Peltomäki P, Sistonen P, Mecklin J P, Pylkkänen L, Aaltonen L, Nordling S, Kere J, Järvinen H, Hamilton S R, Petersen G
Department of Medical Genetics, University of Helsinki, Finland.
Cancer Res. 1992 Aug 15;52(16):4530-3.
Hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most common form of hereditary colon cancer. Autosomal dominant inheritance is evident from pedigrees but the genetic basis of the disorder is otherwise unknown. Recently, two genes in 5q21 involved in colon carcinogenesis, APC and MCC, were identified, and APC was shown to be the gene predisposing to familial adenomatous polyposis. To determine if these genes also confer susceptibility to HNPCC we performed linkage analyses in nine affected families. The MCC-APC region could be formally excluded as the locus for HNPCC in seven families. In one family the results were suggestive of exclusion, although they were not conclusive. The remaining family was uninformative. We used two alternative definitions of affected status. Based on haplotypes for MCC and APC the added pairwise logarithm-of-odds score for all nine families was -22.57 at the recombination fraction of 0.00 using more stringent criteria for the HNPCC phenotype and -22.67 for less stringent criteria. In addition to blood DNA samples from living family members, DNA from formaldehyde-fixed archival pathology specimens from decreased individuals contributed to these linkage results.
遗传性非息肉病性结直肠癌（HNPCC）是遗传性结肠癌最常见的形式。系谱显示其为常染色体显性遗传，但该疾病的遗传基础尚不明确。最近，在5q21中发现了两个与结肠癌发生相关的基因，即APC和MCC，并且APC被证明是导致家族性腺瘤性息肉病的基因。为了确定这些基因是否也会使个体易患HNPCC，我们对9个患病家族进行了连锁分析。在7个家族中，MCC - APC区域可被正式排除为HNPCC的基因座。在一个家族中，结果提示可能被排除，尽管并不确凿。剩下的一个家族无信息价值。我们使用了两种不同的患病状态定义。基于MCC和APC的单倍型，对于所有9个家族，在重组率为0.00时，使用更严格的HNPCC表型标准，增加的成对对数优势分数为 - 22.57，使用不太严格的标准时为 -
