Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer patients
Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer patients
复制标题
DOI：
10.1086/301903
复制
发表时间：
1998-07-01
影响因子：
9.8
通讯作者：
Eng, CM
中科院分区：
文献类型：
--
作者：
Fodor, FH;Weston, A;Eng, CM
根据有多发和/或早发病例的乳腺癌家族，BRCA1 或 BRCA2 突变携带者终生患乳腺癌的风险估计可能高达 85%。未选择家族史或其他危险因素的个体的风险是不确定的。我们确定了一系列 268 名患有乳腺癌的匿名德系犹太人女性中常见 BRCA1（185delAG 和 5382insC）和 BRCA2（6174delT）突变的频率，无论家族史或发病年龄如何。通过等位基因特异性寡核苷酸杂交分析 DNA 的三种突变。 8 名患者（3.0%，95% CI 1.5%-5.8%）为 185delAG 突变杂合，2 名患者（0.75%，95% CI 0.20-2.7）为 5382insC 突变杂合，8 名患者（3.0%，95% CI 1.5-5.8）为 6174delT 突变杂合。据计算，BRCA1 185delAG 或 BRCA2, 6174delT 突变的德系犹太人携带者患乳腺癌的终生风险为 36%，大约是一般人群总体风险的三倍（相对风险 2.9，95% CI 1.5-5.8）。对于5382insC突变，由于发现的携带者数量较少，有必要进一步研究。结果与之前基于高风险乳腺癌家族的估计值明显不同，并且与巴尔的摩地区最近一项基于人群的研究得出的较低估计值一致。因此，应重新考虑对未选择乳腺癌家族史的德系犹太妇女进行这些常见突变的症状前筛查和咨询，直到确定与这些突变相关的风险为止，特别是因为早期诊断和预防治疗方式有限。
Based on breast cancer families with multiple and/or early-onset cases, estimates of the lifetime risk of breast cancer in carriers of BRCA1 or BRCA2 mutations may be as high as 85%. The risk for individuals not selected for family history or other risk factors is uncertain.We determined the frequency of the common BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) mutations in a series of 268 anonymous Ashkenazi Jewish women with breast cancer, regardless of family history or age at onset. DNA was analyzed for the three mutations by allele-specific oligonucleotide hybridization. Eight patients (3.0%, 95% confidence interval [CI] 1.5%-5.8%) were heterozygous far the 185delAG mutation, two (0.75%, 95% CI 0.20-2.7) for the 5382insC mutation, and eight (3.0%, 95% CI 1.5-5.8) for the 6174delT mutation. The lifetime risk for breast cancer in Ashkenazi Jewish carriers of the BRCA1 185delAG or BRCA2, 6174delT mutations was calculated to be 36%, approximately three times the overall risk for the general population (relative risk 2.9, 95% CI 1.5-5.8). For the 5382insC mutation, because of the low number of carriers found, further studies are necessary. The results differ markedly from previous estimates based on high-risk breast cancer families and are consistent with lower estimates derived from a recent population-based study in the Baltimore area. Thus, presymptomatic screening and counseling for these common mutations in Ashkenazi Jewish women not selected for family history of breast cancer should be reconsidered until the risk associated with these mutations is firmly established, especially since early diagnostic and preventive-treatment modalities are limited.