新疆地区哈萨克族乳腺癌患者BRCA1和BRCA2基因的突变分析

目的：探讨新疆地区哈萨克族散发性乳腺癌中 BRCA1和 BRCA2基因的突变频率及分布情况。方法选择2005年1月-2013年10月新疆医科大学第一附属医院和附属肿瘤医院收治的来自新疆地区的哈萨克族乳腺癌患者86例（病例组）和哈萨克族健康女性70例（对照组），由外周静脉血提取基因组 DNA，对乳腺癌易感基因1（Breast Carcinoma 1，BRCA1）外显子2、10、18、20和乳腺癌易感基因2（Breast Carcinoma 2，BRCA2）外显子10、11及外显子-内含子拼接区进行DNA直接测序，并鉴定突变位点。结果病例组和对照组共检测到的18个突变位点中，rs80357374、rs4987117为未知功能变异，其余均为多态性改变。在病例组和对照组中分别检测到195个和143个变异序列。病例组 rs1799950、rs1801499、rs1799944的分布频率明显高于对照组，差异有统计学意义（P ＜0．05）。在中国人群中尚未检测到 rs80357374，Intron18-268为新发突变位点，但在对照组中均检测到2个基因突变。两组中携带4个以上突变的患者人数占各组携带者的56．9％、39．6％，差异无统计学意义（P ＞0．05）。BRCA2突变频率高于BRCA1，但2个基因突变频率差异无统计学意义（P ＞0．05）。结论哈萨克族乳腺癌患者BRCA1和BRCA2突变频率高，且相当一部分受试对象同时携带多个突变位点，这可能是哈萨克族人群的特有遗传特征。rs1799950、rs1801499、rs1799944这3个位点可能增加哈萨克族人群罹患乳腺癌的风险，值得今后进一步研究验证。

Analysis of BRCA1 and BRCA2 gene mutations in Kazakh patients with breast cancer in Xinj iang

Objective To evaluate the frequency and distribution of BRCA1 and BRCA2 gene mutations in Kazakh women diagnosed with sporadic breast cancer in Xinjiang.Methods Mutation screening of BRCA1 gene exon 2,10,18,20 and BRCA2 gene exon 10,11,and exonintron splicing areas were performed through DNA direct sequencing in the peripheral blood samples from 86 Kazakh sporadic breast cancer patients （case group）and 70 Kazakh healthy women （control group）from Xinjiang.Results 18 mutations were detected in the case-control group including the unknown variants of rs80357374,rs4987117 and the rest polymorphisms,all of which are not deleterious mutations.1 9 5 sequence variants in BRCA1/2 gene＆amp;nbsp;were identified in case group,whereas 143 sequence variants in control group.The distribution frequency of rs1799950,rs1801499,rs1799944 in case group is significantly higher than in control group,the difference was statistically significant （P 〈0.05）.Rs80357374 has not been detected in China population,and intron18-268 as new mutations,but both mutations were for healthy women.The number of subjects carrying more than four mutations accounts for 56.9%,39.6% of carriers in each group,no statistical differences in the two groups （P 〉0.05）.Conclusion The higher mutation frequency and quite a few subjects carrying multiple mutations at the same time could be a unique genetic characteristics of Kazakh population.Rs1799950,rs1801499,rs1799944 these three loci may increase the risk of breast cancer,and is worth further research.