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Models for predicting the presence of mutations in the BRCA1 and BRCA2 genes Models for predicting the presence of
deleterious mutations in the BRCA1 and BRCA2 genes are generally
reliable, and can be used in clinical activities. The models that
incorporate knowledge of how the genes are transmitted tend to provide a better discrimination, although that comes at the cost of a
somewhat more extensive data collection.
One important caveat is that none of the models should be used
mechanically by applying a threshold on the probability across all
individuals. The main reason is that carriage probability is only one
of the several considerations thas should enter the decision about
seeking genetic testing.
For a general oncology practice, the BRCAPRO model shows a distinct
advantage in terms of discriminating people who will test positive
from people who will not in the population-based portion of our
study. However, other models such as FHAT and Myriad are easier to
implement and may be preferable for practical reasons, especially in
the context of referring patient from primary care clinics to
counseling clinics, where a more in-depth evaluation of the family
history can be performed.
Looking ahead, some of the models that we studied in our Annals article are undergoing significant improvements. This applies
especially to BRCAPRO, which now is able to incorporate information
about oophorectomy in any family members as well as information on
molecular markers in any affected member, and will soon be extended
to handle pedigrees of arbitrary size. The next step for us will be
to reevaluate the models in the light of these ongoing improvements.
Bibliographic reference:
Giovanni Parmigiani The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA
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