrepresented in the hMLH1 mutation-positive group and in the mutation-negative group. Prostate cancer was not overrepresented in the mutation-positive groups but was overrepresented in the mutation-negative group. In age at diagnosis of colorectal cancer, there was no difference between the hMSH2 mutation-positive group and the hMLH1 mutation-positive group, but there was a significant difference between these two groups and the mutation-negative group.