DNA Repair Genes Polymorphisms: Impact on Acute Myeloid Leukemia Patients Outcome

Aref, Salah; El Menshawy, Nadia; Abou Zeid, Tarek; Gouda, Enas; Abdel Aziz, Nora

doi:10.31557/APJCP.2022.23.10.3577

DNA Repair Genes Polymorphisms: Impact on Acute Myeloid Leukemia Patients Outcome

Document Type : Research Articles

Authors

¹ Hematology Unit, Clinical Pathology Department, Faculty of Medicine, Mansoura University, Egypt.

² Unit, Mansoura University Oncology Center (MUOC), Mansoura University, Egypt.

10.31557/APJCP.2022.23.10.3577

Abstract

Background: ATM; XRCC6 and LIG4 genes play an important role in repairing the double-strand DNA breaks and maintaining the genome stability. Single nucleotide polymorphisms (SNPs) in these genes could affect these genes expression and function. The aim of this study was to address the effect of SNP of the DNA repairing genes on corresponding gene expression as well as AML patient’s outcome. Subjects and Methods: This is cross sectional study included 95 newly diagnosed AML patients. For all subjects included in our study SNPs and expression of ATM (rs189037G>A), XRCC6 (rs2267437C>G) and LIG4 (rs1805388C>T) genes were evaluated by RFLP and real time PCR. Results:The following SNPs in ATM (AA); XRCC6 (GG); and LIG4 (TT) are associated with down regulation of the corresponding genes (P<0.001). The lower expression of ATM and LIG4 genes are associated with shorter OS and DFS. Cox regression multivariate analysis revealed that lower expression of ATM HR : 2.02 (CI: 1.12-3.64; p=0.020. Conclusion: The following SNPs of ATM (AA); XRCC6 (GG); and LIG4 (TT) are associated with down regulation of corresponding genes expression. ATM and XRCC6 lower expression are predictors of OS while ATM is predictor of DFS and could be used for optimizing the AML therapy.

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