A probability model for predicting BRCA1 and BRCA2 mutations in breast andbreast-ovarian cancer families

Germline mutations in BRCA1 and BRCA2 genes predispose to hereditary breast and ovarian cancer. Our aim was to find associations between the clinical characteristics and positive mutation status in 148 breast cancer families in order to predict the probability of finding a BRCA mutation in a family. Several factors were associated with mutations in univariate analysis, whe reas in multivariate analysis (logistic regression with backward selection) only the age of the youngest breast cancer patient and the number of ovari an cancer cases in a family were independent predictors of BRCA mutations. A logistic model was devised to estimate the probability for a family of ha rbouring a mutation in either BRCA1 or BRCA2, Altogether, 63 out of 148 fam ilies (43%) and 28 out of 29 (97%) mutation carrier families obtained proba bilities over 10%. The mean probability was 55% for mutation-positive famil ies and 11% for mutation-negative families. The models by Couch et al (1997 ) and Shattuck-Eidens et al (1997) previously designed for BRCA1 were also tested for their applicability to distinguish carrier families with mutatio ns in either gene. The probability model should be a useful tool in genetic counselling and focusing the mutation analyses, and thus increasing also t he cost-effectiveness of the genetic screening. (C) 2001 Cancer Research Ca mpaign.