HER4 rs1595065 3'UTR Variant is a Possible Risk Factor for HER2 Positivity Among Breast Cancer Patients


Bahareh Moradi 1 , Hossein Tabatabaeian 2 , Samira Sadeghi 2 , Mansoureh Azadeh 1 , Kamran Ghaedi 3 , *


1 Najafabad Branch, Islamic Azad University, Najafabad, Isfahan, Iran

2 Genetics Division, Biology Department, Faculty of Sciences, University of Isfahan, Isfahan, Iran

3 Cellular and Molecular Biology Division, Biology Department, Faculty of Sciences, University of Isfahan, Isfahan, Iran


Thrita: 5 (4); 42195
Published Online: November 18, 2016
Article Type: Research Article
Received: September 10, 2016
Accepted: November 9, 2016




Background: Breast cancer (BC) is the most common neoplasia among females worldwide. Single nucleotide polymorphisms (SNPs) located at the 3? untranslated Region (3?UTR) can alter gene expression pattern through increasing/decreasing microRNAs (miRNAs) binding energy. Human epidermal growth factor receptor 4 (HER4) can act as either a tumor suppressor or an oncogene in breast cancer.

Objectives: We proposed that rs1595065 3?UTR variant of HER4 with a different target binding site of miRNAs may have a correlation with risk of BC phenotypes. In the current study, we aimed to evaluate the association between HER4 rs1595065 3'UTR variant and BC pathological features among the Isfahanian population. Moreover, an in-silico prediction was performed to estimate possible function of the rs1595065.

Methods: Overall, 156 patients and controls were genotyped using RFLP-PCR. Armitage test for trend was utilized to investigate the association between rs1595065 and susceptibility to BC. The possible change in the interaction between rs1595065 and microRNAs was studied bioinformatically.

Results: Bioinformatics analysis using online tools suggest rs1595065 as a polymorphism in the seed region of four miRNAs binding sites including miR-199a-3p, miR-199b-3p, miR-1244 and miR-3129, and C allele can reduce miRNA-mRNA binding occurrence that may increase HER4 expression. Armitages trend test showed that C allele of rs1595065 was significantly associated with HER2 positivity among patients (C allele vs. T allele, OR = 3.111, P = 0.046).

Conclusions: rs1595065 could be recommended as a risk factor in regulating HER4 expression and affecting HER2 positivity incidence among BC patients.


Breast Cancer Single Nucleotide Polymorphism ErbB4 miRNA

© 2016, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
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