携带BRCA1/2致病性突变的汉族健康女性乳腺癌发病风险评估

BRCA1 and BRCA2 mutation is currently considered as one of breast cancer risk factors. Women with different type and location of BRCA1/2 mutation may have different risk of breast cancer. Our previous work has shown that not only the morbidity and age of onset of Chinese breast cancer is different from the west, we also found a large number of Chinese-specific mutation of BRCA1/2. Accurately evaluate the risk of breast cancer in high-risk populations can promote the prevention and early diagnosis of breast cancer,and play an important role to reduce the morbidity and mortality of breast cancer.This project is based on our previous work the BRCA1/2 gene entire coding region sequencing study. The aim of this project is to find out breast cancer risk factors in the Chinese Han women with a family history of breast cancer and their age-specific cumulative risk by detect familial breast cancer patients and their first degree female relatives of BRCA1/2 status. The risk evaluation results may further guide prevention, early diagnosis and treatment of Chinese Han women.

BRCA1和BRCA2基因致病性突变是目前公认的预测乳腺癌发病风险的重要因素。其突变率及突变位点对发病风险有影响。中国乳腺癌不仅在发病率、发病年龄异于西方，本课题组的前期工作表明中国乳腺癌在BRCA1/2突变率及突变位点也与西方有较大差异。精准的预测乳腺癌高危人群的发病风险能推动乳腺癌的预防和早诊，具有降低乳腺癌发病率和死亡率的重要作用。本项目基于国内较大宗的家族性乳腺癌BRCA1/2基因突变全编码区测序检测，检测家族性乳癌患者及其一级女性亲属的BRCA1/2突变情况，结合中国汉族女性乳腺癌患者的家族史等个人信息、临床病理资料，用统计学方法筛选出在有乳腺癌家族史的中国汉族妇女中有意义的乳腺癌风险因子，明确有乳腺癌家族史的中国健康汉族妇女在不同BRCA1/2基因状态下乳腺癌发病的年龄累积风险，从而更好的指导中国汉族妇女预防、早诊和治疗乳腺癌。

中国女性乳腺癌患者中BRCA1/2基因突变携带者约占5%。然而中国女性BRCA1/2基因突变携带者的乳腺癌发病风险依然未知。本研究的目的就是评估中国女性BRCA1/2基因突变携带者的年龄累积乳腺癌发病风险。本研究涉及1816名未经家族史等信息筛选的中国女性乳腺癌患者及其5549名女性一级亲属。所有先证者都筛查过BRCA1/2基因突变。通过用kin cohort方法比较BRCA1/2基因携带者和非携带者的女性一级亲属的乳腺癌发生率得出BRCA1/2突变携带者的年龄累积风险。在1816名先证者中，有125人携带了BRCA1/2基因致病性突变（携带BRCA1的70人，携带BRCA2的55人）。BRCA1/2突变携带者女性一级亲属发生乳腺癌的概率高于非携带者的女性一级亲属（BRCA1是3.7倍，BRCA2是4.4倍）。对于BRCA1突变携带者来说，至70岁时的发生乳腺癌的年龄累积风险是37.9%（95%CI，24.1%-54.4%），对于BRCA2突变携带者来说是36.5%（95%CI，26.7%-51.8%）。我们的研究表明中国女性BRCA1/2基因突变携带者至70岁时发生乳腺癌的风险较高。因此，中国女性BRCA1/2基因突变携带者应进行遗传咨询，密切监测及采取个体化的预防。