新疆地区维吾尔族、汉族早发性乳腺癌BRCA1基因突变分析

目的研究新疆地区维、汉两族早发性乳腺癌BRCA1基因突变情况及临床病理特征。方法选取病理确诊的65例（维族35例,汉族30例）早发性乳腺癌标本,运用酶链聚合反应（polymerase chain reaction,PCR）和DNA测序方法检测BRCA1基因突变情况,并结合临床病理因素进行相关分析。结果 65例早发性乳腺癌（发病年龄≤35岁）BRCA1的突变率为21.5%（14/65）,35例维吾尔族早发性乳腺癌BRCA1突变率为34.3%（12/35）,30例汉族早发性乳腺癌BRCA1突变率为6.7%（2/30）。65例早发性乳腺癌BRCA1突变的位点为第2、第10、第18号外显子,共发现14个突变位点,位于Exon10共11个,其中10个可引起氨基酸错义突变,3个无义突变;位于Intron18上的1个拼接点突变。65例早发性乳腺癌中BRCA1基因突变者和未突变者在淋巴结转移状况、P53和Ki-67表达情况、组织学分级方面差异有统计学意义（P〈0.05）。结论疆维地区维族、汉族早发性乳腺癌BRCA1基因突变率差异具有统计学意义（P〈0.05）,突变位点可能是新疆维族早发性乳腺癌的遗传易感性位点,与早发性乳腺癌发病存在关联。BRCA1突变者主要临床表现为淋巴结转移多,P53突变率高、Ki-67蛋白高表达等,提示早发性乳腺癌可能发病早、恶性程度高。

The Analysis of the Mutation of BRCA1 Gene of the Uygur and Han Nationality Women with the Early-Onset Breast Cancer in Xinjiang Area

Objective To analysis the mutation of BRCA1 gene of the Uygur and Han nationality women with the early-onset breast cancer in Xinjiang area.Methods The The mutation rate of BRCAI of the 65 cases with the pathological diagnosis of early-onset breast cancer（35cases of Uygur,30 cases of Han）were selected in which the correlation analysis was performed through the polymerase chain reaction（PCR）and DNA sequencing to analyze the mutation of BRCA1 gene and the clinical pathological factors.Results 1）65patients with early-onset breast cancer（age≤35years）was 21.5% mutation rate of BRCA1（14/65）.And the mutation rate 35 cases of Uygur early-onset breast cancer BRCA1 was 34.3%（12/35）that 30 cases of Han early-onset breast cancer BRCA1 was 6.7%（2/30）.2）In 65 patients with early-onset breast adenocarcinoma,the BRCA1 mutation loci were detected 14 in the second,tenth,and eighteenth exons,11 mutations were found in Exon 10.There were 10 of the BRCA1 mutation loci which can cause amino acid missense mutations,3nonsense mutations and 1splicing point mutation in Intron 18.3）65patients with early-onset breast cancer had mutations of BRCA1 gene were statistically different from nonmutation patients（P〈0.05）in the lymph node metastasis,the expression of Ki-67,P53,and histological grade.Conclusion BRCA1 mutation rate is statistically significant（P〈0.05）in Uygur and Han nationality women with early-onset breast cancer in Xinjiang area,and the mutation may be genetic susceptibility loci in Xinjiang Uygur early-onset breast cancer which is associated with the early-onset breast cancer. The BRCA1 mutations manifestations in clinic are lymph node metastasis,the high P53 mutation rate,the high expression of Ki-67 protein and so on.Therefore it means that early onset breast cancer may be early-onset with the high malignancy.