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EZH2 Expression and Survival for ER+/tamoxifen Treated Breast Cancer Patients with rs2302427 C>G: A Novel Prognostic
Nisha Gautam1, Satbir Kaur1, Surender Kashyap2
1Laboratory of Molecular Genetics, Department of Human Genetics, Punjabi University, Patiala, India.
Background And Objectives:
Overexpression of the EZH2 gene silences several genes involved in DNA repair, cell-cell adhesion, and tumor suppressor genes, resulting in the development of several types of cancers. In the present study, a genetic polymorphism analysis was performed by selecting three SNPs (rs.2302427C>G, rs.3757441C>T, and rs.6950683T>C) of the EZH2 gene based on our previous in silico studies.
Methods:
A total of 250 breast cancer patients and 250 healthy individuals were recruited for the study. Patients with pre-operative breast cancer with different clinical-pathological variables and age-matched healthy women were recruited for the EZH2 gene expression analysis.
Results:
The genetic polymorphism analysis revealed two SNPs (rs.2302427C>G and rs.6950683T>C) of the three studied SNPs of the EZH2 gene have a protective role in all three genetic models. The haplotype analysis predicted that two haplotypes ACGT and ACGC were significantly associated with a lower risk of breast cancer.
Interpretation And Conclusions:
Three significant findings of the SNP rs.2302427C>G (Asp193His) i.e., protective role against breast cancer, survival advantage in ER+/tamoxifen treated breast cancer patients, and decreased expression due to the presence of mutant GG genotype, suggests considering it as an important prognostic biomarker for a good survival outcome of breast cancer patients treated with ER+/tamoxifen. Compared with other studies, the other SNP rs.3757441T>C was observed to have a protective effect in breast cancer biology but plays an antagonistic role in colorectal cancer (CRC) biology. To our knowledge, this is the first detailed study on computationally validated EZH2 SNPs in breast cancer.
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