Tumor Biology

, Volume 36, Issue 12, pp 9849–9855 | Cite as

The possible role of EZH2 and DNMT1 polymorphisms in sporadic triple-negative breast carcinoma in southern Chinese females

  • Ran Tao
  • Zekun Chen
  • Pingping Wu
  • Cuicui Liu
  • You Peng
  • Weiwei Zhao
  • Chaohui Hu
  • Jing Feng
Research Article


Triple-negative breast cancer (TNBC) has a more invasive and metastatic potential than the other types of breast cancer and hence is associated with poor prognosis. Zeste homolog 2 (EZH2) and DNA methyltransferase 1 (DNMT1) could lead to tumorigenesis by separately methylating histone H3K27 and CpG islands in tumor suppressor genes. In order to investigate the association between oncogenesis and the distribution of single nucleotide polymorphisms (SNPs) of EZH2, DNMT1, a case–control study on SNPs in TNBC cases from south China was conducted. A total of 13 SNPs were genotyped from 234 cases of TNBC tissues, and 300 normal blood samples from age-matched control group were analyzed using Snapshot technology. The expressions of EZH2 and DNMT1 were examined in the 234 cases of TNBC tissues by immunohistochemistry (IHC). The T allele of rs2288349 and the C allele of rs16999593 increase the risk of TNBC, with relative risk coefficients of 1.76 and 1.69, respectively (p < 0.001). The TC genotypes of rs2288349 and rs16999593 were higher in TNBC compared with the control group; the cancer risk increased to 5.27 and 4.13, respectively (p < 0.001). There were no significant differences between the frequencies of the other 10 SNPs and the risk of TNBC (p > 0.05). Five common haplotypes (>8 % frequency) were identified with a cumulative frequency of 96 % in the controls, while the haplotypes of AAGTAG, GGGTGA, and GACCAG were significantly increased in the control group compared to that in patients (p < 0.05). The G allele of rs10274701 significantly increased the EZH2 expression level in TNBC (p = 0.01). This is the first study to demonstrate a significant association between TNBC risk and the polymorphisms of EZH2 and DNMT1, and our researches indicate that the SNPs of EZH2 and DNMT1 are risk predictors for TNBC.


Triple-negative breast cancer Single nucleotide polymorphism EZH2 DNMT1 



This work was supported by the Nature Science Foundation of Shanghai (12ZR1426300) and the Shanghai Health System outstanding academic leader training program (XBR2013114).

Conflicts of interest


Supplementary material

13277_2015_3754_MOESM1_ESM.docx (329 kb)
ESM 1 (DOCX 328 kb)


  1. 1.
    American Cancer Society. Cancer facts and figures 2014. Atlanta: American Cancer Society; 2014.Google Scholar
  2. 2.
    Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.CrossRefPubMedGoogle Scholar
  3. 3.
    Bauer KR, Brown M, Cress RD, et al. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California Cancer Registry. J Cancer. 2007;109(9):1721–8.CrossRefGoogle Scholar
  4. 4.
    Antoni RJ. Novel genetic mapping tools in plants: SNPs and LD-based approaches. Plant Sci. 2002;162:329–33.CrossRefGoogle Scholar
  5. 5.
    Van de Rijn M, Perou CM, Tibshirani R, et al. Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol. 2002;161(6):1991–6.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Jeltsch A. Beyond Watson and Crick: DNA methylation and molecular enzymology of DNA methyltransferases. Chem Biochem. 2002;3(4):274–93.Google Scholar
  7. 7.
    Montgomery ND, Yee D, Chen A, et al. The murine polycomb group protein Eed is required for global histone H3 lysine-27 methylation. Curr Biol. 2005;15(10):942–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Gabriel SB, Schaffner SF, Nguyen H, et al. The structure of haplotype blocks in the human genome. Science. 2002;296(5576):2225–9.CrossRefPubMedGoogle Scholar
  9. 9.
    De Bakker PI, Yelensky R, Pe’Er I, et al. Efficiency and power in genetic association studies. Nat Genet. 2005;37(11):1217–23.CrossRefPubMedGoogle Scholar
  10. 10.
    Shi Y, He L. SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res. 2005;15(2):97–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Wjst M. Target SNP, selection in complex disease association studies. BMC Bioinf. 2004;5:92.CrossRefGoogle Scholar
  12. 12.
    Mccarty KJ, Szabo E, Flowers JL, et al. Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors. Cancer Res. 1986;46:4244s–8.PubMedGoogle Scholar
  13. 13.
    Ye C, Beeghly-Fadiel A, Lu W, et al. Two-stage case–control study of DNMT-1 and DNMT-3B gene variants and breast cancer risk. Breast Cancer Res Treat. 2010;121(3):765–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Stevens KN, Vachon CM, Lee AM, et al. Common breast cancer susceptibility loci are associated with triple-negative breast cancer. Cancer Res. 2011;71(19):6240–9.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Stevens KN, Fredericksen Z, Vachon CM, et al. 19p13.1 is a triple-negative-specific breast cancer susceptibility locus. Cancer Res. 2012;72(7):1975–803.CrossRefGoogle Scholar
  16. 16.
    Svedruzic ZM. Dnmt1 structure and function. Prog Mol Biol Transl Sci. 2011;101:221–54.CrossRefPubMedGoogle Scholar
  17. 17.
    Jiang J, Jia Z, Cao D, et al. Polymorphisms of the DNA methyltransferase 1 associated with reduced risks of Helicobacter pylori infection and increased risks of gastric atrophy. PLoS One. 2012;7(9):e46058.Google Scholar
  18. 18.
    Hoehe MR. Haplotypes and the systematic analysis of genetic variation in genes and genomes. Pharmacogenomics. 2003;4(5):547–70.CrossRefPubMedGoogle Scholar
  19. 19.
    Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002;3:415–28.CrossRefPubMedGoogle Scholar
  20. 20.
    Crea F, Fornaro L, Paolicchi E, et al. An EZH2 polymorphism is associated with clinical outcome in metastatic colorectal cancer patients. Ann Oncol. 2012;23(5):1207–13.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Ran Tao
    • 1
    • 3
  • Zekun Chen
    • 2
  • Pingping Wu
    • 1
  • Cuicui Liu
    • 1
  • You Peng
    • 1
  • Weiwei Zhao
    • 1
  • Chaohui Hu
    • 3
  • Jing Feng
    • 1
  1. 1.Laboratory MedicineSouthern Medical University Affiliated Fengxian HospitalShanghaiChina
  2. 2.Third Clinical CollegeSouthern Medical UniversityGuangzhouChina
  3. 3.Guangzhou Kingmed Centre for Clinical LaboratoryGuangzhouChina

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