Capalbo Carlo, Ricevuto Enrico, Vestri Annarita, Sidoni Tina, Buffone Amelia, Cortesi Enrico, Marchetti Paolo, Scambia Giovanni, Tomao Silverio, Rinaldi Christian, Zani Massimo, Ferraro Sergio, Frati Luigi, Screpanti Isabella, Gulino Alberto, Giannini Giuseppe
Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.
Eur J Hum Genet. 2006 Jan;14(1):49-54. doi: 10.1038/sj.ejhg.5201511.
Inherited mutations of the BRCA1/2 genes confer a significantly increased risk for breast and/or ovarian cancer development. Several models were elaborated to help genetic counsellors in selecting individuals with high probability of being mutation carriers. The IC software, a country-customized version of the Brcapro model, was recently shown to be particularly accurate in the prediction of carrier probability status in the Italian population. Here, we used our independent series of 70 breast/ovarian cancer families to analyze the performances of the IC software and compare it to widely used models, such as Brcapro and the Myriad mutation prevalence tables. Analysis of the areas under the receiver operator characteristics (ROC) curves indicated that overall the models performed well. However, the IC software and Myriad tables were more efficient in predicting mutated cases, showing a higher sensitivity (94 and 88%, respectively) and negative predictive value (NPV, 94 and 92%, respectively) compared to Brcapro (sensitivity 71 and NPV 83%). IC software also appeared particularly accurate in the identification of families belonging the low mutation risk group (<10%). Finally, most Brcapro failures occurred in the hereditary breast cancer (HBC) family subset, and in 75% of the cases, the IC software corrected them. Our data suggest that the country-customized implementation operated on the Brcapro software generated a more accurate tool for the prediction of BRCA1/2 gene mutation. Whether the IC or other country-customized models might improve BRCA1/2 mutation prediction also in non-Italian families needs to be further explored.
BRCA1/2基因的遗传性突变会显著增加患乳腺癌和/或卵巢癌的风险。人们构建了多种模型，以帮助遗传咨询师筛选出极有可能是突变携带者的个体。IC软件是Brcapro模型的一个针对不同国家定制的版本，最近研究表明，该软件在预测意大利人群的携带者概率状态方面特别准确。在此，我们使用了由70个乳腺癌/卵巢癌家族组成的独立系列样本，来分析IC软件的性能，并将其与广泛使用的模型（如Brcapro和Myriad突变流行率表）进行比较。对受试者工作特征（ROC）曲线下面积的分析表明，总体而言这些模型表现良好。然而，与Brcapro（敏感性分别为71%和阴性预测值为83%）相比，IC软件和Myriad表在预测突变病例方面更有效，敏感性更高（分别为94%和88%），阴性预测值也更高（分别为94%和92%）。IC软件在识别属于低突变风险组（<10%）的家族方面也显得特别准确。最后，大多数Brcapro预测失败的情况发生在遗传性乳腺癌（HBC）家族子集中，在75%的此类病例中，IC软件纠正了这些错误。我们的数据表明，对Brcapro软件进行的国家定制化改进产生了一个更准确的BRCA1/2基因突变预测工具。IC软件或其他国家定制的模型是否也能改善非意大利家族中BRCA1/2突变的预测，还有待进一步探索。
