110例维吾尔族及汉族乳腺癌中BRCA1基因突变及P53蛋白表达的研究

目的研究维吾尔族及汉族乳腺癌患者BRCA1基因突变及P53蛋白的表达。方法选取70例维吾尔族和40例汉族乳腺癌根治标本,对照组为32例维汉族乳腺良性病变(纤维腺病及纤维腺瘤)及乳腺癌旁非癌组织;运用PCR-SSCP和DNA序列测定的方法检测BRCA1基因突变及Evision二步法检测P53蛋白的表达。结果(1)110例维吾尔族及汉族乳腺癌中发现BRCA1突变的14个新位点。(2)110例维吾尔族及汉族乳腺癌BRCA1的突变率为10%,其中22例维吾尔族早发性乳腺癌(≤35岁)BRCA1突变率为31.82%,高于维吾尔族晚发性乳腺癌(P<0.01)。(3)110例维吾尔族及汉族乳腺癌中发现11例BRCA1基因核苷酸多态性位点。(4)BRCA1基因突变相关性乳腺癌中P53蛋白阳性表达率高于对照组,其淋巴结转移率高于对照组,其发病年龄小于对照组(P<0.01)。结论BRCA1基因突变与新疆维吾尔族早发性乳腺癌密切相关,且BRCA1突变相关性乳腺癌具有P53阳性率高、发病年龄趋于年轻化、淋巴结转移率高的趋势,这些特点有可能为基因检测前的筛选提供参考依据。

A STUDY OF BRCA1 MUTATION AND P53 EXPRESSION IN 110 CASES OF UIGUR AND HAN WOMEN WITH BREAST CANCER

Objective To study the frequency and significance of BRCA1 mutation and the expression of P53 protein in Uigur and Han women with breast cancer in Xinjiang.Methods By using single strand conformational polymorphism(SSCP) and DNA sequencing,BRCA1 mutation was detected in 70 cases of Uigur and 40 cases of Han women with breast cancer and 32 cases of benign breast diseases or non-tumor tissue next to carcinoma.The expression of P53 protein was detected immunohistochemically by Envision method in the 110 cases of breast cancer.Results(1) 14 new loci of BRCA1 mutation were detected firstly in 110 cases of Uigur and Han women with breast cancer.(2)BRCA1 mutation was 10% in the 110 cases.The frequency of BRCA1 mutation in 22 cases of Uigur women with early onset breast cancer was higher than that in the late onset group.(3)There were BRCA1 gene polymorphisms in 11 of 110 sporadic breast cancer patients.(4) Compared with non-BRCA1 mutation cases,BRCA1 mutation cases had higher P53 positive rate and more lymphnode metastases,and were younger.Conclusion The mutation of BRCA1 gene is involved in the carcinogenesis and development of early onset breast cancer in Uigur women.BRCA1 mutation associated breast cancer cases are higher in P53 positive rate and lymph node metastasis,and are younger in the age of onset.