Abstract
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.
Highlights
Breast cancer (BC) remains a global public health issue and the most common cancer in females worldwide
We conducted a hospital-based casecontrol study that included 1227 cases and 1285 controls to explore the potential association between rs4442975 and breast cancer (BC) risk in Chinese Han population, and the effect of this single nucleotide polymorphisms (SNPs) on BC progression was observed in cases
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
Summary
Breast cancer (BC) remains a global public health issue and the most common cancer in females worldwide. It was estimated that the morbidity and mortality of BC in Chinese females in 2015 were 26.86/100,000 and 6.95/100,000, respectively [2]. The function of the majority of BC risk-associated SNPs, located in non-coding regions, remains unclear, complicating the search for potential mechanisms underlying those associations [5, 6]. Regulatory mechanisms of risk-associated SNPs identified www.impactjournals.com/oncotarget by GWAS have, to date, been gradually discovered. BC risk-associated SNPs identified by GWAS were enriched in the binding sites for the transcription factors FOXA1 and estrogen receptor 1 (ESR1) [7], which suggested FOXA1 contributes to BC development by regulatory mechanisms related to estrogen receptor (ER) signaling [8, 9]
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