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. 2018 Feb 2;38(1):BSR20170656.
doi: 10.1042/BSR20170656. Print 2018 Feb 28.

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

Shao-Jun Ma  1 , Yan-Mei Liu  2 , Yue-Lang Zhang  3 , Ming-Wei Chen  4 , Wei Cao  5
Affiliations

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

Shao-Jun Ma et al. Biosci Rep. .

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.

Keywords: Breast cancer; EZH2; Polymorphism; Prognosis; SMYD3; Susceptibility.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Electrophoresis maps of EZH2 rs12670401, EZH2 rs6464926, and SMYD3VNTR gene polymorphisms
(A) Electrophoresis maps of EZH2 rs12670401 gene polymorphisms. M, DNA marker; TC, TC heterozygotes digestion products, 189, 159, 30 bp; CC, CC homozygotes digestion products, 159 and 30 bp; TT, TT homozygotes digestion product, 189 bp. (B) Electrophoresis map of EZH2 rs6464926 gene polymorphisms. M, DNA marker; CC, CC homozygotes digestion products, 151 bp; TT, TT homozygotes digestion products, 124 and 27 bp; CT, CT heterozygotes digestion products, 124, 151, and 27 bp. (C) Electrophoresis map of SMYD3 VNTR gene polymorphisms. M, DNA marker; 3/3, 3/3 homozygote digestion products, 175 and 23 bp; 2/3, 2/3 heterozygotes digestion products, 198, 175, and 23 bp; 2/2, 2/2 homozygotes digestion products, 198 bp.
Figure 2
Figure 2. Expression of EZH2 and SMYD3 in cancer tissues and adjacent tissues
(A) mRNA expression of EZH2 and SMYD3 in cancer tissues and adjacent tissues. (B) Western blotting. (C) Protein expression of EZH2 and SMYD3 in cancer tissues and adjacent tissues.
Figure 3
Figure 3. mRNA and protein expression of EZH2 and SMYD3 in breast cancer cells
(A) mRNA expression of EZH2 and SMYD3 in breast cancer cells. (B) Immunoblotting map. (C) Protein expression of EZH2 and SMYD3 in breast cancer cells; *P<0.05, compared with MCF-10A cells.
Figure 4
Figure 4. Correlation of EZH2 rs12670401, EZH2 rs6464926, and SMYD3VNTR gene polymorphisms with the OS of patients with breast cancer
(A) OS curve for patients with breast cancer. (B) Survival curve for patients with EZH2 rs12670401. (C) Survival curve for patients with EZH2 rs6464926. (D) Survival curve for patients with SMYD3 VNTR genotypes. (E) Survival curve for mRNA expression of EZH2. (F) Survival curve for mRNA expression of SMYD3.
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