A functional variant rs4442975 modulating FOXA1-binding affinity does not influence the risk or progression of breast cancer in Chinese Han population
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Yi Zhang1,2, Yan Li2, Shaojie Jiang3, Wei Chen1,4, Jiao Lou1, Juntao Ke1, Jiaoyuan Li1, Ying Zhu1, Yajie Gong1, Yang Yang1, Jianbo Tian1, Xiating Peng1, Danyi Zou1, Jing Gong1, Jiang Chang1, Xiaoping Miao1, Rong Zhong1
1Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health (Incubation), Ministry of Education Key Laboratory of Environment & Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
2Department of Preventive Medicine, School of Public Health, Zunyi Medical University, Zunyi, Guizhou, China
3Department of Gastroenterology, Jing Zhou Central Hospital, Jingzhou, China
4Zhuhai Center for Chronic Disease Control, Zhuhai, China
Rong Zhong, email: [email protected]
Xiaoping Miao, email: [email protected]
Keywords: breast cancer, FOXA1, genetic variants, susceptibility, case-control study
Received: August 20, 2016 Accepted: October 19, 2016 Published: November 07, 2016
The DNA-binding protein FOXA1 has been shown to regulate nearly all estrogen receptor-chromatin interactions, thereby influencing target gene expression levels in breast cancer (BC) cells. Recently, the rs4442975 T-allele, which disrupts the recruitment of FOXA1 and interacts with the IGFBP5 promoter, was associated to BC susceptibility in a European population. We conducted a hospital-based case-control study that included 1227 cases and 1285 controls to explore the potential association between rs4442975 and BC risk in Chinese Han population, and the effect of this SNP on BC progression was also observed in cases. No significant associations between rs4442975 and BC risk were observed under any genetic models, with an odds ratio of 0.96 (95% confidence interval = 0.81-1.15) under the additive model. When stratified based on estrogen or progesterone receptor expression, smoking or drinking habits, or menopausal status, similar negative associations were observed for all subgroups. No significant associations were observed between rs4442975 and traditional progression factors such as tumor size, nodal status, distant metastasis, or TNM staging. These results reveal that rs4442975 may not confer a risk of BC occurrence or progression in the Chinese Han population, which indicates a distinct association related to genetic heterogeneity across ethnic populations.
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