Erschienen in:
01.03.2015 | Original Article
Estimate of the penetrance of BRCA mutation and the COS software for the assessment of BRCA mutation probability
verfasst von:
Jacopo Berrino, Franco Berrino, Silvia Francisci, Bernard Peissel, Jacopo Azzollini, Valeria Pensotti, Paolo Radice, Patrizia Pasanisi, Siranoush Manoukian
Erschienen in:
Familial Cancer
|
Ausgabe 1/2015
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Abstract
We have designed the user-friendly COS software with the intent to improve estimation of the probability of a family carrying a deleterious BRCA gene mutation. The COS software is similar to the widely-used Bayesian-based BRCAPRO software, but it incorporates improved assumptions on cancer incidence in women with and without a deleterious mutation, takes into account relatives up to the fourth degree and allows researchers to consider an hypothetical third gene or a polygenic model of inheritance. Since breast cancer incidence and penetrance increase over generations, we estimated birth-cohort-specific incidence and penetrance curves. We estimated breast and ovarian cancer penetrance in 384 BRCA1 and 229 BRCA2 mutated families. We tested the COS performance in 436 Italian breast/ovarian cancer families including 79 with BRCA1 and 27 with BRCA2 mutations. The area under receiver operator curve (AUROC) was 84.4 %. The best probability threshold for offering the test was 22.9 %, with sensitivity 80.2 % and specificity 80.3 %. Notwithstanding very different assumptions, COS results were similar to BRCAPRO v6.0.