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• W2051781903 abstract "Loss of DNA mismatch repair occurs in a variety of malignancies and is associated with genome-wide instability of microsatellite repeats, a molecular phenotype referred to as microsatellite instability (MSI). MSI is a consistent feature of colorectal and endometrial tumors from patients with hereditary non-polyposis colorectal cancer (HNPCC). Sporadic colorectal and endometrial cancers that exhibit MSI frequently have methylation of the MLH1 promoter. We undertook a detailed family and medical history study to compare family cancer risk for women with MSI-positive and -negative endometrial cancers. The MLH1 promoter methylation status was determined for all cancers. Family histories were developed for 80 probands (40 with MSI-positive and 40 with MSI-negative tumors). The numbers of reported cancers in first- and second-degree relatives of the 2 groups were similar. There was a modest increase in familial cancer clustering for MSI-positive probands. When MSI-positive tumors were subclassified according to MLH1 promoter methylation, a clear association between methylation status and familial cancer risk was evident. Women with MSI-positive endometrial cancers in which the MLH1 promoter was unmethylated had a 7-fold relative risk (RR) of demonstrating familial clustering of cancers [RR 7.07 (95% confidence interval 2.29–21.81)]. The women with MSI-positive, MLH1-unmethylated tumors were significantly younger than the rest of the study population (56.1 years vs. 65.4, p ≤ 0.01). Age of onset and tumor MSI not associated with MLH1 promoter methylation may point to women with a genetic susceptibility to malignancies. © 2002 Wiley-Liss, Inc." @default.
• W2051781903 created "2016-06-24" @default.
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• W2051781903 date "2002-05-24" @default.
• W2051781903 modified "2023-10-17" @default.
• W2051781903 title "MSI in endometrial carcinoma: Absence of MLH1 promoter methylation is associated with increased familial risk for cancers" @default.
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• W2051781903 doi "https://doi.org/10.1002/ijc.10429" @default.
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