新疆多民族地区三阴性乳腺癌BRCA1基因突变分析

摘要

目的：研究新疆多民族地区三阴性乳腺癌( TNBC ) BRCA1基因的突变情况及突变者与未突变者临床、病理组织特征的差异。方法以新疆多民族地区130例TNBC患者为研究对象,从静脉血提取基因组DNA,采用PCR联合直接测序法检测BRCA1基因突变情况。结果130例TNBC患者BRCA1突变率为17．7%(23/130),其中汉族与少数民族 TNBC 患者 BRCA1突变率分别为20．5%(17/83)、12．8%(6/47),差异无统计学意义(χ2=1．856,P=0．869)。130例TNBC患者中发现23例BRCA1突变的19个位点,其中8个为新发现的位点；4个BRCA1基因突变“热点”；此外还发现了9例(6．9%,9/130)致病性突变,5例无义突变,4例移码突变。早发性 TNBC 组 BRCA1突变率28．3%(13/46)高于晚发性TNBC组11．9%(10/84),差异有统计学意义(χ2=5．460,P<0．05)。 BRCA1基因突变组与BRCA1基因未突变组相比,发病年龄早,腋窝淋巴结转移率高, TNM分期晚,差异均有统计学意义( P<0．05)。结论新疆多民族地区TNBC患者BRCA1基因突变率高；突变者与未突变者相比,存在临床病理组织差异。%Objective To analyze the prevalence of BRCA1 mutations in patients with triple negative breast cancer ( TNBC) in multi-ethnic region of Xinjiang and to discuss the difference of clinical and pathological features be-tween patients with BRCA1 gene mutation and without it. Methods BRCA1 mutations in 130 TNBC cases were detected by PCR-DNA sequencing. Genomic DNA was extracted from blood, and BRCA1 mutations were detected n by combined use of PCR and direct sequencing. Results The prevalence of BRCA1 mutations in 130 TNBC cases was 17. 7%(23/130). There was no statistically significant difference in prevalence of BRCA1 mutations between Han(20. 5%,17/83) and minority cases(12. 8%,6/47) (χ2 =1. 856,P=0. 869). There had been 23 cases of BRCA1 mutations with 19 loci in 130 cases of TNBC patients, 8 of which were new loci. 4 BRCA1 gene mutation"hot spots" were found. In addition, 9 cases of pathogenic mutations(6. 9%, 9/130),including 5 cases of nonsense mutations, 4 cases of frameshift mutations. The prevalence of BRCA1 mutations in 46 early onset breast cancer ca-ses was 28. 3%(13/46), which was higher than that in the late onset group (11. 9%,10/84),and the difference was statistically significant(χ2 =5. 460,P<0. 05). Compared with patients without BRCA1 mutations, who with it had earlier age of onset, higher rate of axillary lymph node metastasis and later of TNM stage,the differences were statistically significant ( P <0. 05 ) . Conclusion The prevalence of BRCA1 mutations in patients with TNBC is higher in multi-ethnic region of Xinjiang. Differences exist in clinical and pathological features between patients with BRCA1 gene mutation and without it.