Performances of eight models for predicting mutations were evaluated in 568 families screened for BRCA1 and BRCA2 mutations and stratified by risk level and by clustering of cancer type Each model showed its own performance deficits, often underestimating the likelihood of a mutation in some types of families, while overestimating it for others All models underestimated mutation probability in the low risk (,10%) group and most underestimated it for the moderate risk group (10–40%). In contrast, all models except the Myriad Tables overestimated mutation probabilities in the highest risk group Overall, two of the Mendelian models (Brcapro and a novel model developed for this study) performed better than the others Models that evaluated probabilities separately for each gene (Mendelian models only) attributed an excess of families to BRCA1 compared with BRCA2; this effect was more pronounced for families with hereditary breast cancer This paper shows prospects for substantial improvement of performance, which could be achieved by adjusting the values of the relevant genetic parameters (allele frequencies and cancer penetrances in carriers and non-carriers)
Evaluation of widely used BRCA1/2-mutation-predicting models
BEVILACQUA, GENEROSO;PRESCIUTTINI, SILVANO
2004-01-01
Abstract
Performances of eight models for predicting mutations were evaluated in 568 families screened for BRCA1 and BRCA2 mutations and stratified by risk level and by clustering of cancer type Each model showed its own performance deficits, often underestimating the likelihood of a mutation in some types of families, while overestimating it for others All models underestimated mutation probability in the low risk (,10%) group and most underestimated it for the moderate risk group (10–40%). In contrast, all models except the Myriad Tables overestimated mutation probabilities in the highest risk group Overall, two of the Mendelian models (Brcapro and a novel model developed for this study) performed better than the others Models that evaluated probabilities separately for each gene (Mendelian models only) attributed an excess of families to BRCA1 compared with BRCA2; this effect was more pronounced for families with hereditary breast cancer This paper shows prospects for substantial improvement of performance, which could be achieved by adjusting the values of the relevant genetic parameters (allele frequencies and cancer penetrances in carriers and non-carriers)I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
