FOXA1 of regulatory variant associated with risk of breast cancer through allele-specific enhancer in the Chinese population.

Abstract

BACKGROUND:

FOXA1 is a pioneer transcription factor which has been established as a carcinogenic factor and can regulate the expression of downstream target genes in breast cancer. We hypothesized that genetic variants modulating FOXA1 expression might play a role in the risk of breast cancer.

METHODS:

Physical interaction predicted by PreSTIGE analysis and CHIA-PET data integration with cis-expression quantitative trait loci (cis-eQTL) based SNP-FOXA1 analysis were used to identify potentially regulatory variants modulating the expression of FOXA1. Then, we utilized a case-control study consisting of 855 new diagnosed breast cancer cases and 920 controls in the Chinese population to identify breast cancer associated variants. Biological assays were conducted in breast cancer cell lines to illustrate the effects of associated variants on breast cancer risk.

RESULTS:

We identified that rs7160774 G > A variant was associated with lower risk of breast cancer (OR = 0.77, 95% confidence interval = 0.62-0.96, P = 0.022). Biological experiments indicated that rs7160774[A] allele down-regulated the expression of FOXA1 compared to the G allele by influencing transcription factor binding affinity, thus playing an important role in the development of breast cancer.

CONCLUSION:

Our study suggested that the regulatory variant rs7160774 was associated with risk of breast cancer by long-range modulating FOXA1 expression and provided critical insights into pinpoint causal genetic variants.

• Authors: Bin Li, Xiang Cheng, Ying Zhu, Hao Wan, Zequn Lu, Yimin Cai, Wenhui Li, Pengfei Yi, Li Liu, Jiang Chang, Xiaoping Miao, Jianbo Tian, Rong Zhong
• Journal: Breast cancer (Tokyo, Japan) (Breast Cancer) Vol. 29 Issue 2 Pg. 247-259 (Mar 2022) ISSN: 1880-4233 [Electronic] Japan
• PMID: 34635981 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.

Chemical References

• FOXA1 protein, human
• Hepatocyte Nuclear Factor 3-alpha

Topics

• Alleles
• Breast Neoplasms (genetics)
• Case-Control Studies
• Cell Line, Tumor
• China (epidemiology)
• Female
• Gene Expression Regulation, Neoplastic
• Hepatocyte Nuclear Factor 3-alpha (genetics, metabolism)
• Humans
• Polymorphism, Single Nucleotide