The Department of Medical Genetics, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Fam Cancer. 2010 Dec;9(4):495-502. doi: 10.1007/s10689-010-9348-3.
A number of models have been developed to predict the probability that a person carries a detectable germline mutation in the BRCA1 or BRCA2 genes. Their relative performance in a clinical setting is variable. To compare the performance characteristics of a web-based BRCA1/BRCA2 gene mutation prediction model: the PENNII model ( www.afcri.upenn.edu/itacc/penn2 ), with studies done previously at our institution using four other models including LAMBDA, BRCAPRO, modified PENNI (Couch) tables, and Myriad II tables collated by Myriad Genetics Laboratories. Proband and family cancer history data were analyzed from 285 probands from unique families (27 Ashkenazi Jewish; 277 female) seen for genetic risk assessment in a multispecialty tertiary care group practice. All probands had clinical testing for BR.CA1 and BRCA2 mutations conducted in the same single commercial laboratory. The performance for PENNII results were assessed by the area under the receiver operating characteristic curve (AUC) of sensitivity versus 1-specificity, as a measure of ranking. The AUCs of the PENNII model were higher for predicting BRCA1 than for BRCA2 (81 versus 72%). The overall AUC was 78.7%. PENN II model for BRCA1/2 prediction performed well in this population with higher AUC compared with our experience using four other models. The ease of use of the PENNII model is compatible with busy clinical practices.
已经开发了许多模型来预测一个人在 BRCA1 或 BRCA2 基因中携带可检测种系突变的概率。它们在临床环境中的相对性能是可变的。为了比较基于网络的 BRCA1/BRCA2 基因突变预测模型 PENNII 模型（www.afcri.upenn.edu/itacc/penn2）与我们之前在机构中使用的四种其他模型（包括 LAMBDA、BRCAPRO、改良 PENNI（Couch）表和 Myriad II 表）的性能特征，对 285 名来自独特家族的先证者（27 名阿什肯纳兹犹太人；277 名女性）的家族癌症史数据进行了分析，这些先证者因遗传风险评估而在一家多专科三级保健组实践中就诊。所有先证者均在同一家商业实验室进行了 BR.CA1 和 BRCA2 突变的临床检测。PENNII 结果的性能通过敏感性与 1-特异性的接收器操作特征曲线（ROC）下面积（AUC）来评估，作为排名的衡量标准。PENNII 模型预测 BRCA1 的 AUC 高于预测 BRCA2（81 对 72%）。总体 AUC 为 78.7%。PENN II 模型在该人群中用于 BRCA1/2 预测的性能良好，与我们使用其他四种模型的经验相比，AUC 更高。PENNII 模型易于使用，与繁忙的临床实践兼容。
