100例遗传性乳腺癌胚系基因BRCA1/2突变研究

BRCA1/2 germline mutation in 100 patients with hereditary breast cancer

目的探讨遗传性乳腺癌患者胚系基因BRCA1/2的外显子区域突变情况及其与临床病理特征的关系。方法本研究为回顾性研究。根据纳入和排除标准,选择2014年2月至2016年2月山西省人民医院乳腺外科确诊的100例遗传性乳腺癌患者作为研究对象,采用二代测序技术检测患者胚系基因BRCA1/2突变的情况,并收集其年龄、组织学分级、淋巴结状态以及ER、PR、HER-2状态等临床病理资料。然后,采用Fisher确切概率检验比较BRCA1与BRCA2基因突变类型的差异,并用χ2检验分析BRCA1/2基因突变与乳腺癌患者临床病理特征的关系。结果在100例遗传性乳腺癌患者中,有6例患者携带BRCA1基因突变,11例患者携带BRCA2基因突变。而在6例BRCA1基因突变者中,发生移码突变和无义突变者分别占4/6、2/6;在11例BRCA2基因突变者中,发生移码突变和无义突变者分别占4/11、7/11;2组间比较,基因突变类型的差异无统计学意义(P=0.335)。在组织学分级1、2级的患者中,携带BRCA1、BRCA2基因突变者以及不携带BRCA1/2基因突变者分别占4.4%(4/91)、8.8%(8/91)和86.8%(79/91),而在组织学分级为3级的患者中,携带BRCA1、BRCA2基因突变者及不携带BRCA1/2基因突变者分别占2/9、3/9和4/9,组间比较,差异有统计学意义(χ2=9.398,P=0.007)。在HER-2阴性乳腺癌患者中,携带BRCA1、BRCA2基因突变者及不携带BRCA1/2基因突变者分别占10.7%(6/56)、16.1%(9/56)和73.2%(41/56),而在HER-2阳性乳腺癌患者中,携带BRCA1、BRCA2基因突变者及不携带BRCA1/2基因突变者分别占0(0/44)、4.5%(2/44)和95.5%(42/44),组间比较,差异有统计学意义(χ2=9.072,P=0.007)。结论遗传性乳腺癌患者胚系基因BRCA1/2突变在不同组织学分级、不同HER-2状态的患者间存在差异。本研究在丰富遗传性乳腺癌临床遗传学资料的同时,可能为后期的个体化精准治疗奠定一定的理论依据。

Objective To investigate the mutation status of BRCA1/2 exon region and its relationship with clinicopathological characteristics in hereditary breast cancer patients. Methods This was a retrospective study. According to the inclusion and exclusion criteria,100 patients diagnosed with hereditary breast cancer in the Department of Breast Surgery,Shanxi Provincial People＇s Hospital from February 2004 to February 2006 were enrolled in this study. The mutation status of BRCA1/2 gene was detected by next-generation sequencing.The related clinicopathological data were collected,including age,histological grade,lymph node status,ER,PR and HER-2 expression. The mutation type was compared between BRCA1 and BRCA2 using Fisher＇s exact probability test.The relationship of BRCA1/2 mutation with clinicopathological characteristics was analyzed byχ2 test. Results Six patients carried BRCA1 mutation and 11 patients carried BRCA2 mutation in 100 patient with hereditary breast cancer. In 6 patients with BRCA1 mutation,there were 4 with frameshift mutation and 2 with nonsense mutation. In 11 patients with BRCA2 mutation,there were 4 with frameshift mutation and 7 with nonsense mutation. There was no statistically significant difference between two groups（ P = 0. 335）. In the patients with breast cancer of histological grade 1 and 2,the patients with BRCA1 mutation,BRCA2 mutation and no BRCA1/2 mutation accounted for 4.4%（ 4/91）,8.8%（ 8/91） and 86.8%（ 79/91）,respectively. In the patients with breast cancer of histological grade 3,the patients with BRCA1 mutation,BRCA2 mutation and no BRCA1/2 mutation accounted for 2/9,3/9 and 4/9, respectively. There was statistically significant difference between two groups（ χ2= 9.398,P = 0.007）. In HER-2 negative patients,the proportion of patients with BRCA1 mutation,BRCA2 mutation and no BRCA1/2 mutation was 10.7%（ 6/56）,16.1%（ 9/56） and73.2%（ 41/56）,respectively. In HER-2 positive patients,the proportion of patients with BRCA1 mutation,BRCA2 mutation and no BRCA1/2 mutation was 0（ 0/44）, 4. 5%（ 2/44） and 95. 5%（ 42/44）,respectively. There was statistically significant difference between two groups（ χ2= 9. 072,P = 0.007）.Conclusions There are some differences in the distribution of BRCA1/2 mutation in hereditary breast cancer patients with different histological grades and HER-2 expression. This study increases the clinical genetic data of hereditary breast cancer and provides a theoretical reference for the individualized precision treatment.