中国每年新确诊乳腺浸润癌患者大约17万例、死于乳腺癌大约4.5万例。中国女性乳腺癌确诊年龄平均45～55岁，比美国年轻10～15岁。此外，中国人群激素受体阴性乳腺癌的比例也显着高于美国。这些结果共同表明，中美两国的乳腺癌风险因素分布不同，尤其乳腺癌遗传基因，故有必要充分了解中国女性人群的乳腺癌遗传基因致病突变比例及其预测因素。
4月21日，施普林格自然旗下《乳腺癌研究与治疗》在线发表美国范德堡大学英格拉姆癌症中心、上海交通大学医学院附属仁济医院上海市肿瘤研究所的研究报告，对中国女性人群全外显子组测序数据的乳腺癌遗传基因致病突变特征进行了分析。
该人群病例对照研究的831例乳腺浸润癌患者和839例无癌对照者，全部来自1996～1998年和2002～入组的上海乳腺癌研究SBCS-I和SBCS-II以及1996～2000年入组的上海妇女健康研究SWHS，对11种已知乳腺癌遗传基因和14种候选乳腺癌遗传基因的外显子、剪接和拷贝数变异进行分析。
结果，发现致病变异共计55种，包括本研究新发现的15种。大约8%的患者和0.6%的无癌对照者携带这些致病变异（P=3.05×10-15）。
患者与无癌对照者相比，基因致病变异比例：
BRCA2：3.73%比0（P=3×10-10）
BRCA1：1.56%比0.36%（P=0.01）
其他（包括ATM、CHEK2、NBN、NF1、CDH1、PALB2、PTEN、TP53、BARD1、BRIP、RAD51D）：2.53%比0.24%
有、无BRCA致病变异相比，有乳腺癌家族史、激素受体阴性乳腺癌的患者比例显着较高。
因此，该研究结果表明，乳腺癌遗传基因对于该人群的乳腺癌病因学具有重要影响，BRCA2与BRCA1相比，影响更为显着，与欧美人群和非洲人群相反。此外，该研究还为中国女性乳腺癌风险评定和早期发现而开展基因检测的性价比提供了证据。
Breast Cancer Res Treat. Apr 21. [Epub ahead of print]
Evaluation of pathogenetic mutations in breast cancer predisposition genes in population-based studies conducted among Chinese women.
Chenjie Zeng, Xingyi Guo, Wanqing Wen, Jiajun Shi, Jirong Long, Qiuyin Cai, Xiao-Ou Shu, Yongbin Xiang, Wei Zheng.
Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA; Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
PURPOSE: Limited studies have been conducted to evaluate pathogenetic mutations in breast cancer predisposition genes among Chinese women. To fully characterize germline mutations of these genes in this population, we used the whole-exome sequencing data in a population-based case-control study conducted in Shanghai, China.
METHODS: We evaluated exonic, splicing, and copy number variants in 11 established and 14 candidate breast cancer predisposition genes in 831 invasive breast cancer cases and 839 controls. We identified 55 pathogenic variants, including 15 newly identified in this study.
RESULTS: Approximately 8% of the cases and 0.6% of the cancer-free controls carried these pathogenetic variants (P=3.05×10-15). Among cases, 3.7% had a BRCA2 pathogenic variant and 1.6% had a BRCA1 pathogenic variant, while 2.5% had a pathogenic variant in other genes including ATM, CHEK2, NBN, NF1, CDH1, PALB2, PTEN, TP53 as well as BARD1, BRIP, and RAD51D. Patients with BRCA1/2 pathogenic variants were more likely to have a family history of breast cancer and hormone receptor negative tumors compared with patients without pathogenic variants.
CONCLUSIONS: This study highlighted the importance of hereditary breast cancer genes in the breast cancer etiology in this understudied population. Together with previous studies in East Asian women, this study suggested a relatively more prominent role of BRCA2 compared to BRCA1. This study also provides additional evidence to design cost-efficient genetic testing among Chinese women for risk assessment and early detection of breast cancer.
KEYWORDS: Clinical genetic testing, Breast cancer risk, Chinese women, Hereditary breast cancer syndromes
DOI: 10.1007/s10549-020-05643-0
