中国汉族人群中BRCA1和BRCA2基因突变携带者患乳腺癌风险的研究

背景与目的：BRCA1和BRCA2基因突变携带者终生患乳腺癌和卵巢癌的风险显著增高。通过遗传咨询，突变携带者可采取适当的措施来降低相应肿瘤的发生风险。目前，相关的报道几乎均为白种人，尚缺乏中国人群的资料。该研究旨在探索中国汉族人群中BRCA1和BRCA2基因突变携带者患乳腺癌的风险。方法：回顾20个经基因检测证实携带BRCA1或BRCA2致病性基因突变的汉族乳腺癌高风险家系。利用Kaplan-Meier生存分析法对女性BRCA1/2基因突变携带者单侧乳腺癌及对侧乳腺癌的累积发病风险进行估算。结果：BRCA1和BRCA2基因突变携带者70岁时单侧乳腺癌的累积发病风险(外显率)分别为67.2%(sx 0.100)和76.8%(sx 0.079)。与BRCA1不同的是，BRCA2基因突变携带者70岁后乳腺癌累积发病率继续增加，到80岁时达93.1%。BRCA1/2基因突变携带者对侧乳腺癌10年和20年的累积发病率分别为19.4%(sx 0.089)和50.3%(sx 0.155)。结论：中国汉族人群中BRCA1和BRCA2基因突变携带者具有很高的乳腺癌发病风险。因而对中国高风险人群进行BRCA1/2基因突变检测具有重要临床意义。

Breast cancer risk in BRCA1 and BRCA2 mutation carriers in Chinese Han population

Background and purpose: BRCA1 and BRCA2 mutation carriers have a high lifetime risk of developing breast and ovarian cancer. Through genetic counseling, mutation carriers can take the appropriate measures to reduce such cancer risk. At present, almost all related studies were conducted in Caucasian, while, the studies in Chinese population were rare. This study aimed to investigate the risk of breast cancer in BRCA1 and BRCA2 mutation carriers in Chinese Han population. Methods: Twenty unrelated families with BRCA1 or BRCA2 mutations were reviewed. Kaplan-Meier analyses were used to estimate the cumulative risks of unilateral breast cancer and contralateral breast cancer for female BRCA1 and BRCA2 mutation carriers. Results: Breast cancer risk to 70 years (penetrance) was 67.2% (sx 0.100) for BRCA1 and 76.8% (sx 0.079) for BRCA2, respectively. Different from BRCA1 mutation carriers, the cumulative incidence of breast cancer in BRCA2 mutation carriers remained increasing after 70 years, reaching 93.1% at age 80. The 10- and 20-year risk for contralateral breast cancer was 19.4% (sx 0.089) and 50.3% (sx 0.155) for BRCA1/2 mutation carriers. Conclusion: BRCA1 and BRCA2 mutation carriers in Chinese Han population have a high risk of developing breast cancer. Thus, it has great clinical significance to test mutations in BRCA1/2 genes in Chinesehigh-risk population.