Evaluation of pathogenetic mutations in breast cancer predisposition genes in population-based studies conducted among Chinese women.
Evaluation of pathogenetic mutations in breast cancer predisposition genes in population-based studies conducted among Chinese women.
复制标题
在中国女性中进行的基于人群的研究中乳腺癌易感基因致病突变的评估。
DOI：
10.1007/s10549-020-05643-0
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发表时间：
2020
影响因子：
3.8
通讯作者：
Zheng,Wei
中科院分区：
文献类型：
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作者：
Zeng,Chenjie;Guo,Xingyi;Wen,Wanqing;Shi,Jiajun;Long,Jirong;Cai,Qiuyin;Shu,Xiao-Ou;Xiang,Yongbin;Zheng,Wei
目的对中国女性乳腺癌易感基因的致病性突变进行研究。为了充分表征这些基因在这一人群中的生殖系突变，我们使用了全外显子组测序数据在一个以人群为基础的病例对照研究进行在Shanghai，China.MethodsWe评估外显子，剪接和拷贝数变异11个已建立和14个候选乳腺癌易感基因在831例浸润性乳腺癌病例和839对照。我们确定了55个致病性变异，包括15个新发现的本study.ResultsApproximately 8%的病例和0.6%的无癌对照携带这些致病性变异（P= 3.05 × 10 - 15）。其中aBRCA 2致病性变异占3.7%，aBRCA 1致病性变异占1.6%，而ATM、CHEK 2、NBN、NF 1、CDH 1、PALB 2、PTEN、TP 53以及BARD 1、BRIP和RAD 51 D等基因致病性变异占2.5%。BRCA 1/2致病性变异的患者更有可能有乳腺癌和激素受体阴性肿瘤的家族史相比，没有致病性variants.ConclusionsThis研究强调了遗传性乳腺癌基因在乳腺癌病因的重要性，在这个未充分研究的人口。与之前在东亚女性中的研究一起，这项研究表明BRCA 2的作用相对于BRCA 1更为突出。这项研究也为在中国妇女中设计具有成本效益的基因检测以进行乳腺癌风险评估和早期发现提供了额外的证据。
PurposeLimited 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.MethodsWe 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.ResultsApproximately 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 aBRCA2 pathogenic variant and 1.6% had aBRCA1pathogenic variant, while 2.5% had a pathogenic variant in other genes includingATM, CHEK2, NBN, NF1, CDH1, PALB2, PTEN, TP53as well asBARD1, BRIP,andRAD51D. Patients withBRCA1/2 pathogenic variants were more likely to have a family history of breast cancer and hormone receptor negative tumors compared with patients without pathogenic variants.ConclusionsThis 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 ofBRCA2compared toBRCA1. This study also provides additional evidence to design cost-efficient genetic testing among Chinese women for risk assessment and early detection of breast cancer.