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

Abstract

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. Armitage’s 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.