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Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in chronic myeloid leukemia: an Egyptian study

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Abstract

Methylenetetrahydrofolate reductase (MTHFR) gene plays a pivotal role in folate metabolism. Several genetic variations in MTHFR gene as MTHFR-C677T and MTHFR-A1298C result in decreased MTHFR activity, which could influence efficient DNA methylation and explain susceptibility to different cancers. The etiology of chronic myeloid leukemia (CML) is obscure and little is known about individual’s susceptibility to CML. In order to assess the influence of these genetic polymorphisms on the susceptibility to CML and its effect on the course of the disease among Egyptians, we performed an age–gender–ethnic matched case–control study. The study included 97 CML patients and 130 healthy controls. Genotyping of MTHFR-C677T and -A1298C was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) technique. The results showed no statistical difference in the distribution of MTHFR-C677T and -A1298C polymorphic genotypes between CML patients and controls. The frequency of MTHFR 677-TT homozygous variant was significantly higher in patients with accelerated/blastic transformation phase when compared to those in the chronic phase of the disease. In conclusion, our study revealed that MTHFR-C677T and -A1298C polymorphisms could not be considered as genetic risk factors for CML in Egyptians. However, MTHFR 677-TT homozygous variant might be considered as a molecular predictor for disease progression.

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References

  1. Albano F, Zagaria A, Coccaro N, Impera L, Minervini CF, Minervini A, Rossi AR, Tota G, Casieri P. Gene expression profiling of chronic myeloid leukemia with variant t(9;22) reveals a different signature from cases with classic translocation. Mol Cancer. 2013;12:36.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Lordelo GS, Miranda-Vilela AL, Akimoto AK, Alves PC, Hiragi CO, Nonino A, Daldegan MB, Klautau-Guimarães MN, Grisolia CK. Association between methylene tetrahydrofolate reductase and glutathione S-transferase M1 gene polymorphisms and chronic myeloid leukemia in a Brazilian population. Genet Mol Res. 2012;11(2):1013–26.

    Article  CAS  PubMed  Google Scholar 

  3. Nowicki MO, Falinski R, Koptyra M, Slupianek A, et al. BCR/ABL oncogenic kinase promotes unfaithful repair of the reactive oxygen species-dependent DNA double-strand breaks. Blood. 2004;104:3746–53.

    Article  CAS  PubMed  Google Scholar 

  4. Kim DH, Xu W, Ma C, Liu X, et al. Genetic variants in the candidate genes of the apoptosis pathway and susceptibility to chronic myeloid leukemia. Blood. 2009;113:2517–25.

    Article  CAS  PubMed  Google Scholar 

  5. Zagaria A, Anelli L, Albano F, Storlazzi CT, Liso A, Roberti MG, Buquicchio C, Liso V, Rocchi M, Specchia G. A fluorescence in situ hybridization study of complex t(9;22) in two chronic myelocytic leukemia cases with a masked Philadelphia chromosome. Cancer Genet Cytogenet. 2004;150:81–5.

    Article  CAS  PubMed  Google Scholar 

  6. Gouda HM, Abdel Mohsen MM. Frequency of expression of RHAMM/CD168 in Egyptian patients with CML. J Egypt Natl Canc Inst. 2009;21(2):93–9.

    PubMed  Google Scholar 

  7. Robien K, Ulrich CM, Bigler J, Yasui Y, Gooley T, Bruemmer B. Methylenetetrahydrofolate reductase genotype affects risk of relapse after hematopoietic cell transplantation for chronic myelogenous leukemia. Clin Cancer Res. 2004;10(22):7592–8.

    Article  CAS  PubMed  Google Scholar 

  8. Vahid P, Farnaz R, Zaker F, Farzaneh A, Parisa R. Methylenetetrahydrofolate Reductase gene polymorphisms and risk of myeloid leukemia. Lab Med. 2010;41:490–4.

    Article  Google Scholar 

  9. Bowen DT, Frew ME, Rollinson S, Roddam PL, et al. CYP1A1*2B (Val) allele is overrepresented in a subgroup of acute myeloid leukemia patients with poor-risk karyotype associated with NRAS mutation, but not associated with FLT3 internal tandem duplication. Blood. 2003;101:2770–4.

    Article  CAS  PubMed  Google Scholar 

  10. Miranda-Vilela AL. Role of polymorphisms in factor V (FV Leiden), prothrombin, plasminogen activator inhibitor type-1 (PAI-1), methylenetetrahydrofolate reductase (MTHFR) and Cystathionine ß-synthase (CBS) genes as risk factors for thrombophilias. Mini Rev Med Chem. 2012;12:997–1006.

    Article  CAS  PubMed  Google Scholar 

  11. Wiemels JL, Smith RN, Taylor GM, Eden OB, Alexander FE, Greaves MF. United Kingdom childhood cancer study investigators. Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci U S A. 2001;98(7):4004–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111–3.

    Article  CAS  PubMed  Google Scholar 

  13. Murphy TM, Perry AS, Lawler M. The emergence of DNA methylation as a key modulator of aberrant cell death in prostate cancer. Endocr Relat Cancer. 2008;15:11–25.

    Article  CAS  PubMed  Google Scholar 

  14. Sinthuwiwat T, Poowasanpetch P, Wongngamrungroj A, Soonklang K, Promso S, et al. Association of MTHFR polymorphisms and chromosomal abnormalities in leukemia. Dis Markers. 2012;32:115–21.

    Article  CAS  PubMed  Google Scholar 

  15. Zhu J, Wu L, Kohlmeier M, Ye F, Cai W. Association between MTHFR C677T, MTHFR A1298C and MS A2756G polymorphisms and risk of cervical intraepithelial neoplasia II/III and cervical cancer: a meta-analysis. Mol Med Rep. 2013;8(3):919–27.

    CAS  PubMed  Google Scholar 

  16. Robien K, Bigler J, Yasui Y, Potter JD, Martin P, Storb R, Ulrich CM. Methylenetetrahydrofolate reductase and thymidylate synthase genotypes and risk of acute graft-versus-host disease following hematopoietic cell transplantation for chronic myelogenous leukemia. Biol Blood Marrow Transplant. 2006;12(9):973–80.

    Article  CAS  PubMed  Google Scholar 

  17. van der Put NM, Gabreëls F, Stevens EM, Smeitink JA, Trijbels FJ, et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet. 1998;62:1044–51.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Suarez-Kurtz G. Pharmacogenomics in admixed populations: the Brazilian pharmacogenetics/pharmacogenomics network–REFARGEN. Pharmacogenomics J. 2004;4:347–8.

    Article  CAS  PubMed  Google Scholar 

  19. Barreiro LB, Laval G, Quach H, Patin E, et al. Natural selection has driven population differentiation in modern humans. Nat Genet. 2008;40:340–5.

    Article  CAS  PubMed  Google Scholar 

  20. Jakovljevic K, Malisic E, Cavic M, Radulovic S, Jankovic R. Association between methylenetetrahydrofolate reductase polymorphism C677T and risk of chronic myeloid leukemia in Serbian population. Leuk Lymphoma. 2012;53(7):1327–30. doi:0.3109/10428194.2011.645210.

    Article  CAS  PubMed  Google Scholar 

  21. Weisberg IS, Jacques PF, Selhub J, et al. The 1298A–>C poly-morphism in methylenetetrahydrofolate reductase (MTHFR): in vitro expression and association with homocysteine. Atherosclerosis. 2001;156:409–15.

    Article  CAS  PubMed  Google Scholar 

  22. Li D, Tian T, Guo C, Ren J, Yan L, Liu H, Xu Z. No association of the MTHFR gene A1298C polymorphism with the risk of prostate cancer: a meta-analysis. Exp Ther Med. 2012;3(3):493–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Ismail SI, Ababneh NA, Awidi A. Methylenetetrahydrofolate Reductase (MTHFR) genotype association with the risk of chronic myelogenous leukemia. Jorden Med J. 2009;43(1):8–14.

    Google Scholar 

  24. Hussain SR, Naqvi H, Raza ST, Ahmed F, Babu SG, Kumar A, Zaidi ZH, Mahdi F. Methylenetetrahydrofolate reductase C677T genetic polymorphisms and risk of leukaemia among the North Indian population. Cancer Epidemiol. 2012;36(4):e227–31. doi:10.1016/j.canep.2012.02.008.

    Article  CAS  PubMed  Google Scholar 

  25. Moon HW, Kim TY, Oh BR, Min HC, Cho HI, Bang SM, Lee JH, Yoon SS, Lee DS. MTHFR 677CC/1298CC genotypes are highly associated with chronic myelogenous leukemia: a case-control study in Korea. Leuk Res. 2007;31(9):1213–7.

    Article  CAS  PubMed  Google Scholar 

  26. Hur M, Park JY, Cho HC, Lee KM, Shin HY, Cho HI. Methylenetetrahydrofolate reductase A1298C genotypes are associated with the risks of acute lymphoblastic leukaemia and chronic myelogenous leukaemia in the Korean population. Clin Lab Haematol. 2006;28(3):154–9.

    Article  CAS  PubMed  Google Scholar 

  27. Grillo LB, Acácio GL, Barini R, Pinto W Jr, Bertuzzo CS. Mutations in the methylene-tetrahydrofolate reductase gene and down syndrome. Cad Saude Publica. 2002;6:1795–7.

    Article  Google Scholar 

  28. Johansson B, Fioretos T, Mitelman F. Cytogenetic and molecular genetic evolution of chronic myeloid leukemia. Acta Haematol. 2002;107:76–94.

    Article  CAS  PubMed  Google Scholar 

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt

    Mervat Mamdooh Khorshied & Reham E. Abu Khalil

  2. 23 Gezeret El Arab Street, El Mohandeseen, Giza, 12411, Egypt

    Mervat Mamdooh Khorshied

  3. Faculty of Medicine, Cairo University, Cairo, Egypt

    Iman Abdel Mohsen Shaheen

  4. Beni Sweif University, Beni Suef, Egypt

    Rania Elsayed Sheir

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  1. Mervat Mamdooh Khorshied
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  2. Iman Abdel Mohsen Shaheen
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  3. Reham E. Abu Khalil
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  4. Rania Elsayed Sheir
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Correspondence to Mervat Mamdooh Khorshied.

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Khorshied, M.M., Shaheen, I.A.M., Abu Khalil, R.E. et al. Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in chronic myeloid leukemia: an Egyptian study. Med Oncol 31, 794 (2014). https://doi.org/10.1007/s12032-013-0794-2

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  • DOI: https://doi.org/10.1007/s12032-013-0794-2

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