Prevalence and spectrum of BRCA germline variants in mainland Chinese familial breast and ovarian cancer patients.
Prevalence and spectrum of BRCA germline variants in mainland Chinese familial breast and ovarian cancer patients.
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DOI：
10.18632/oncotarget.7144
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发表时间：
2016-02-23
期刊：
影响因子：
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通讯作者：
Wang SM
中科院分区：
文献类型：
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作者：
Kim YC;Zhao L;Zhang H;Huang Y;Cui J;Xiao F;Downs B;Wang SM
BRCA 1和BRCA 2的生殖系突变是乳腺癌和卵巢癌最具穿透性的遗传易感性，它们的存在主要是种族特异性的。已在欧洲和北美人群中收集了关于BRCA突变的患病率和谱的全面信息。然而，其他人口缺乏类似的信息，包括中国大陆的人口，尽管其庞大的14亿占世界人口的五分之一。在此，我们进行了广泛的文献分析，以收集从中国大陆家族性乳腺癌和卵巢癌患者中鉴定出的BRCA变体。我们在3，844名中国大陆患者中的409名中观察到137种不同的BRCA 1变异，在3，024名中国大陆患者中的157名中观察到80种不同的BRCA 2变异，估计BRCA 1的患病率为10.6%，BRCA 2的患病率为5.2%。在这些变异中，只有40.3%的BRCA 1和42.5%的BRCA 2被列入当前的乳腺癌信息核心数据库。我们观察到中国患者BRCA 1外显子11 A、11 C、11 D和24以及BRCA 2外显子10的变异频率高于其他人群。BRCA 1中最常见的致病性变异是外显子11 A中的c.981_982delAT，BRCA 2中外显子11B中的c.3195_3198delTAAT和外显子11 E中的c.5576_5579delTTAA; BRCA 1中最常见的新变异是外显子10A中的c.919A>G，BRCA 2中外显子14中的c.7142delC。这些变异都没有与其他人群中的创始者突变重叠。我们的分析表明，中国大陆家族性乳腺癌和卵巢癌患者中BRCA变异的患病率与其他人群相似，但其谱与其他人群有显著差异。
Germline mutations in BRCA1 and BRCA2 are the most penetrating genetic predispositions for breast and ovarian cancer, and their presence is largely ethnic-specific. Comprehensive information about the prevalence and spectrum of BRCA mutations has been collected in European and North American populations. However, similar information is lacking in other populations, including the mainland Chinese population despite its large size of 1.4 billion accounting for one fifth of the world's population. Herein, we performed an extensive literature analysis to collect BRCA variants identified from mainland Chinese familial breast and ovarian cancer patients. We observed 137 distinct BRCA1 variants in 409 of 3,844 and 80 distinct BRCA2 variants in 157 of 3,024 mainland Chinese patients, with an estimated prevalence of 10.6% for BRCA1 and 5.2% for BRCA2. Of these variants, only 40.3% in BRCA1 and 42.5% in BRCA2 are listed in current Breast Cancer Information Core database. We observed higher frequent variation in BRCA1 exons 11A, 11C, 11D, and 24 and BRCA2 exon 10 in Chinese patients than in the patients of other populations. The most common pathogenic variant in BRCA1 wasc.981_982delAT in exon 11A, and in BRCA2 c.3195_3198delTAAT in exon 11B and c.5576_5579delTTAA in exon 11E; the most common novel variant in BRCA1 was c.919A>G in exon 10A, and in BRCA2 c.7142delC in exon 14. None of the variants overlap with the founder mutations in other populations. Our analysis indicates that the prevalence of BRCA variation in mainland Chinese familial breast and ovarian cancer patients is at a level similar to but the spectrum is substantially different from the ones of other populations.