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

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.