Models for predicting BRCA1 and BRCA2 mutations in Han Chinese familial breast and/or ovarian cancer patients
Models for predicting BRCA1 and BRCA2 mutations in Han Chinese familial breast and/or ovarian cancer patients
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DOI：
10.1007/s10549-008-9965-9
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发表时间：
2009-02
影响因子：
3.8
通讯作者：
N. Rao;Zhen Hu;Wen-feng Li;Juan Huang;Zhongliang Ma;Bin Zhang;F. Su;Jie Zhou;G. Di;K. Shen;Jiong Wu;Jin‐song Lu;Jian-Min Luo;W. Yuan;Z. Shen;Wei Huang;Z. Shao
中科院分区：
文献类型：
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作者：
N. Rao;Zhen Hu;Wen-feng Li;Juan Huang;Zhongliang Ma;Bin Zhang;F. Su;Jie Zhou;G. Di;K. Shen;Jiong Wu;Jin‐song Lu;Jian-Min Luo;W. Yuan;Z. Shen;Wei Huang;Z. Shao
目的我们的目的是找到一种适当的方法来估计癌症家族史是BRCA 1或BRCA 2基因突变导致的可能性。我们还比较了三种不同的方法（沙发，SH-E和BRCApro）建立的方法的性能，以确定一种替代策略的遗传理事会针对指定population.Patients和methodsThe家族史以及个人信息的200无关先证者完成了BRCA 1和BRCA 2突变筛查进行了分析，以评估致病性突变的可能性。通过实证方法建立了模型。该模型的性能进行了验证，在一个单独的患者队列相比，BRCApro.ResultsSeveral因素与突变的单变量分析和logistic模型的设计，以估计的概率为先证者窝藏突变BRCA 1和/或BRCA 2。当使用大于10%的概率阈值时，与其他三种模型相比，所建立的模型实现了最高的准确性，呈现出最高的灵敏度、PPV、NPV和ROC曲线下面积。经验模型显示了更好的ROC曲线相比，BRCApro在verification cohol.ConclusionA概率模型针对汉族人群应该是一个有用的工具，在特定的种族遗传咨询。其预测BRCA 2突变携带者的能力有待提高。
PurposeOur aim was to find an appropriate method to estimate the likelihood that a family history of cancer was a result of a mutation in theBRCA1orBRCA2genes. We also compared the performance of the established method with three different methods (Couch, Sh-E and BRCApro) to identify an alternative strategy for genetic council targeted to the specified population.Patients and methodsThe family history as well as individual information of two hundred unrelated probands who had completedBRCA1andBRCA2mutation screening was analyzed to assess the likelihood of a pathogenic mutation. A model was developed by empirical method. The performance of this model was validated in a separate patient cohort compared with BRCApro.ResultsSeveral factors were associated with mutations in univariate analysis and a logistic model was devised to estimate the probability for a proband of harboring a mutation in BRCA1 and/or BRCA2. Using a greater than 10% probability threshold, the highest accuracy was achieved by the established model when compared to other three models, presenting the highest sensitivity, PPV, NPV and area under ROC curve. The empirical model showed a better ROC curve compared to BRCApro in the verification cohort.ConclusionA probability model targeted to Han Chinese population should be a useful tool in the genetic counseling for the specified ethnic. Its ability to predict BRCA2 mutation carriers needs to be improved.