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

eptember 27 issue of JAMA.

Sining Chen, Ph.D., of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues conducted a study to develop a genetic counseling and risk prediction tool to estimate the probability of carrying a mutation in mismatch repair (MMR; a system within the cell for correcting errors in DNA) genes MLH1, MSH2, or MSH6, and the probability of developing colorectal or endometrial cancer. The researchers developed MMRpro, a model that estimates probability based on family history of colorectal and endometrial cancer. External validation of the MMRpro model was conducted on 279 individuals from 226 clinic-based families in the United States, Canada, and Australia (between 1993-2005). All individuals were screened extensively for MLH1 and MSH2 mutations.

"MMRpro predicted the presence of approximately 129 mutations. This shows a close correspondence (calibration) with the observed 121 mutations (ratio of observed to expected results, 0.94)," the authors write. "This results in higher accuracy than existing alternatives and current clinical guidelines."

"This article introduces MMRpro, a model for prediction of genetic susceptibility in the Lynch syndrome, which makes efficient use of family history and tumor information and provides individualized evaluations. Because model-based prediction algorithms are increasingly used in genetic counseling and prevention activities, MMRpro is a timely tool for identifying and counseling families at risk for the Lynch syndrome and can improve current genetic counseling and early detection practice." (JAMA. 2006;296:1479-1487. Available pre-embargo to the media at www.jamamedia.org.)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.


Editorial: Predicting and Preventing
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Contact: Janet Haley Dubow
617-632-5665
JAMA and Archives Journals
26-Sep-2006


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