{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:04:58Z","timestamp":1782990298519,"version":"3.54.5"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2002,4,19]],"date-time":"2002-04-19T00:00:00Z","timestamp":1019174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2002,6,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Loss of DNA mismatch repair occurs in a variety of malignancies and is associated with genome\u2010wide 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\u2010polyposis 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\u2010positive and \u2010negative endometrial cancers. The MLH1 promoter methylation status was determined for all cancers. Family histories were developed for 80 probands (40 with MSI\u2010positive and 40 with MSI\u2010negative tumors). The numbers of reported cancers in first\u2010 and second\u2010degree relatives of the 2 groups were similar. There was a modest increase in familial cancer clustering for MSI\u2010positive probands. When MSI\u2010positive tumors were subclassified according to MLH1 promoter methylation, a clear association between methylation status and familial cancer risk was evident. Women with MSI\u2010positive endometrial cancers in which the MLH1 promoter was unmethylated had a 7\u2010fold relative risk (RR) of demonstrating familial clustering of cancers [RR 7.07 (95% confidence interval 2.29\u201321.81)]. The women with MSI\u2010positive, MLH1\u2010unmethylated tumors were significantly younger than the rest of the study population (56.1 years <jats:italic>vs.<\/jats:italic> 65.4, <jats:italic>p<\/jats:italic> \u2264 0.01)<jats:italic>.<\/jats:italic> Age of onset and tumor MSI not associated with MLH1 promoter methylation may point to women with a genetic susceptibility to malignancies. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.10429","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T23:29:46Z","timestamp":1030318186000},"page":"697-704","source":"Crossref","is-referenced-by-count":35,"title":["MSI in endometrial carcinoma: Absence of MLH1 promoter methylation is associated with increased familial risk for cancers"],"prefix":"10.1002","volume":"99","author":[{"given":"Alison 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