Purpose Our aim was to find an appropriate method to estimate the likelihood that a family history of cancer was a result of a mutation
in the
BRCA1 or
BRCA2 genes. We also compared the performance of the established method with three different methods (Couch, Sh-E and BRCApro)
to identify an alternative strategy for genetic council targeted to the specified population.
Patients and methods The family history as well as individual information of two hundred unrelated probands who had completed
BRCA1 and
BRCA2 mutation screening was analyzed to assess the likelihood of a pathogenic mutation. A model was developed by empirical method.
The performance of this model was validated in a separate patient cohort compared with BRCApro.
Results Several factors were associated with mutations in univariate analysis and a logistic model was devised to estimate the probability
for a proband of harboring a mutation in BRCA1 and/or BRCA2. Using a greater than 10% probability threshold, the highest accuracy
was achieved by the established model when compared to other three models, presenting the highest sensitivity, PPV, NPV and
area under ROC curve. The empirical model showed a better ROC curve compared to BRCApro in the verification cohort.
Conclusion A probability model targeted to Han Chinese population should be a useful tool in the genetic counseling for the specified
ethnic. Its ability to predict BRCA2 mutation carriers needs to be improved.
Keywords BRCA1/BRCA2 mutations - Models - Breast cancer
Nan-Yan Rao and Zhen Hu are contributed equally to this work.