Oncotarget

Research Papers:

Genetic evaluation of BRCA1-A complex genes with triple-negative breast cancer susceptibility in Chinese women

Hong Ling, Shan Li, Yang Wu, Yi-Zi Zheng, Feng Qiao, Ling Yao, Zhi-Gang Cao, Fu-Gui Ye, Jiong Wu, Xin Hu, Bin Wang and Zhi-Ming Shao _

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Oncotarget. 2016; 7:9759-9772. https://doi.org/10.18632/oncotarget.7112

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Abstract

Hong Ling1,2,*, Shan Li1,2,*, Yang Wu3,*, Yi-Zi Zheng1,2, Feng Qiao1, Ling Yao1, Zhi-Gang Cao1,2, Fu-Gui Ye1,2, Jiong Wu1,3, Xin Hu1,2, Bin Wang4, Zhi-Ming Shao1,2

1Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China

2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

3Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institute of Medical Microbiology, Shanghai Medical College of Fudan University, Shanghai, China

4Department of Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States

*These authors have contributed equally to this work

Correspondence to:

Zhi-Ming Shao, e-mail: [email protected]

Bin Wang, e-mail: [email protected]

Xin Hu, e-mail: [email protected]

Keywords: BRCA1-A complex, NBA1, triple-negative breast cancer, polymorphism, cancer susceptibility

Received: August 31, 2015     Accepted: January 18, 2016     Published: February 01, 2016

ABSTRACT

Background: The tumor suppressor BRCA1 plays a pivotal role in maintaining genomic stability and tumor suppression. The BRCA1-A complex is required for recruitment of BRCA1 to DNA damage sites, DNA repair and cell cycle checkpoint control. Since germline mutations of BRCA1 often lead to breast tumors that are triple-negative breast cancer (TNBC) type, we aimed to investigate whether genetic deficiency in genes of the BRCA1-A complex is associated with risk to TNBC development.

Results: We found that rs7250266 in the promoter region of NBA1 confers a decreased risk to TNBC development, but not to non-TNBC susceptibility. In addition, the haplotypes containing two polymorphisms rs7250266 and rs2278256 are associated with a lower chance of TNBC development specifically. Our studies also showed that the protective alleles of rs7250266 (C > G) and rs2278256 (T > C) down-regulate promoter activity of NBA1 in mammary epithelial cells.

Methods: We investigated associations between the BRCA1-A complex genes and TNBC developing risk in first case-control study of Chinese Han Women population including 414 patients with TNBC and 354 cancer-free controls. We detected 37 common variants in ABRAXAS, RAP80, BRE, BRCC36 and NBA1/MERIT40 genes encoding the BRCA1-A complex and evaluated their genetic susceptibility to the risk of TNBC. An additional cohort with 652 other types of breast cancer (non-TNBC) cases and 890 controls was used to investigate the associations between TNBC-specific SNPs genotype and non-TNBCs susceptibility.

Conclusions: Genetic variants in NBA1 may be an important genetic determinant of TNBC susceptibility. Further investigation and validation of these SNPs in larger cohorts may facilitate in predication and prevention of TNBC and in counseling individuals for risk of TNBC development.


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