Couch F J, DeShano M L, Blackwood M A, Calzone K, Stopfer J, Campeau L, Ganguly A, Rebbeck T, Weber B L
Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
N Engl J Med. 1997 May 15;336(20):1409-15. doi: 10.1056/NEJM199705153362002.
To define the incidence of BRCA1 mutations among patients seen in clinics that evaluate the risk of breast cancer, we analyzed DNA samples from women seen in this setting and constructed probability tables to provide estimates of the likelihood of finding a BRCA1 mutation in individual families.
Clinical information, family histories, and blood for DNA analysis were obtained from 263 women with breast cancer. Conformation-sensitive gel electrophoresis and DNA sequencing were used to identify BRCA1 mutations.
BRCA1 mutations were identified in 16 percent of women with a family history of breast cancer. Only 7 percent of women from families with a history of breast cancer but not ovarian cancer had BRCA1 mutations. The rates were higher among women from families with a history of both breast and ovarian cancer. Among family members, an average age of less than 55 years at the diagnosis of breast cancer, the presence of ovarian cancer, the presence of breast and ovarian cancer in the same woman, and Ashkenazi Jewish ancestry were all associated with an increased risk of detecting a BRCA1 mutation. No association was found between the presence of bilateral breast cancer or the number of breast cancers in a family and the detection of a BRCA1 mutation, or between the position of the mutation in the BRCA1 gene and the presence of ovarian cancer in a family.
Among women with breast cancer and a family history of the disease, the percentage with BRCA1 coding-region mutations is less than the 45 percent predicted by genetic-linkage analysis. These results suggest that even in a referral clinic specializing in screening women from high-risk families, the majority of tests for BRCA1 mutations will be negative and therefore uninformative.
为了确定在评估乳腺癌风险的诊所中就诊的患者中BRCA1基因突变的发生率，我们分析了在此环境下就诊的女性的DNA样本，并构建了概率表，以估计在各个家族中发现BRCA1基因突变的可能性。
从263名乳腺癌女性患者中获取临床信息、家族史和用于DNA分析的血液样本。采用构象敏感凝胶电泳和DNA测序来鉴定BRCA1基因突变。
在有乳腺癌家族史的女性中，16%检测到BRCA1基因突变。在有乳腺癌家族史但无卵巢癌家族史的女性中，只有7%检测到BRCA1基因突变。在有乳腺癌和卵巢癌家族史的女性中，该突变率更高。在家族成员中，乳腺癌诊断时平均年龄小于55岁、存在卵巢癌、同一女性同时存在乳腺癌和卵巢癌以及阿什肯纳兹犹太血统均与检测到BRCA1基因突变的风险增加相关。未发现双侧乳腺癌的存在或家族中乳腺癌的数量与BRCA1基因突变的检测之间存在关联，也未发现BRCA1基因中突变的位置与家族中卵巢癌的存在之间存在关联。
在有乳腺癌家族史的女性中，BRCA1编码区基因突变的比例低于基因连锁分析预测的45%。这些结果表明，即使在专门筛查高危家族女性的转诊诊所中，大多数BRCA1基因突变检测结果也将为阴性，因此无法提供有用信息。
