BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes
BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes
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DOI：
10.1200/jco.2002.05.121
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发表时间：
2002-06-01
影响因子：
45.3
通讯作者：
Parmigiani, G
中科院分区：
文献类型：
--
作者：
Berry, DA;Iversen, ES;Parmigiani, G
目的：比较BRCA 1和BRCA 2有害突变的基因检测结果与携带此类突变的估计概率;评估基因检测的敏感性;并评估家族性乳腺癌和卵巢癌中其他易感基因的相关性。分析的数据来自六个高-风险遗传咨询诊所和关注来自至少一个成员在BRCA 1和BRCA 2突变测试的家庭的个人。使用BRCAPRO（一种使用孟德尔遗传学和贝叶斯更新的统计模型和软件）对301名个体的乳腺癌和卵巢癌遗传易感性进行预测。模型的预测结果进行了比较，基因testing.Results的结果：在测试的个人，126德系犹太人，三个是男性受试者，243乳腺癌，49卵巢癌，34未受影响，和139测试阳性BRCA 1突变和29 BRCA 2突变。BRCAPRO表现良好：BRCAPRO携带者概率最小的150名先证者（平均29.0%），检测阳性的比例为32.7%;携带者概率最大的151名先证者（平均95.2%），检测阳性的比例为78.8%。基因检测的敏感性估计至少为85%，假阴性包括突变的易感基因迄今unknow.Conclusion：BRCAPRO是一个准确的咨询工具，用于确定携带突变的概率BRCA 1和BRCA 2。BRCA I和BRCA 2的基因检测是高度敏感的，估计有15%的突变缺失。在所研究的人群中，除BRCA 1和BRCA 2以外的乳腺癌易感基因要么不存在，要么罕见，要么与低疾病发生率相关。(C)2002年，美国临床肿瘤学会。
Purpose: To compare genetic test results for deleterious mutations of BRCA1 and BRCA2 with estimated probabilities of carrying such mutations; to assess sensitivity of genetic testing; and to assess the relevance of other susceptibility genes in familial breast and ovarian cancer.Patients and Methods: Data analyzed were from six high-risk genetic counseling clinics and concern individuals from families for which at least one member was tested for mutations at BRCA1 and BRCA2. Predictions of genetic predisposition to breast and ovarian cancer for 301 individuals were made using BRCAPRO, a statistical model and software using Mendelian genetics and Bayesian updating. Model predictions were compared with the results of genetic testing.Results: Among the test individuals, 126 were Ashkenazi Jewish, three were male subjects, 243 had breast cancer, 49 had ovarian cancer, 34 were unaffected, and 139 tested positive for BRCA1 mutations and 29 for BRCA2 mutations. BRCAPRO performed well: for the 150 probands with the smallest BRCAPRO carrier probabilities (average, 29.0%), the proportion testing positive was 32.7%; for the 151 probands with the largest carrier probabilities (average, 95.2%), 78.8% tested positive. Genetic testing sensitivity was estimated to be at least 85%, with false-negatives including mutations of susceptibility genes heretofore unknown.Conclusion: BRCAPRO is an accurate counseling tool for determining the probability of carrying mutations of BRCA1 and BRCA2. Genetic testing for BRCA I and BRCA2 is highly sensitive, missing an estimated 15% of mutations. In the populations studied, breast cancer susceptibility genes other than BRCA1 and BRCA2 either do not exist, are rare, or are associated with low disease penetrance. (C) 2002 by American Society of Clinical Oncology.