女性乳腺癌危险因素BRCA1基因突变的观察

BRCA1 gene mutations in females with risk factors for breast cancer

目的检测有危险因素者BRCA1第11外显子的突变率。方法38例有危险因素者,年龄29-71岁,有乳腺癌及卵巢癌家族史18例,其中3例本人患乳腺癌;有其他恶性肿瘤家族史者17例;有良性病变者8例,其中1例本人患宫颈癌。25例无危险因素者为对照组。受检者抽取外周血进行DNA提取,经PCR扩增后测序,与NCBI基因库比对。结果1例乳腺良性病变伴宫颈癌者检出4个碱基的缺失突变。危险因素组与对照组另检出6个相同位点的突变,其中5个位点在危险因素组和对照组突变率分别为65.8%和36.0%,两组间存在显著差异(P<0.05)。结论发生于性器官的恶性肿瘤可能有共同的突变位点,危险因素组突变率显著高于对照组,提示家族性乳腺癌可能与更常见的、低外显率基因变异的综合作用有关。

Objective To detect the BRCA1 exon 11 mutation rate in women with risk factors for breast cancer.Methods Thirtyeight women with risk factors for breast cancer at the age of 29-71 years were enrolled in this study.Of them,18 had a family history of breast and ovarian cancer（including 3 with breast cancer）,17 had a family history of other malignancies;8 had a history of benign disease（including 1 with cervical cancer）.Twenty-five individuals with no risk factor served as a control group.DNA was isolated from peripheral blood samples from the subjects,amplified by PCR and sequenced,then compared with NCBI gene bank.Results Four base deletion mutations were detected in 1 benign breast disease case associated with cervical cancer.Mutations were found at 6 identical sites both in risk factor group and in control group.The mutation rate at 5 out of the 6 sites was 65.8% and 36.0%,respectively,in risk factor group and control group（P0.05）.Conclusion Malignancy occurring in sex organs may have common gene mutation sites.The fact that the mutation rate was significantly higher in risk factor group than in control group suggests that familial breast cancer is related with combined effects of more commonly low penetrance of gene mutations.