乳腺癌BRCA1、BRCA2基因突变的检测及临床意义

The clinical significance of BRCA1 and BRCA2 gene mutations in breast cancer

目的分析乳腺癌BRCA1、BRCA2基因突变的检测方法、结果及临床价值。方法选择200例乳腺癌高危女性,采用高通量基因测序法检测BRCA1、BRCA2基因。比较检测结果与乳腺癌筛查结果一致性。分析BRCA1/2基因突变携带者与非携带者乳腺癌诊断年龄差异。评估在一级女性亲属中携带BRCA1/2突变的乳腺癌相关性风险。用kin-cohort设计评估BRCA1/2突变女性携带者乳腺癌风险。结果共发现14例(7%)BRCA1/2的致病突变,BRCA1、BRCA2突变分别为8个、6个。其中6个(42.86%)的BRCA突变为新型突变;BRCA1/2突变携带者被诊断出患有乳腺癌明显比非携带者年轻(P<0.05)。23例研究对象的亲属中发生乳腺癌,BRCA1突变携带者、BRCA2突变携带者和非携带者的乳腺癌发病率分别为10.42%、12.50%和2.49%,BRCA突变携带者的女性一级亲属患乳腺癌的风险明显高于非携带者的亲属。BRCA突变基因携带者40岁、50岁、60岁、70岁时的乳腺癌风险分别为1.7%、10.3%、28.4%、37.4%。结论乳腺癌BRCA1、BRCA2基因突变有助于乳腺癌高危人群筛查,携带者的乳腺癌发生风险要高于非携带者。

Objective To analyze the detection methods,results and clinical significance of BRCA1 and BRCA2 gene mutations in breast cancer.Methods 200 women at high risk of breast cancer were selected in the study.BRCA1/2 gene was detected by high-throughput gene sequencing.And the consistency between the results of breast cancer screening and the results of breast cancer screening were compared.The diagnostic age of breast cancer between BRCA1/2 gene mutation carriers and non-carriers were analyzed.And the risk of breast cancer with BRCA1/2 mutation in first-degree female relatives were assessed.Kin-cohort design was used to assess breast cancer risk in female carriers with BRCA1 and BRCA2 mutations.Results A total of 14(7%)BRCA1/2 mutations were found,including 8 BRCA1 mutations and 6 BRCA2 mutations.Six of the BRCA mutations(42.86%)were new mutations.The BRCA1/2 mutation carriers were diagnosed as having breast cancer significantly younger than non-carriers(P<0.05).23 cases of breast cancer occurred in the relatives of subjects.The incidence of breast cancer in BRCA1 mutation carriers,BRCA2 mutation carriers and non-carriers was 10.42%,12.50%and 3.76%,respectively.The risk of breast cancer in female first-degree relatives of BRCA mutation carriers was significantly higher than that in non-carriers.The risk of breast cancer was 1.7%,10.3%,28.4%and 37.4%for BRCA mutation carriers at 40,50,60 and 70 years old.Conclusion BRCA1 or BRCA2 mutations in breast cancer are helpful for screening of high-risk breast cancer patients.The risk of breast cancer in carriers is higher than that in non-carriers.