Analysis of EZH2 Genetic Variants on Triple-Negative Breast Cancer Susceptibility and Pathology

Abstract

Triple-negative breast cancer (TNBC) is the third most common female cancer in Taiwan. EZH2 plays an important role in cancer development through transcriptional repression by chromatin remodeling. However, the expression of EZH2 in breast cancer is highly correlated with tumorigenesis, and patient survival is not matched to TNBC. Furthermore, it has not been determined if specific EZH2 genetic variants are associated with breast cancer risk. In this paper, we evaluated the survival of different types of breast cancer. The results indicated that a lower expression of EZH2 led to poor survival of TNBC patients. Therefore, we aimed at studying the relationship between genetic polymorphisms of EZH2 and susceptibility to TNBC in Taiwan. Four single-nucleotide polymorphisms (SNPs) of EZH2 (rs6950683, rs2302427, rs3757441, and rs41277434) were analyzed by real-time PCR genotyping in 176 patients with TNBC and 1000 cancer-free controls. The results showed that TNBC patients under 60 years old who carried a TC or CC genotype at EZH2 rs6950683 and re3757441 had a tumor size of 20 mm or smaller (T1). Thus, this study is the first to examine the age and mutant genes associated with EZH2 SNPs in TNBC progression and development in Taiwan.

Exploring the Genetic Predisposition to Epigenetic Changes in Alzheimer’s Disease

“…It is known that along with the impact of environmental factors, genetic pre-disposition plays an important role in the epigenetic changes associated with various pathologies [39,46]. Numerous examples of different pathologies related to genetic variation (SNPs) underlying the abnormalities in the expression or function of the genes coding for epigenetic factors, including histone acetylases [99,100], deacetylases [101][102][103], histone methyltransferases [102,104], and components of chromatin remodeler complexes [105,106], have been thus far accumulated. However, most of these results have been obtained when studying different types of cancer.…”

“…However, most of these results have been obtained when studying different types of cancer. For example, two SNPs (rs6950683 and re3757441) of EZH2 coding for the histone methyltransferase that causes the trimethylation of H1K26 and, consequently, suppresses the cancer preventive genes were shown to be associated with a tumor size in triple-negative breast cancer [102]. Further, the association-based study of SNP rs201135441C>T shows that the T allele of rs201135441 significantly increases the risk of breast cancer susceptibility and reduces the overall survival rate [107].…”

Exploring the Association Between PRC2 Genes Variants and Lung Cancer Risk in Chinese Han Population

“…17 Given the importance of PRC2 in the development and progression of many tumors, genetic variants within PRC2 have been implicated in susceptibility to different cancers, including prostate 22 and triple-negative breast cancer. 23 A previous study reported that the C/C genotype of rs6950683 and the C/C genotype of rs3757441 in EZH2 reduced susceptibility to oral squamous cell carcinoma. 24 Additionally, Hyuna Sung et al 25 identified a protective effect of the T variant at the rs10898459 site in EED against esophageal squamous cell carcinoma.…”

Tumor-Intrinsic Enhancer of Zeste Homolog 2 Controls Immune Cell Infiltration, Tumor Growth, and Lung Metastasis in a Triple-Negative Breast Cancer Model

“…Genetic and epigenetic alterations in TNBC are some of the main obstacles for successful responses to therapy [7]. Among the TNBC markers identified as potential therapeutic targets, the methyltransferase enhancer of zeste homolog 2 (EZH2) holds significant promise, as its overexpression is associated with poor prognosis and short disease-free survival in patients [8][9][10][11]. This may occur in part through the increased stability of EZH2 due to upstream regulatory pathways leading to its post-translational modification in aggressive TNBCs [12].…”

“…In this study, we probed the role of EZH2 in primary and metastatic TNBCs [18] using a 4T1 murine TNBC model. EZH2 was previously shown to be significantly upregulated in 4T1 compared to normal mouse breast epithelial cells [10]. To this end, we used CRISPR technology to drive EZH2 gene knockout (KO) and overexpression (OE) in stable cell lines derived from parent wild-type (WT) 4T1 cells, resulting in EZH2 protein KO and OE, respectively.…”