BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer
BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer
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DOI：
10.1056/nejm199705153362002
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发表时间：
1997-05-15
影响因子：
158.5
通讯作者：
Garber, JE
中科院分区：
文献类型：
--
作者：
Couch, FJ;DeShano, ML;Garber, JE
背景为了确定在评估乳腺癌风险的诊所就诊的患者中BRCA1突变的发生率，我们分析了在这种情况下就诊的女性的DNA样本，并构建了概率表，以提供在单个家庭中发现BRCA1突变的可能性的估计。方法从263名乳腺癌患者中获得临床信息、家族史和血液进行DNA分析。结果有乳腺癌家族史的女性中有16%检测到BRCA1基因突变。在有乳腺癌家族史但没有卵巢癌家族史的女性中，只有7%的人有BRCA1突变。在有乳腺癌和卵巢癌家族史的女性中，这一比例更高。在家庭成员中，确诊乳腺癌的平均年龄不到55岁、卵巢癌的存在、同一妇女中存在乳腺癌和卵巢癌，以及德系犹太血统都与检测到BRCA1突变的风险增加有关。未发现双侧乳腺癌的存在或家族中乳腺癌的数量与BRCA1突变的检测，或BRCA1基因突变的位置与家族中卵巢癌的存在之间没有关联。结论在患有乳腺癌和家族病史的女性中，BRCA1编码区突变的比例低于遗传连锁分析预测的45%。这些结果表明，即使在专门筛查高危家庭女性的转诊诊所，大多数BRCA1突变检测也是阴性的，因此没有提供任何信息。(C)1997年，马萨诸塞州医学会。
Background 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.Methods 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.Results 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 an cancer in a family.Conclusions 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. (C) 1997, Massachusetts Medical Society.