Berrino Jacopo, Berrino Franco, Francisci Silvia, Peissel Bernard, Azzollini Jacopo, Pensotti Valeria, Radice Paolo, Pasanisi Patrizia, Manoukian Siranoush
Department of Preventive and Predictive Medicine, Fondazione IRCSS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy.
Fam Cancer. 2015 Mar;14(1):117-28. doi: 10.1007/s10689-014-9766-8.
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.
我们设计了用户友好型的COS软件，旨在提高对携带有害BRCA基因突变家族的概率估计。COS软件类似于广泛使用的基于贝叶斯方法的BRCAPRO软件，但它纳入了对有或无有害突变女性癌症发病率的改进假设，考虑了四代以内的亲属关系，并允许研究人员考虑假设的第三个基因或多基因遗传模型。由于乳腺癌发病率和外显率随代际增加，我们估计了特定出生队列的发病率和外显率曲线。我们估计了384个BRCA1突变家族和229个BRCA2突变家族中的乳腺癌和卵巢癌外显率。我们在436个意大利乳腺癌/卵巢癌家族中测试了COS的性能，其中包括79个BRCA1突变家族和27个BRCA2突变家族。受试者操作特征曲线下面积（AUROC）为84.4%。提供检测的最佳概率阈值为22.9%，敏感性为80.2%，特异性为80.3%。尽管假设差异很大，但COS的结果与BRCAPRO v6.0相似。
