Correlations of EZH2 and SMYD3 gene polymorphisms with breast cancer susceptibility and prognosis.

Shao-Jun Ma,Yan-Mei Liu,Ming-Wei Chen,Yue-Lang Zhang,Wei Cao

doi:10.1042/bsr20170656

Abstract

The aim of the present study was to investigate the correlation of enhancer of Zeste homolog 2 (EZH2) and SET and MYND domain containing 3 (SMYD3) gene polymorphisms with breast cancer susceptibility and prognosis. A total of 712 patients with breast cancer and 783 healthy individuals were selected. Normal breast epithelial cells MCF-10A and breast cancer cells MCF-7, MDA-MB-231, T47D, and Bcap-37 were cultured. Polymerase chain reaction (PCR)-restriction fragment length polymorphism method was applied for genotyping. Reverse-transcription quantitative PCR (RT-qPCR) and Western blotting were used to examine EZH2 and SMYD3 expression in breast cancer tissues and cells. The risk factors and prognostic factors for breast cancer were estimated. The C allele of EZH2 rs12670401 (odds ratio (OR) =1.255, 95% confidence interval (95% CI): 1.085–1.452), T allele of EZH2 rs6464926 (OR =1.240, 95% CI: 1.071–1.435), and three alleles of SMYD3 variable number of tandem repeats (VNTRs) (OR =1.305, 95% CI: 1.097–1.552) could increase susceptibility to breast cancer. Combined genotypes of EZH2 rs12670401 (TC + CC) and EZH2 rs6464926 (CT + TT) were associated with breast cancer susceptibility. Breast cancer tissues had higher EZH2 and SMYD3 expression. EZH2 rs12670401, EZH2 rs6464926, age of menarche, and menopausal status were associated with breast cancer susceptibility. Patients with TT genotype of EZH2 rs12670401 or with CC genotype of EZH2 rs6464926 had higher overall survival (OS). EZH2 rs12670401, EZH2 rs6464926, and clinical staging were independent prognostic factors for breast cancer. SMYD3 VNTR polymorphism exhibited no association with susceptibility and prognosis. EZH2 rs12670401 and rs6464926 polymorphisms, EZH2 and SMYD3 expression, clinical staging, lymph node metastasis, human epidermal growth factor receptor-2 (HER2) status, and metastasis may be correlated with breast cancer susceptibility and prognosis.

Highlights

Breast cancer, the most common malignant tumor in the world and second common malignant tumor in China, ranks sixth as the cause of female tumor deaths [1]
Patients with age over 40 years accounted for 83.01%; 75.28% patients were positive in estrogen receptor (ER+) and 76.41% were positive in progesterone receptor (PR+); 91.85% patients were in clinical stage I or II, and 8.15% (58 cases) were in stage III or IV; 377 cases
The present study aims to explore the correlations of enhancer of Zeste homolog 2 (EZH2) and SET and MYND domain containing 3 (SMYD3) gene polymorphisms with breast cancer susceptibility and prognosis

Summary

Introduction

The most common malignant tumor in the world and second common malignant tumor in China, ranks sixth as the cause of female tumor deaths [1]. Surgical therapy is currently the main treatment for breast cancer, including hormonal therapy, chemotherapy, radiotherapy, and molecular targetted therapy [3]. Many molecular targets have been identified in breast cancer: trastuzumab and lapatinib target the human epidermal growth factor receptor-2 (HER2) and are approved drugs for the treatment of metastatic breast cancer [4]. The expression abnormality c 2018 The Author(s).

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