Objective To compare the clinical and histological features and prognosis of patients with ovarian cancer from different genetic background, and to make further understanding of the genetic model of BRCA genes used pedigree analysis. Methods There were 71 patients from 67 independent families enrolled in our study from Apr. 2000 to Jun. 2009 in Peking Union Medical College Hospital. All exons of BRCA1/2 genes were analyzed using denaturing high-performance liquid chromatography(DHPLC) followed by direct sequencing, and clinical features of patients were compared by statistical analysis. Pedigree analysis of two families with BRCA genes mutation were performed. Results The mutation rate of BRCA genes was 28%(20/71). The frequency of BRCA1 and BRCA2 gene mutation was 23%(16/71) and 6%(4/71), respectively (P=0.004). Histology types of patients with and without BRCA genes mutation were different. The onset age between patients with and without BRCA genes mutation was similar (52.6 versus 54.6 years old, P=0.393), and tend to be early-onset breast or ovarian cancer in high-risk group. There was no significant difference of platinum-resistant rate, disease free survival and overall survival rate between patients with and without BRCA genes mutation (all P>0.05). According to the pedigree analysis, up to 100% of female offspring inherited pathogenic mutations, and male offspring could be a mutation carrier. Conclusions The genetic screening and clinical intervention should be performed as early as possible for the members from families at risk of hereditary ovarian cancer. Genetic consulting is important for patients with high-grade papillary serous adenocarcinoma of ovary. It is still unknown that whether the patients with BRCA gene mutations have better prognosis than sporadic ones, and further perspective, randomized controlled trial is still needed.%目的：比较不同遗传背景卵巢上皮性癌（卵巢癌）患者的临床特点、病理学特征及预后，通过家系分析，进一步了解BRCA基因突变的遗传模式。方法选取2000年4月至2009年6月间就诊于北京协和医院的卵巢癌患者，共入选71例卵巢癌患者，采用变性高压液相色谱（DHPLC）联合DNA测序的方法对所有患者外周血BRCA1和BRCA2基因进行全序列检测。分别对携带和未携带BRCA基因突变的患者分析其临床特点、病理类型及预后。选取2个携带BRCA基因突变的家族，对其全部女性成员进行BRCA1和BRCA2基因检测，并进行家系分析。结果71例卵巢癌患者BRCA基因总突变率为28%（20/71），其中BRCA1和BRCA2基因的突变率分别为23%（16/71）和6%（4/71），两者比较，差异有统计学意义（P=0.004）。携带和未携带BRCA基因突变的患者病理类型的构成有差异，携带者95%（19/20）为卵巢浆液性腺癌，85%（17/20）为高级别。发病年龄在携带与未携带者间虽无明显差异（中位发病年龄分别为52.6、54.6岁，P=0.393），但高危家族中第2代的肿瘤发病年龄有早于第1代的趋势，且卵巢癌和乳腺癌均有早发趋势。携带和未携带BRCA基因突变的患者铂类耐药比例、无瘤生存期和总生存率分别比较，差异均无统计学意义（P>0.05）。家系分析显示，女性子代对于BRCA基因致病性突变的继承率很高，甚至可以高达100%；男性成员可以作为突变携带者，且消化道肿瘤高发。结论重视家族史和个人史对肿瘤的预测作用，尽早进行卵巢癌的遗传咨询和筛查工作；对于高级别浆液性卵巢癌患者应重视其遗传背景的咨询。BRCA基因突变相关的卵巢癌患者的化疗敏感性和预后是否优于散发性患者，仍需要基于不同遗传背景的大型随机对照研究加以证实。
展开▼
