The impact of the ERCC2 Lys751Gln polymorphism on the risk of acute myeloid leukemia in an Iraqi patients
Keywords:Leukemia, Myeloid, Acute, ERCC2, Polymorphism, Genetic, DNA Repair
Objectives: AML is the only type of acute leukemia diagnosed in adults and is less common in children. It has the lowest survival rate. This study aimed to investigate the epidemiological risk factors for AML expansion comprise environmental factors, for instance, smoking , and therapy-related factors.
Methods :The study was conducted on 70 acute myeloid leukemia patients—37 females and 33 males and on 30 healthy people—12 females and 18 males—as a control group. DNA was extracted from the study groups' whole blood samples using the gSYNCTM DNA Extraction Kit. The T751G polymorphism of the ERCC2 gene was determined by the PCR-RFLP technique.
Results: In genetic analysis, it was shown that the carriers of allele Lys and genotype Lys/Lys have a lower risk of developing AML, while allele carriers Gln have an increased risk. The results showed the ERCC2 gene, Lys 751 Gln (T/G) heterozygous TG genotypes, and the G allele were significantly higher (P<0.05) in AML patients compared to the control group. In the sequencing of the region we studied, it was found that there is a site of diversity that is located between the CTTCAG and CTGCAG, where a change in nucleotides (T to G) represents the restriction site of the restriction enzyme.
Conclusion : The polymorphic marker 751 Gln> Lys of the ERCC2 gene was associated with the development of AML in Iraqi patients. It was discovered that allele Lys genotype Lys/Lys carriers have a lower risk of developing AML, whereas allele Gln carriers have an increased risk.
Yamamoto, J.F. and M.T. Goodman, Patterns of leukemia incidence in the United States by subtype and demographic characteristics, 1997–2002: Cancer Causes Control, 2008. 19(4): p. 379–90. DOI: 10.1007/s10552-007-9097-2
Zeeb, H. and M. Blettner, Adult leukaemia: what is the role of currently known risk factors. Radiat Environ Biophys ,1998. 36: p.217–228.
Corces-Zimmerman, M. R. and R. Majeti, Pre-leukemic evolution of hematopoietic stem cells: the importance of early mutations in leukemogenesis. Leukemia ,2014. 28(12): p .2276-2282.
Weber, C.A., et al., ERCC2: cDNA cloning and molecular characterization of a human nucleotide excision repair gene with high homology to yeast RAD3. EMBO J , 1990. 9: p.1437–47. DOI: 10.1002/j.1460-2075.1990.tb08260.x
Schaeffer, L., et al., The ERCC2/DNA repair protein is associated with the class II BTF2/TFIIH transcription factor. EMBO J., 1994. 13: p. 2388–92. doi: 10.1002/j.1460-2075.1994.tb06522.x
Dexi, J., et al., Impact of polymorphisms in DNA repair genes XPD, hOGG1 and XRCC4 on colo-rectal cancer risk in a Chinese Han Population. Bioscience Reports ,2019. 39 : p.1-9.
Russell, D.W. , and J. Sambrook , Molecular cloning: A laboratory manual. Cold Spring Harbor: Cold Spring Harbor Laboratory, 2001.
James, M., et al., Genetic variation in XPD predicts treatment outcome and risk of acute myeloid leukemia following chemotherapy Blood, 2004. 104(13): p.3872-3877. DOI: 10.1182/blood-2004-06-2161
Ilhan, G., et al., Risk factors and primary prevention of acute leukemia. Asian Pac. J. Cancer Prev. 2006.7: p.515–517.
Ali, Ö., et al., Polymorphisms of the DNA repair gene XPD (751) and XRCC1 (399) correlates with risk of hematological malignancies in Turkish population. African Journal of Biotechnology, 2011. 10(44): p. 8860-8870.
Meenaghan, T., et al., Acute leukaemia: making sense of a complex blood cancer. Br. J. Nurs,2012. 21 (76): p.78–83. DOI: 10.12968/bjon.2012.21.2.76
Duo, L., et al., The effect of XPD/ERCC2 Lys751Gln polymorphism on acute leukemia risk: A sys-tematic review and meta-analysis Gene, 2012. 538 :p.209–216. DOI: 10.1016/j.gene.2014.01.049
Liu, D., et al., The effect of XPD/ERCC2 Lys751Gln polymorphism on acute leukemia risk: a sys-tematic review and meta-analysis. Gene, 2014. 538(2): p.209–16.
Claudia, B., et al., Influence of XPC, XPD, XPF, and XPG gene polymorphisms on the risk and the outcome of acute myeloid leukemia in a Romanian population, Tumour Biol, 2016. 37(7): p.9357-66. DOI: 10.1007/s13277-016-4815-6
Dolly, J., et al., Association of XPD (Lys751Gln) and XRCC1 (Arg280His) gene polymorphisms in myelodysplastic syndrome. Ann Hematol , 2016. 95(1): p.79-85. DOI: 10.1007/s00277-015-2528-3
Zohreh, S., et al., Genetic variants of nucleotide excision repair pathway and outcomes of induction therapy in acute myeloid leukemia. Per. Med., 2019. 16(6): p. 479–490. DOI: 10.2217/pme-2018-0077
Mehta, P.A., et al., XPD Lys751Gln polymorphism in the etiology and outcome of childhood acute myeloid leukemia: a Children's Oncology Group report, Blood. 2006. 107(1): p.39-45. DOI: 10.1182/blood-2005-06-2305
Sorour, A., et al., The genotype distribution of the XRCC1, XRCC3, and XPD DNA repair genes and their role for the development of acute myeloblastic leukemia. Genet Test Mol Biomarkers , 2013,17: p.195–201. DOI: 10.1089/gtmb.2012.0278
Kais, D.et al., Polymorphisms in XPC, XPD and XPG DNA repair genes and leukemia risk in a Tu-nisian population. Leuk Lymphoma, 2015. 56(6): p.1856-62. DOI: 10.3109/10428194.2014.974045
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