Scott R J, McPhillips M, Meldrum C J, Fitzgerald P E, Adams K, Spigelman A D, du Sart D, Tucker K, Kirk J
Discipline of Medical Genetics, Hunter Area Pathology Service, John Hunter Hospital, New Lambton, New South Wales, Australia.
Am J Hum Genet. 2001 Jan;68(1):118-127. doi: 10.1086/316942. Epub 2000 Dec 7.
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.
遗传性非息肉病性结直肠癌（HNPCC）描述了一组不同家族的情况，这些家族共同具有在没有癌前表型的情况下易患结直肠癌的倾向。这种疾病的遗传基础与DNA错配修复相关基因的突变有关。很大一部分家族在两个基因hMSH2和hMLH1中的一个存在变化。在基于阿姆斯特丹标准进行诊断的家族中，约35%似乎不存在DNA错配修复基因突变。在本报告中，我们展示了来自大量HNPCC家族系列的数据，并指出携带hMSH2种系变化的家族与携带hMLH1突变的家族之间存在细微差异。此外，家族的突变阳性组（hMSH2和hMLH1合并）与突变阴性组之间也存在差异。本研究确定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谱。乳腺癌在hMSH2突变阳性组中没有显著过多出现，但在hMLH1突变阳性组和突变阴性组中过多出现。前列腺癌在突变阳性组中没有过多出现，但在突变阴性组中过多出现。在结直肠癌诊断年龄方面，hMSH2突变阳性组和hMLH1突变阳性组之间没有差异，但这两组与突变阴性组之间存在显著差异。
