Berry Donald A, Iversen Edwin S, Gudbjartsson Daniel F, Hiller Elaine H, Garber Judy E, Peshkin Beth N, Lerman Caryn, Watson Patrice, Lynch Henry T, Hilsenbeck Susan G, Rubinstein Wendy S, Hughes Kevin S, Parmigiani Giovanni
Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA.
J Clin Oncol. 2002 Jun 1;20(11):2701-12. doi: 10.1200/JCO.2002.05.121.
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.
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.
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.
BRCAPRO is an accurate counseling tool for determining the probability of carrying mutations of BRCA1 and BRCA2. Genetic testing for BRCA1 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.
比较BRCA1和BRCA2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；评估其他易感基因在家族性乳腺癌和卵巢癌中的相关性。
分析的数据来自六个高危遗传咨询诊所，涉及至少有一名成员接受BRCA1和BRCA2突变检测的家族中的个体。使用BRCAPRO对301名个体患乳腺癌和卵巢癌的遗传易感性进行预测，BRCAPRO是一种利用孟德尔遗传学和贝叶斯更新的统计模型及软件。将模型预测结果与基因检测结果进行比较。
在检测个体中，126人为阿什肯纳兹犹太人，3人为男性，243人患有乳腺癌，49人患有卵巢癌，34人未患病，139人BRCA1突变检测呈阳性，29人BRCA2突变检测呈阳性。BRCAPRO表现良好：对于BRCAPRO携带者概率最小的150名先证者（平均29.0%），检测呈阳性的比例为32.7%；对于携带者概率最大的151名先证者（平均95.2%），78.8%检测呈阳性。基因检测敏感性估计至少为85%，假阴性包括迄今未知的易感基因突变。
BRCAPRO是确定携带BRCA1和BRCA2突变概率的准确咨询工具。BRCA1和BRCA2的基因检测高度敏感，估计遗漏了15%的突变。在所研究的人群中，除BRCA1和BRCA2外的乳腺癌易感基因要么不存在、很罕见，要么与低疾病外显率相关。
