Bu Hualei, Chen Jingying, Li Qingshui, Hou Jianqing, Wei Yuan, Yang Xiaohang, Ma Yana, He Hongsheng, Zhang Youzhong, Kong Beihua
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, China.
Gynecologic Oncology Ward 1, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
J Obstet Gynaecol Res. 2019 Nov;45(11):2267-2274. doi: 10.1111/jog.14090. Epub 2019 Aug 14.
Subjects with germline BRCA1/2 mutations (gBRCAm) have an increased risk of developing breast cancer and ovarian cancer. At present, knowledge of BRCA1/2 mutation frequency in Chinese patients with ovarian cancer is still insufficient, and the detailed clinical information of these patients is poorly understood.
A total of 547 unselected ovarian cancer patients were enrolled, and their gBRCAm status was detected. Clinical characteristics including age, personal and family history, histopathologic diagnosis, carbohydrate antigen 125 (CA-125) level, ascites, Federation International of Gynecology and Obstetrics (FIGO) stage, residual lesions, platinum sensitivity, recurrence interval and survival information were collected. Accurate assessments of disease response were based on the RECIST standard or CA-125 level.
In 547 patients with ovarian cancer, we detected 129 (23.6%) patients with pathogenic mutations, 84 patients with BRCA1 mutations (15.4%) and 45 patients with BRCA2 mutations (8.2%). Twenty-five novel mutations were identified, and the mutation of BRCA1, c.5470_5477del8, was the most common mutation in this study. BRCA1/2 mutations were significantly associated with age; personal and family history; FIGO stage; secondary recurrence interval; sensitivity to platinum in 1st, 2nd and 3rd line treatment; and response to doxorubicin liposomes. Patients with BRCA1/2 mutations showed significant advantages in 3- and 5-year survival rates but no advantage in long-term survival.
BRCA1/2 mutation prevalence in Chinese ovarian cancer patients is higher than the international rate. We recommend BRCA1/2 testing for patients with family histories and personal histories of malignancy and genetic counseling for cancer in healthy people with high-risk family histories.
携带种系BRCA1/2突变（gBRCAm）的受试者患乳腺癌和卵巢癌的风险增加。目前，中国卵巢癌患者中BRCA1/2突变频率的相关知识仍不足，且对这些患者的详细临床信息了解甚少。
共纳入547例未经选择的卵巢癌患者，检测其gBRCAm状态。收集临床特征，包括年龄、个人和家族史、组织病理学诊断、糖类抗原125（CA-125）水平、腹水、国际妇产科联合会（FIGO）分期、残留病灶、铂敏感性、复发间隔和生存信息。基于RECIST标准或CA-125水平对疾病反应进行准确评估。
在547例卵巢癌患者中，我们检测到129例（23.6%）患者存在致病突变，84例患者携带BRCA1突变（15.4%），45例患者携带BRCA2突变（8.2%）。鉴定出25种新突变，BRCA1的c.5470_5477del8突变是本研究中最常见的突变。BRCA1/2突变与年龄、个人和家族史、FIGO分期、二次复发间隔、一线、二线和三线治疗对铂的敏感性以及对阿霉素脂质体的反应显著相关。携带BRCA1/2突变的患者在3年和5年生存率方面显示出显著优势，但在长期生存方面没有优势。
中国卵巢癌患者中BRCA1/2突变患病率高于国际水平。我们建议对有恶性肿瘤家族史和个人史的患者进行BRCA1/2检测，并对有高危家族史的健康人进行癌症遗传咨询。
