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Prediction models help identify increased risk of gene mutation linked with colorectal cancer

Prediction models that incorporate certain personal and family medical history characteristics can help identify high-risk patients who are likely to have a gene mutation associated with a type of colorectal cancer, according to two studies in the September 27 issue of JAMA.

Lynch syndrome (also called hereditary nonpolyposis colorectal cancer) is the most common hereditary colorectal cancer syndrome in Western countries, accounting for 2 percent to 5 percent of all colorectal cancers (CRCs). Lynch syndrome is primarily associated with mutations in the MLH1 and MSH2 genes. In hereditary breast-ovarian cancer syndrome, multiple models have been developed to predict mutations in the BRCA1 and BRCA2 genes, and these models are widely implemented by health care professionals as they assess their patients' genetic risk. For Lynch syndrome, the relative importance of specific aspects of personal and family medical history remains unclear.

Judith Balmana, M.D., formerly of the Dana-Farber Cancer Institute, Boston, and colleagues obtained data from 1,914 individuals undergoing genetic testing of MLH1 and MSH2 and developed a clinical model, the PREMM1,2 (Prediction of Mutations in MLH1 and MSH2) to predict the presence of mutations in the MLH1 and MSH2 genes based on personal and family medical history. A model was developed in an initial group of 898 individuals and subsequently validated in 1,016 patients.

Overall, 14.5 percent (130/898) of the study individuals were found to have mutations: 6.5 percent had mutations in MLH1 and 8.0 percent had mutations in MSH2. In the validation cohort, the overall prevalence of mutations was 15.3 percent. Mutations were particularly prevalent among probands (a patient who is the initial member of a family to come under study) with 2 or more separate CRCs, endometrial cancer, other Lynch syndromeassociated cancers, and multiple diagnoses. The prevalence of mutations in the probands increased with incre
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Contact: Janet Haley Dubow
617-632-5665
JAMA and Archives Journals
26-Sep-2006


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