Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Beijing Cancer Hospital & Institute, Peking University Cancer Hospital, Beijing 100142, People's Republic of China.
Breast Cancer Res Treat. 2012 Apr;132(2):421-8. doi: 10.1007/s10549-011-1596-x. Epub 2011 May 26.
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.
虽然有一些研究调查了中国有家族性乳腺癌的女性中 BRCA1/2 基因的种系突变，但其中许多研究的样本量相对较小。在这项研究中，我们通过聚合酶链反应-测序分析，在中国北方的一个有家族性乳腺癌的 409 名中国女性队列中筛选了 BRCA1/2 基因的种系突变。在该队列中发现了 43 个 BRCA1/2 基因的有害突变，包括 17 个新突变和 6 个复发突变。BRCA1 和 BRCA2 突变的频率分别为 3.9%（16/409）和 6.6%（27/409）；BRCA2 的突变率是 BRCA1 的 1.7 倍。该队列中 BRCA1/2 的总突变率为 10.5%；然而，在 78 名肿瘤诊断年龄在 40 岁或之前的有家族性乳腺癌患者中，BRCA1/2 基因的突变率为 23.0%。在该队列中，BRCA1 携带者（42.8 岁）和 BRCA2 携带者（45.1 岁）的乳腺癌诊断年龄均小于非携带者（51.0 岁）（P=0.005；P=0.01）。此外，BRCA1 携带者和 BRCA2 携带者均比非携带者更有可能表现出三阴性乳腺癌（ER-、PgR-和 HER2-）（BRCA1 携带者与非携带者相比，69.2%比 23.0%，P=0.001；BRCA2 携带者与非携带者相比，45.8%比 23.0%，P=0.01）。我们的研究表明，中国有家族性乳腺癌的 BRCA1/2 突变谱和特征具有一些独特的特征，并且肿瘤诊断年龄在 40 岁或之前的中国有家族性乳腺癌女性是进行 BRCA1/2 检测的合适候选者。
