Prevalence and characterization of BRCA1 and BRCA2 germline mutations in Chinese women with familial breast cancer
Prevalence and characterization of BRCA1 and BRCA2 germline mutations in Chinese women with familial breast cancer
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中国家族性乳腺癌女性中 BRCA1 和 BRCA2 种系突变的患病率和特征
DOI：
10.1007/s10549-011-1596-x
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发表时间：
2012-04-01
影响因子：
3.8
通讯作者：
Xie, Yuntao
中科院分区：
文献类型：
--
作者：
Zhang, Juan;Pei, Renguang;Xie, Yuntao
虽然有一些研究调查BRCA 1/2基因在中国女性家族性乳腺癌的生殖系突变，其中许多都是相对较小的样本量。在这项研究中，我们筛选BRCA 1/2基因的生殖细胞突变的409名中国妇女的家族性乳腺癌从中国北方使用PCR测序分析。在该队列中共发现43个BRCA 1/2基因的有害突变，包括17个新突变和6个复发突变。BRCA 1和BRCA 2突变频率分别为3.9%（16/409）和6.6%（27/409），BRCA 2突变率是BRCA 1的1.7倍。BRCA 1/2基因的整体突变率为10.5%，然而，在78例家族性乳腺癌患者中，BRCA 1/2基因的突变率为23.0%，这些患者在40岁或之前被诊断为肿瘤。在该队列中，BRCA 1携带者（42.8岁）和BRCA 2携带者（45.1岁）诊断乳腺癌的平均年龄小于非携带者（51.0岁）（分别为P = 0.005; P = 0.01）。此外，BRCA 1携带者和BRCA 2携带者比非携带者更容易表现出三阴性乳腺癌（ER-、PgR-和HER 2-）（BRCA 1携带者与非携带者，69.2%与23.0%，P = 0.001; BRCA 2携带者与非携带者，45.8%与23.0%，P = 0.01）。我们的研究提示，中国家族性乳腺癌BRCA 1/2基因突变的谱和特征具有一定的特点，40岁或40岁以前确诊的中国家族性乳腺癌患者是BRCA 1/2检测的良好候选者。
Although there are some studies to investigate germline mutations in BRCA1/2 genes in Chinese women with familial breast cancer, many of them suffer relatively small sample size. In this study, we screened germline mutations in BRCA1/2 genes in a cohort of 409 Chinese women with familial breast cancer from north China by using a PCR-sequencing assay. A total of 43 deleterious mutations in BRCA1/2 genes were identified in this cohort, including 17 novel mutations and 6 recurrent mutations. The frequencies of BRCA1 and BRCA2 mutations were 3.9% (16/409) and 6.6% (27/409), respectively; the mutation rate of BRCA2 was 1.7-fold higher than that of BRCA1. The entire mutation rate of BRCA1/2 was 10.5% in this cohort; however, the mutation rate of BRCA1/2 genes was 23.0% in 78 familial breast cancer patients whose tumors were diagnosed at or before the age of 40. The mean age at diagnosis of breast cancer in BRCA1 carriers (42.8 years) and BRCA2 carriers (45.1 years) was younger than non-carriers (51.0 years) in this cohort (P = 0.005; P = 0.01, respectively). In addition, both BRCA1 carriers and BRCA2 carriers were more likely to exhibit triple-negative breast cancer (ER-, PgR-, and HER2-) than non-carriers (BRCA1 carriers vs. non-carriers, 69.2 vs. 23.0%, P = 0.001; BRCA2 carriers vs. non-carriers, 45.8 vs. 23.0%, P = 0.01). Our study suggested that the spectrum and characteristics of BRCA1/2 mutations in Chinese familial breast cancer exhibit some unique features, and Chinese women with familial breast cancer whose tumors are diagnosed at or before the age of 40 are good candidates for BRCA1/2 testing.