CAJ | 학술논문

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。
목적：탐토신강지구합살극족산발성유선암중 BRCA1화 BRCA2기인적돌변빈솔급분포정황。방법선택2005년1월-2013년10월신강의과대학제일부속의원화부속종류의원수치적래자신강지구적합살극족유선암환자86례（병례조）화합살극족건강녀성70례（대조조），유외주정맥혈제취기인조 DNA，대유선암역감기인1（Breast Carcinoma 1，BRCA1）외현자2、10、18、20화유선암역감기인2（Breast Carcinoma 2，BRCA2）외현자10、11급외현자-내함자병접구진행DNA직접측서，병감정돌변위점。결과병례조화대조조공검측도적18개돌변위점중，rs80357374、rs4987117위미지공능변이，기여균위다태성개변。재병례조화대조조중분별검측도195개화143개변이서렬。병례조 rs1799950、rs1801499、rs1799944적분포빈솔명현고우대조조，차이유통계학의의（P ＜0．05）。재중국인군중상미검측도 rs80357374，Intron18-268위신발돌변위점，단재대조조중균검측도2개기인돌변。량조중휴대4개이상돌변적환자인수점각조휴대자적56．9％、39．6％，차이무통계학의의（P ＞0．05）。BRCA2돌변빈솔고우BRCA1，단2개기인돌변빈솔차이무통계학의의（P ＞0．05）。결론합살극족유선암환자BRCA1화BRCA2돌변빈솔고，차상당일부분수시대상동시휴대다개돌변위점，저가능시합살극족인군적특유유전특정。rs1799950、rs1801499、rs1799944저3개위점가능증가합살극족인군리환유선암적풍험，치득금후진일보연구험증。
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 exon-intron splicing areas were performed through DNA direct sequencing in the peripheral blood samples from 86 Kazakh sporadic breast cancer pa-tients (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 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 differ-ence 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 car-rying more than four mutations accounts for 56.9%,39.6% of carriers in each group,no statistical differ-ences 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 popula-tion.Rs1799950,rs1801499,rs1799944 these three loci may increase the risk of breast cancer,and is worth further research.