BRCA1 and BRCA2 mutation predictions using the BOADICEA and BRCAPRO models and penetrance estimation in high-risk French-Canadian families.
BRCA1 and BRCA2 mutation predictions using the BOADICEA and BRCAPRO models and penetrance estimation in high-risk French-Canadian families.
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BRCA1和BRCA2突变使用Boadicea和Brcapro模型以及高危法国加拿大家庭中的渗透率估计。
DOI：
10.1186/bcr1365
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发表时间：
2006
影响因子：
7.4
通讯作者：
Easton, DF
中科院分区：
文献类型：
--
作者：
Antoniou, AC;Durocher, F;Smith, P;Simard, J;Easton, DF
一些乳腺癌和卵巢癌的遗传风险模型已经被开发出来，但它们对特定人群的适用性尚未得到评估。我们使用来自法裔加拿大家庭的数据来评估BRCAPRO和BOADICEA模型给出的突变预测。我们还使用该数据集来估计BRCA1和BRCA2突变携带者患乳腺癌和卵巢癌的年龄特异性风险。共有195个有多名乳腺癌或卵巢癌患者的家庭通过INHERIT（乳腺癌易感性跨学科健康研究国际团队）BRCAs研究项目被招募。观察到的BRCA1和BRCA2突变状态与BOADICEA和BRCAPRO模型下预测的携带者概率进行比较。采用Brier评分、属性图和受试者工作特征曲线对模型进行评估。乳腺癌和卵巢癌突变携带者相对于人群风险的对数相对风险通过最大似然估计，使用在计算机程序MENDEL中实现的改进分离分析。25个家族有资格纳入BRCA1外显子分析，27个家族有资格进行BRCA2外显子分析。BOADICEA模型准确地预测了不同家庭群体中BRCA1和BRCA2突变的数量，并且在个体水平上发现携带者和非携带者之间有很好的区别。BRCAPRO过度预测了几乎所有家族群体的突变数量，尤其是BRCA1突变的数量。对于高预测概率，它明显高估了载波频率。然而，它很好地区分了携带者和非携带者。受试者工作特征（ROC）曲线显示BRCAPRO和BOADICEA的敏感性和特异性相似。BRCA1和BRCA2突变携带者患乳腺癌和卵巢癌的风险估计值与先前公布的估计值一致。BOADICEA模型准确地预测了法裔加拿大家庭的携带者概率，并可用于该人群的咨询。外显率估计值与以前的估计值没有显著差异，这表明以前的估计值可能适用于该人群的咨询。
Several genetic risk models for breast and ovarian cancer have been developed, but their applicability to specific populations has not been evaluated. We used data from French-Canadian families to evaluate the mutation predictions given by the BRCAPRO and BOADICEA models. We also used this data set to estimate the age-specific risks for breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers. A total of 195 families with multiple affected individuals with breast or ovarian cancer were recruited through the INHERIT (INterdisciplinary HEalth Research International Team on BReast CAncer susceptibility) BRCAs research program. Observed BRCA1 and BRCA2 mutation status was compared with predicted carrier probabilities under the BOADICEA and BRCAPRO models. The models were assessed using Brier scores, attributes diagrams and receiver operating characteristic curves. Log relative risks for breast and ovarian cancer in mutation carriers versus population risks were estimated by maximum likelihood, using a modified segregation analysis implemented in the computer program MENDEL. Twenty-five families were eligible for inclusion in the BRCA1 penetrance analysis and 27 families were eligible for the BRCA2 penetrance analysis. The BOADICEA model predicted accurately the number of BRCA1 and BRCA2 mutations for the various groups of families, and was found to discriminate well at the individual level between carriers and noncarriers. BRCAPRO over-predicted the number of mutations in almost all groups of families, in particular the number of BRCA1 mutations. It significantly overestimated the carrier frequency for high predicted probabilities. However, it discriminated well between carriers and noncarriers. Receiver operating characteristic (ROC) curves indicate similar sensitivity and specificity for BRCAPRO and BOADICEA. The estimated risks for breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers were consistent with previously published estimates. The BOADICEA model predicts accurately the carrier probabilities in French-Canadian families and may be used for counselling in this population. None of the penetrance estimates was significantly different from previous estimates, suggesting that previous estimates may be appropriate for counselling in this population.
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影响因子：
3.5
作者：
Chappuis, PO;Hamel, N;Foulkes, WD
通讯作者：
Foulkes, WD
影响因子：
4
作者：
Evans, DGR;Eccles, DM;Lalloo, F
通讯作者：
Lalloo, F
影响因子：
9.8
作者：
Parmigiani, G;Berry, DA;Aguilar, O
通讯作者：
Aguilar, O
DOI：
10.1093/jnci/91.11.943
发表时间：
1999-06-02
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Peto, J;Collins, N;Stratton, MR
通讯作者：
Stratton, MR
影响因子：
9.8
作者：
Risch, HA;McLaughlin, JR;Narod, SA
通讯作者：
Narod, SA