基因测序法在乳腺癌患者BRCA1／2基因突变检测中的应用与风险评估

Application of gene sequencing in detection of BRCA1/2 gene mutations in breast cancer patients and risk assessment

目的探讨武汉女性居民中乳腺癌相关乳腺和卵巢癌易感基因1／2（BRCAl／2）突变分布状况及患乳腺癌的风险程度。方法用简单随机抽样法选择武汉大学人民医院乳腺外科就诊女性患者128例，其中乳腺癌术后58例、乳腺良性疾病70例；女性健康体检者50名。采用基因测序法检测其BRCAl／2基因序列，将检测序列与标准模板序列比对，分析检测区域突变情况。结果乳腺癌组中，11例发生突变，突变率为19．O％（11／58），其中BRCAl基因8例（3例185delAG、5例5382insC），BRCA2基因3例（2例6174delT、1例C5773T）；乳腺良性疾病组中，5例发生突变，突变率为7．1％（5／70），BRCAl基因4例（1例185delAG、3例5382insC），BRCA2基因1例（6174delT）；健康对照组中均未发现突变。乳腺癌组的突变率明显高于乳腺良性疾病组和健康对照组（，值分别为4．05、10．56，P均〈0．05）；乳腺良性疾病组与健康对照组相比，差异无统计学意义（z。=3．73，P〉0．05）。结论武汉女性居民中存在BRCA1基因（185delAG、5382insC）和BRCA2基因（6174delT、C5773T）突变，该基因突变增加了女性患乳腺癌的风险。

Objective To explore the mutation spectrum of breast and ovarian cancer susceptibility gene 1/2 （BRCA1/2） which was related to breast cancer in female residents of Wuhan, and assess the relation of gene mutation and risk of suffering breast cancer. Methods 128 cases of female individuals, including 58 cases of breast cancer after surgery, 70 cases of benign breast disease, and 50 femal healthy volunteers were selected by simple randon sampling from Department of Breast Surgery of Renmin Hospital of Wuhan University. BRCA1/2 gene was sequenced and compared with the standard template sequence to explore the possible mutations. Results In the breast cancer group, mutation emerged in 11 cases and the mutation rate was 19.0% （11/58） , including 8 cases of the BRCA1 geue mutations （3 cases of 185 del AG, 5 case of 5382 ins C） and 3 cases of the BRCA2 gene mutations （2 cases of 6174 del T, 1 case of C5773T） ; in the benign breast disease group, mutation emerged in 5 cases, the mutation rate was 7.1% （5/70） , including 4 cases of the BRCA1 gene mutations （1 case of 185 del AG, 3 cases of 5382 ins C） , and 1 case of the BRCA2 gene mutation （6174 del T）. There was no mutation detected in healthy control group. The mutation rate of the breast eancer group was significantly higher than that of benign breast disease group and healthy control group （X2 = 4.05, 10.56,P 〈 0.05）; However, there was no significant difference between benign breast disease group and healthy control group （X2 = 3.73, P 〉0. 05）. Conclusions The mutation of BRCA1 gene （185 del AG, 5382 ins C） and BRCA2 gene （6174 del T, C5773T） is in the presence of female residents in Wuhan. Furthermore, the mutation in BRCA1/2 gene increases the risk of breast cancer.