中文摘要：

目的研究中国早发性乳腺癌患者中BRCAl基因致病性突变的发生情况以及家族史在突变携带者识别中的作用。方法研究对象为来自中国4个乳腺癌临床医疗中心的188例早发性乳腺癌病例（发病年龄≤40岁），其中39例（20．1％）有乳腺／卵巢癌家族史。从外周静脉血提取基因组DNA，对BRCAl基因的全部编码区和外显子／内含子拼接区进行PER扩增。其中22例通过单链构象多态方法进行突变初筛，166例用变性高效液相色谱分析进行初筛；对发现的异常片段通过DNA直接测序的方法进行确认。对发现重复出现突变的样本，选取5个与BRCAl基因连锁的标记（D17S855、D17S1322、D17S1323、D17S1326和D17S1327）进行等位基因型分析。结果在15例（8．0％）患者中发现有12个BRCAl基因的致病性突变，其中BRCAl1100delAT和5589del8突变分别在3个和2个患者中发现。在39例同时伴有乳腺／卵巢癌家族史的病例中共发现有9例（23．1％）携带突变。有（无）乳腺癌家族史的早发性乳腺癌病例间BRCAl基因的突变率的差异有统计学意义（P：0．001）。重复出现的突变在所有检测病例中出现的频率为2．7％，在所有检测到的突变中占33．3％。两个来自中国北方的BRCAl1100delAT突变携带病例有相同的等位基因型，而与来自上海地区的此突变携带者的等位基因型在D17S1322位点上有所差异。两例5589del8突变携带者在所检测的5个Silt位点上有完全相同的等位基因型。结论这是到目前为止较大规模的关于中国早发性乳腺癌人群的BRCAl基因突变的研究，有助于增加对中国早发性乳腺癌人群中BRCAl基因致病性突变分布的全面认识。在中国早发性乳腺癌人群中，BRCAl基因致病性突变在肿瘤的发生中有比较重要的意义，尤其在伴有乳腺／卵巢癌家族史病例中该基因突变的意义尤为突出。两个重复出现的突变可能在中?

英文摘要：

Objectives To investigate the role of disease-associated germ line mutations in BRCA1 gene among Chinese early-onset breast cancer patients. Methods A total of 188 early-onset breast cancer patients, who were diagnosed with breast cancer before 41-year-old, were enrolled from four breast cancer clinical centers in China. Thirty-nine of them （20.7%） also had family history of breast/ovarian cancer. DNA extracted from lymphocytes was amplified by polymerase chain reaction （PCR） for the entire exons and the splicing sites of BRCA1. Twenty-two of the patients were screened by single strand conformation polymorphism （SSCP）, and the other 166 of them were screened by denaturing high performance liquid chromatography （DHPLC）. The abnormal fragments recognized were ascertained by DNA direct sequencing. For those samples with the same recurrent mutations, five BRCA1 -linked markers （D17S855,D17S1322, D17S1323,D17S1326 and D17S1327） were used for the allelotype analysis. Results Twelve disease-associated muta- tions were identified in 15 （8.0%） patients, among whichBRCA1 ll00delAT and 5589de18 were identified in 3 and 2 patients respectively. Nine （23.1%） of them were identified in those with breast/ovarian cancer family history. The difference of BRCA1 mutation frequency between the patients with and without family history was statistically significant （ P = 0.001 ）. Allelotype analysis showed the two BRCA1 5589de18 mutation carriers shared the same allelotype in all the 5 STR sites, and two of the three ll00delAT mutation carriers, who came from the northern China, also shared the same allelotype in all the 5 STR sites, which were different from those of the 5589de18 mutation carriers＇. Conclusion This is a relatively very large scale multi-hospital-based study of BRCA1 mutations in Chinese early-onset breast cancer patients up to now. It seems reasonable to give genetic consultations and genetic test of BRCA1 gene to early-onset breast cancer patients in China, especially for those wit