Zhang LingJiao, Shin Vivian Y, Chai Xinglei, Zhang Alan, Chan Tsun L, Ma Edmond S, Rebbeck Timothy R, Chen Jinbo, Kwong Ava
Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Surgery, the University of Hong Kong, Hong Kong.
Oncotarget. 2018 Feb 2;9(38):25025-25033. doi: 10.18632/oncotarget.24382. eCollection 2018 May 18.
Germline mutations in and () are associated with increased risk of breast and ovarian cancer. The penetrance of breast and ovarian cancer in mutation carriers has been well characterized in Caucasian but not in Asian. Two studies have investigated the breast cancer risk in Asian women with mutations, and no published estimates are available for ovarian cancer. Therefore, we estimated the age-specific cumulative risk of -associated breast and ovarian cancer in Chinese women. From Jan 2007 to Nov 2015, the Hong Kong Hereditary Breast Cancer Family Registry identified 1635 families with hereditary breast-ovarian cancer. Among probands in these families, 66 had mutations, 84 had mutations, and 1,485 tested negative for mutations. Using the female first-degree relatives of these probands, we estimated the risk of breast and ovarian cancer using a modified marginal likelihood approach. Estimates of breast cancer penetrance by age 70 were 53.7% (95% CI 34.5-71.6%) for mutation carriers and 48.3% (95% CI 31.8-68.5%) for . The estimated risk of ovarian cancer by age 70 was 21.5% and 7.3% for Chinese women carrying or mutation respectively. A meta-analysis of available studies in Asian women revealed pooled estimates of breast cancer risk by age 70 of 44.8% (95% CI 33-57.2%) and 40.7% (95% CI 31.3-50.9%) for and mutation carriers respectively. These data suggest that -associated breast cancer risk for Chinese women is similar to that for Caucasian women, although -associated ovarian cancer risks are lower for Chinese women.
BRCA1和BRCA2基因的种系突变与乳腺癌和卵巢癌风险增加相关。BRCA1突变携带者中乳腺癌和卵巢癌的外显率在白种人中已有充分研究，但在亚洲人中尚未明确。两项研究调查了亚洲携带BRCA1突变女性的乳腺癌风险，而关于卵巢癌风险尚无公开估计。因此，我们估计了中国女性中与BRCA1/2相关的乳腺癌和卵巢癌的年龄特异性累积风险。2007年1月至2015年11月，香港遗传性乳腺癌家系登记处识别出1635个遗传性乳腺癌-卵巢癌家系。在这些家系的先证者中，66人携带BRCA1突变，84人携带BRCA2突变，1485人BRCA1/2突变检测为阴性。利用这些先证者的女性一级亲属，我们采用改良的边际似然法估计乳腺癌和卵巢癌风险。BRCA1突变携带者70岁时乳腺癌外显率估计为53.7%（95%CI 34.5 - 71.6%），BRCA2突变携带者为48.3%（95%CI 31.8 - 68.5%）。中国携带BRCA1或BRCA2突变女性70岁时卵巢癌估计风险分别为21.5%和7.3%。对亚洲女性现有研究的荟萃分析显示，BRCA1和BRCA2突变携带者70岁时乳腺癌风险的汇总估计分别为44.8%（95%CI 33 - 57.2%）和40.7%（95%CI 31.3 - 50.9%）。这些数据表明，中国女性中与BRCA1/2相关的乳腺癌风险与白种女性相似，尽管中国女性中与BRCA1/2相关的卵巢癌风险较低。
