Genotype and phenotype in hereditary nonpolyposis colon cancer: A study of families with different vs. shared predisposing mutations

被引：60

作者：

Peltomäki P. ^{[1
,2
]}

Gao X. ^{[2
]}

Mecklin J.-P. ^{[3
]}

机构：

[1] Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210

[2] Division of Human Cancer Genetics, Ohio State University, Columbus, OH

[3] Department of Surgery, Jyväskylä Central Hospital, Jyväskylä

来源：

Familial Cancer | 2001年 / 1卷 / 1期

基金：

美国国家卫生研究院; 芬兰科学院;

关键词：

DNA mismatch repair; Hereditary non-polyposis colon cancer; MLH1; MSH2; Phenotypic correlations;

D O I：

10.1023/A:1011564720772

中图分类号：

学科分类号：

摘要：

Hereditary nonpolyposis colorectal cancer (HNPCC) is a multi-organ cancer syndrome associated with heritable mutations in DNA mismatch repair genes, particularly MLH1 (MutL Homologue 1) and MSH2 (MutS Homologue 2). We took advantage of the unique characteristics of the Finnish HNPCC families to assess genotype-phenotype correlations in this disorder. We studied 295 mutation carriers (10 mutations in MLH1 and 3 in MSH2) segregating in 55 families. In addition to the comparison of families with different mutations, the enrichment of two MLH1 mutations, one affecting exon 16 (29 families, 186 individuals) and the other one affecting exon 6 (10 families, 45 individuals) allowed the comparison of kindreds with identical predisposing mutations. Extracolonic cancers were more common in MSH2 than in MLH1 mutation carriers, with ratios of 0.48 and 0.64, respectively, of colorectal cancer to all cancers (P = 0.076). Within MLH1, two mutations affecting only the amino terminal portion showed a significant association with late onset of cancer as compared to the remaining mutations. Importantly, families with the MLH1 exon 16 mutation displayed significant variation (P = 0.012) in age at the onset of colon cancer, despite shared predisposition. We conclude that even though characteristics of the inherited mutations may explain part of the observed clinical variation, other factors have a significant impact on HNPCC phenotype determination.

引用

页码：9 / 15

页数：6

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