Comprehensive analysis of BRCA1 and BRCA2 germline mutations in a large cohort of 5931 Chinese women with breast cancer
Comprehensive analysis of BRCA1 and BRCA2 germline mutations in a large cohort of 5931 Chinese women with breast cancer
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5931 名中国乳腺癌女性大队列中 BRCA1 和 BRCA2 种系突变的综合分析
DOI：
10.1007/s10549-016-3902-0
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发表时间：
2016-08-01
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;Sun, Jie;Xie, Yuntao
我们确定了BRCA1/2胚系突变在中国乳腺癌患者队列中的患病率和特征。共有5931名未经选择的中国乳腺癌女性参加了这项研究，并接受了BRCA1/2突变检测。其中家族性乳腺癌543例，无乳腺癌家族史的早发性疾病(≤40年)1,033例，散发性乳腺癌4,355例。在这个由5931名患者组成的队列中，总共有232名患者(3.9%)携带BRCA1或BRCA2突变(BRCA1中有110人，BRCA2中有122人)。BRCA1/2突变率在家族性乳腺癌中为16.9%(92/543)，在早发性乳腺癌中为5.2%(54/1033)，在散发性乳腺癌中为2.0%(≤；40岁)。在111例40岁及以前确诊的家族性乳腺癌中，BRCA1/2基因突变率为27.0%。该队列中41.4%的突变是中国人群特有的。在2382例BRCA1和BRCA2基因完全测序的病例中，反复突变占全部突变的44.8%。与非携带者相比，BRCA1和BRCA2突变携带者明显更有可能是早发性和双侧乳腺癌、高级别癌症，并有乳腺癌家族史。BRCA1突变携带者比BRCA2突变携带者和非携带者更有可能患三阴性癌症。我们的数据为应该接受BRCA1/2基因检测的中国乳腺癌女性提供了指南；此外，重复突变占突变的近一半，其中一些是中国女性特有的。
We determined the prevalence and characteristics of BRCA1/2 germline mutations in a large cohort of Chinese women with breast cancer. A total of 5931 unselected Chinese women with breast cancer were enrolled in this study and underwent testing for BRCA1/2 mutations. Of these, 543 patients were familial breast cancer, 1033 were early-onset disease (≤40 years) without family history of breast cancer, and 4355 were sporadic breast cancer. In total, 232 patients (3.9 %) carried a BRCA1 or BRCA2 mutation (110 in BRCA1and 122 in BRCA2) in this cohort of 5931 patients. BRCA1/2 mutation rate was 16.9 % (92/543) in familial breast cancers, 5.2 % (54/1033) in early-onset breast cancers (≤40 years), and 2.0 % in sporadic breast cancers (>40 years), respectively. The BRCA1/2 mutation rate was 27.0 % in 111 familial breast cancers diagnosed at and before the age of 40. 41.4 % of mutations in this cohort were specific for Chinese population. Recurrent mutations accounted for 44.8 % of the entire mutations in 2382 cases that BRCA1 and BRCA2 genes were fully sequenced in this study. Both BRCA1 and BRCA2 mutation carriers were significantly more likely to be early-onset and bilateral breast cancers, high-grade cancer, and to have a family history of breast cancer compared with non-carriers. BRCA1 mutation carriers were more likely to be triple-negative cancer than BRCA2 mutation carriers and non-carriers. Our data provide guidelines for Chinese women with breast cancer who should undergo BRCA1/2 genetic testing; additionally, recurrent mutations account for nearly half of the mutations and some of them are specific for Chinese women.