目的BRCA1/2基因胚系变异按照风险等级分为5类,其中3类意义未明位点(variants of the uncertain significance,VUS)需要定期复核。探索变异证据的更新对变异分类的影响并指导携带有害VUS位点的患者进行临床诊疗。方法收集971例进行了BRC...目的BRCA1/2基因胚系变异按照风险等级分为5类,其中3类意义未明位点(variants of the uncertain significance,VUS)需要定期复核。探索变异证据的更新对变异分类的影响并指导携带有害VUS位点的患者进行临床诊疗。方法收集971例进行了BRCA1/2基因胚系检测的患者(乳腺或卵巢癌),筛选出VUS位点128个。整合人群频率数据库、疾病数据库、计算机软件预测、共分离证据、等位基因证据及人群队列研究等证据,重新分析这些VUS位点,明确变异分类是否发生改变。结果142例肿瘤患者携带BRCA1/2基因VUS位点,占14.6%(142/971),变异位点数为128个,其中错义突变、同义突变、框内非移码突变和非编码区突变的比例分别为70.3%、4.7%、3.1%、21.9%。重新复核分析发现11.7%(15/128)的VUS位点可降级为2类,疑似良性。结论随着胚系变异相关证据的不断更新,VUS位点经再次复核后变异分类可能会有所改变。展开更多
目的:评估BRCA1/2基因突变状态与卵巢癌患者临床特征的相关性及对预后的影响。方法:选取2017年11月—2022年6月在兰州大学第一医院进行治疗的51例接受BRCA1/2基因检测的卵巢癌患者作为研究对象,根据检测结果分为BRCA1/2突变组(30例)和BR...目的:评估BRCA1/2基因突变状态与卵巢癌患者临床特征的相关性及对预后的影响。方法:选取2017年11月—2022年6月在兰州大学第一医院进行治疗的51例接受BRCA1/2基因检测的卵巢癌患者作为研究对象,根据检测结果分为BRCA1/2突变组(30例)和BRCA1/2正常组(21例)。比较2组患者的临床基线资料、临床病理特征和预后,分析影响BRCA1/2基因突变的卵巢癌患者预后的相关因素。结果:BRCA1/2突变组与BRCA1/2正常组相比,发病年龄、体质量指数(body mass index,BMI)、恶性肿瘤家族史、治疗前糖类抗原125(carbohydrate antigen 125,CA125)及人附睾蛋白4(human epididymis protein 4,HE4)差异均无统计学意义(均P>0.05)。BRCA1/2突变组与BRCA1/2正常组肿瘤分期及淋巴结转移情况比较,差异有统计学意义(P<0.05)。多因素Cox回归分析显示BRCA1/2基因突变不是卵巢癌生存率及无进展生存期的独立预后因素(HR=0.752,95%CI:0.394~1.435,P=0.329)。结论:BRCA1/2基因突变是决定卵巢癌患者临床治疗的重要因素,与肿瘤分期及淋巴结转移情况显著相关,但仍不能确定BRCA1/2基因突变是卵巢癌的独立危险因素。展开更多
Objective:The spectrum and risk of cancer in relatives of BRCA1/2 pathogenic variant carriers in the Chinese population have not been established.Methods:A family history of cancer in 9903 unselected breast cancer pat...Objective:The spectrum and risk of cancer in relatives of BRCA1/2 pathogenic variant carriers in the Chinese population have not been established.Methods:A family history of cancer in 9903 unselected breast cancer patients was retrospectively analyzed.BRCA1/2 status was determined for all patients and relative risks(RRs)were calculated to evaluate cancer risk in relatives of the patients.Results:The incidences of breast cancer in female relatives of BRCA1 carriers,BRCA2 carriers,and non-carriers were 33.0%,32.2%,and 7.7%,respectively.The corresponding incidences of ovarian cancer were 11.5%,2.4%,and 0.5%,respectively.The incidences of pancreatic cancer in male relatives of BRCA1 carriers,BRCA2 carriers,and non-carriers were 1.4%,2.7%,and 0.6%,respectively.The corresponding incidences of prostate cancer were 1.0%,2.1%,and 0.4%,respectively.The risks of breast and ovarian cancers in female relatives of BRCA1 and BRCA2 carriers were significantly higher than female relatives of non-carriers(BRCA1:RR=4.29,P<0.001 and RR=21.95,P<0.001;BRCA2:RR=4.19,P<0.001 and RR=4.65,P<0.001,respectively).Additionally,higher risks of pancreatic and prostate cancers were noted in male relatives of BRCA2 carriers than non-carriers(RR=4.34,P=0.001 and RR=4.86,P=0.001,respectively).Conclusions:Female relatives of BRCA1 and BRCA2 carriers are at increased risk for breast and ovarian cancers,and male relatives of BRCA2 carriers are at increased risk for pancreatic and prostate cancers.展开更多
文摘目的BRCA1/2基因胚系变异按照风险等级分为5类,其中3类意义未明位点(variants of the uncertain significance,VUS)需要定期复核。探索变异证据的更新对变异分类的影响并指导携带有害VUS位点的患者进行临床诊疗。方法收集971例进行了BRCA1/2基因胚系检测的患者(乳腺或卵巢癌),筛选出VUS位点128个。整合人群频率数据库、疾病数据库、计算机软件预测、共分离证据、等位基因证据及人群队列研究等证据,重新分析这些VUS位点,明确变异分类是否发生改变。结果142例肿瘤患者携带BRCA1/2基因VUS位点,占14.6%(142/971),变异位点数为128个,其中错义突变、同义突变、框内非移码突变和非编码区突变的比例分别为70.3%、4.7%、3.1%、21.9%。重新复核分析发现11.7%(15/128)的VUS位点可降级为2类,疑似良性。结论随着胚系变异相关证据的不断更新,VUS位点经再次复核后变异分类可能会有所改变。
文摘目的:评估BRCA1/2基因突变状态与卵巢癌患者临床特征的相关性及对预后的影响。方法:选取2017年11月—2022年6月在兰州大学第一医院进行治疗的51例接受BRCA1/2基因检测的卵巢癌患者作为研究对象,根据检测结果分为BRCA1/2突变组(30例)和BRCA1/2正常组(21例)。比较2组患者的临床基线资料、临床病理特征和预后,分析影响BRCA1/2基因突变的卵巢癌患者预后的相关因素。结果:BRCA1/2突变组与BRCA1/2正常组相比,发病年龄、体质量指数(body mass index,BMI)、恶性肿瘤家族史、治疗前糖类抗原125(carbohydrate antigen 125,CA125)及人附睾蛋白4(human epididymis protein 4,HE4)差异均无统计学意义(均P>0.05)。BRCA1/2突变组与BRCA1/2正常组肿瘤分期及淋巴结转移情况比较,差异有统计学意义(P<0.05)。多因素Cox回归分析显示BRCA1/2基因突变不是卵巢癌生存率及无进展生存期的独立预后因素(HR=0.752,95%CI:0.394~1.435,P=0.329)。结论:BRCA1/2基因突变是决定卵巢癌患者临床治疗的重要因素,与肿瘤分期及淋巴结转移情况显著相关,但仍不能确定BRCA1/2基因突变是卵巢癌的独立危险因素。
基金supported by grants from National Natural Science Foundation of China(Grant Nos.81974422,81772824,and 81802635)。
文摘Objective:The spectrum and risk of cancer in relatives of BRCA1/2 pathogenic variant carriers in the Chinese population have not been established.Methods:A family history of cancer in 9903 unselected breast cancer patients was retrospectively analyzed.BRCA1/2 status was determined for all patients and relative risks(RRs)were calculated to evaluate cancer risk in relatives of the patients.Results:The incidences of breast cancer in female relatives of BRCA1 carriers,BRCA2 carriers,and non-carriers were 33.0%,32.2%,and 7.7%,respectively.The corresponding incidences of ovarian cancer were 11.5%,2.4%,and 0.5%,respectively.The incidences of pancreatic cancer in male relatives of BRCA1 carriers,BRCA2 carriers,and non-carriers were 1.4%,2.7%,and 0.6%,respectively.The corresponding incidences of prostate cancer were 1.0%,2.1%,and 0.4%,respectively.The risks of breast and ovarian cancers in female relatives of BRCA1 and BRCA2 carriers were significantly higher than female relatives of non-carriers(BRCA1:RR=4.29,P<0.001 and RR=21.95,P<0.001;BRCA2:RR=4.19,P<0.001 and RR=4.65,P<0.001,respectively).Additionally,higher risks of pancreatic and prostate cancers were noted in male relatives of BRCA2 carriers than non-carriers(RR=4.34,P=0.001 and RR=4.86,P=0.001,respectively).Conclusions:Female relatives of BRCA1 and BRCA2 carriers are at increased risk for breast and ovarian cancers,and male relatives of BRCA2 carriers are at increased risk for pancreatic and prostate cancers.
