Unknown

Dataset Information

0

Functional variants at the 21q22.3 locus involved in breast cancer progression identified by screening of genome-wide estrogen response elements.


ABSTRACT: INTRODUCTION: Estrogen forms a complex with the estrogen receptor (ER) that binds to estrogen response elements (EREs) in the regulatory region of estrogen-responsive genes and regulates their transcription. Sequence variants in the regulatory regions have the potential to affect the transcription factor-regulatory sequence interaction, resulting in altered expression of target genes. This study explored the association between single-nucleotide polymorphisms (SNPs) within the ERE-associated sequences and breast cancer progression. METHODS: The ERE-associated sequences throughout the whole genome that have been demonstrated to bind ER? in vivo were blasted against online information from SNP data sets and 54 SNPs located adjacent to estrogen-responsive genes were selected for genotyping in two independent cohorts of breast cancer patients: 779 patients in the initial screening stage and another 888 in the validation stage. Deaths due to breast cancer or recurrence of breast cancer were defined as the respective events of interest, and the hazard ratios of individual SNPs were estimated based on the Cox proportional hazards model. Furthermore, functional assays were performed, and information from publicly available genomic data and bioinformatics platforms were used to provide additional evidence for the associations identified in the association analyses. RESULTS: The SNPs at 21q22.3 ERE were significantly associated with overall survival and disease-free survival of patients. Furthermore, these 21q22.3 SNPs (rs2839494 and rs1078272) could affect the binding of this ERE-associated sequence to ER? or Rad21 (an ER? coactivator), respectively, which resulted in a difference in ER?-activated expression of the reporter gene. CONCLUSION: These findings support the idea that functional variants in the ER?-regulating sequence at 21q22.3 are important in determining breast cancer progression.

SUBMITTER: Hsiung CN 

PROVIDER: S-EPMC4303134 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

altmetric image

Publications

Functional variants at the 21q22.3 locus involved in breast cancer progression identified by screening of genome-wide estrogen response elements.

Hsiung Chia-Ni CN   Chu Hou-Wei HW   Huang Yuan-Ling YL   Chou Wen-Cheng WC   Hu Ling-Yueh LY   Hsu Huan-Ming HM   Wu Pei-Ei PE   Hou Ming-Feng MF   Yu Jyh-Cherng JC   Shen Chen-Yang CY  

Breast cancer research : BCR 20141009 5


<h4>Introduction</h4>Estrogen forms a complex with the estrogen receptor (ER) that binds to estrogen response elements (EREs) in the regulatory region of estrogen-responsive genes and regulates their transcription. Sequence variants in the regulatory regions have the potential to affect the transcription factor-regulatory sequence interaction, resulting in altered expression of target genes. This study explored the association between single-nucleotide polymorphisms (SNPs) within the ERE-associa  ...[more]

Similar Datasets

| S-EPMC8122893 | biostudies-literature
| S-EPMC9943666 | biostudies-literature
| S-EPMC2551699 | biostudies-literature
| S-EPMC7968217 | biostudies-literature
| S-EPMC5948839 | biostudies-literature
| S-EPMC55815 | biostudies-literature
| S-EPMC3682469 | biostudies-literature
| S-EPMC5709719 | biostudies-literature
| S-EPMC4832559 | biostudies-literature
| S-EPMC5255586 | biostudies-literature