Assessing the predictive accuracy of hMLH1 and hMSH2 mutation probability models
| Autor: | Kory W. Jasperson, Jeffrey N. Weitzel, Katrina Lowstuter |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.diagnostic_test
Receiver operating characteristic Models Genetic business.industry Colorectal cancer Genetic counseling Nuclear Proteins Bioinformatics medicine.disease digestive system diseases Human genetics Lynch syndrome Germline mutation MutS Homolog 2 Protein Mutation (genetic algorithm) Mutation medicine Humans business Carrier Proteins MutL Protein Homolog 1 Genetics (clinical) Genetic testing Adaptor Proteins Signal Transducing Probability |
| Zdroj: | Journal of genetic counseling. 15(5) |
| ISSN: | 1059-7700 |
| Popis: | Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by a susceptibility to colorectal and extra-colonic cancers. Several guidelines exist for the identification of families suspected of having HNPCC, however these guidelines lack adequate sensitivity and specificity. In an attempt to improve accuracy for the detection of individuals with HNPCC, the Wijnen pre-test probability model (1998) and Myriad Genetics Laboratory prevalence table (2004) were developed. Here we evaluate the Wijnen model and Myriad table at predicting the presence of a mutation in individuals undergoing genetic testing for HNPCC. Forty-nine patients who had undergone genetic testing for germline mutations in hMLH1 and/or hMSH2 were part of our analysis. Our results revealed that the revised Bethesda guidelines performed with the highest sensitivity for germline mutations (94.4%), however the specificity was low (12.9%). Using a 10.0% mutation probability threshold, the Wijnen model and Myriad table had sensitivities of 55.6 and 60.0%, respectively and specificities of 54.8 and 23.8%, respectively. The Wijnen model and Myriad table were poor predictors of mutation prevalence, which is shown by the areas underneath their corresponding receiver operator characteristic curves (0.616 and 0.400, respectively). The results of this study demonsrate that neither the Wijnen model nor the Myriad table are sensitive or specific enough to be used as the only indication when to offer genetic testing for HNPCC. |
| Databáze: | OpenAIRE |
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