https://doi.org/10.4081/itjm.2023.1644
Association of methionine synthase reductase (MTRR A66G) polymorphism with susceptibility to acute lymphoblastic leukemia
Published: 13 September 2023
Abstract Views: 880
PDF: 226
HTML: 27
HTML: 27
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Background and Objectives. The enzyme methionine synthase reductase is involved in cellular methylation reactions, DNA synthesis, and epigenetic processes. It is encoded by the MTRR gene, which garnered a lot of attention in current medical genetics research. This study was conducted to study the association between MTRR (A66G) polymorphism and the risk of developing acute lymphoblastic leukemia among Sudanese patients. Materials and Methods. This is a case-control study in which 150 patients with acute lymphoblastic leukemia (ALL) and 150 healthy participants as a control group were enrolled. DNA was extracted and analyzed for the MTRR (A66G) polymorphism using the real-time polymerase chain reaction. Results. Based on flow cytometry results, B-ALL was more common (79%) than T-ALL (21%). The comparison of hematological parameters in acute lymphoblastic leukemia subtypes showed a statistically significant high mean total white blood count (P=0.000) and mean blast percentage (P=0.050) in patients with T-ALL. The molecular analysis showed that the incidence of the MTRR homozygous genotypes AA and GG were higher in the patients (44% and 9.3%, respectively) compared to the control group (40% and 6.7%, respectively). In comparison, the heterozygous genotype AG was lower in the patients (46.7%) than in the control group (53.3%). However, the association between the polymorphism and acute lymphoblastic leukemia risk was not statistically significant (OR: 1.179, 95% CI 0.7459-1.865, P=0.445). Conclusions. This study concluded that MTRR A66G polymorphism was not associated with the risk of acute lymphoblastic leukemia among the Sudanese population.
Pui C-H, Evans WE. Treatment of acute lymphoblastic leukemia. New Eng J Med 2006;354:166-78.
DOI: https://doi.org/10.1056/NEJMra052603
Coccaro N, Anelli L, Zagaria A, et al. Next-Generation Sequencing in Acute Lymphoblastic Leukemia. Int J Mol Sci 2019;20:2929.
DOI: https://doi.org/10.3390/ijms20122929
Lautner-Csorba O, Gézsi A, Erdélyi DJ, et al. Roles of Genetic Polymorphisms in the Folate Pathway in Childhood Acute Lymphoblastic Leukemia Evaluated by Bayesian Relevance and Effect Size Analysis. PLoS ONE 2013;8:e69843.
DOI: https://doi.org/10.1371/journal.pone.0069843
Hiraoka M, Kagawa Y. Genetic polymorphisms and folate status. Congenit Anom 2017;57:142-9.
DOI: https://doi.org/10.1111/cga.12232
Schwahn B, Rozen R. Polymorphisms in the Methylenetetrahydrofolate Reductase Gene. Ame J Pharmacogenomics 2001;1;189-201.
DOI: https://doi.org/10.2165/00129785-200101030-00004
Wiseman MJ. Nutrition and cancer: prevention and survival. Brit J Nutr 2019;122:481-7.
DOI: https://doi.org/10.1017/S0007114518002222
Kawakita D, Amy Lee YC, Gren LH, et al. The impact of folate intake on the risk of head and neck cancer in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) cohort. Brit J Cancer 2018;118:299-306.
DOI: https://doi.org/10.1038/bjc.2017.383
Minatel BC, Page AP, Anderson C, et al., Environmental arsenic exposure: from genetic susceptibility to pathogenesis. Environ Int 2018;112:183-97.
DOI: https://doi.org/10.1016/j.envint.2017.12.017
Lewandowska AM, Rudzki M, Rudzki S, et al. Environmental risk factors for cancer-review paper. Ann Agric Environ Med 2018;26:1-7.
DOI: https://doi.org/10.26444/aaem/94299
Bhatia S. Genetic variation as a modifier of association between therapeutic exposure and subsequent malignant neoplasms in cancer survivors. Cancer 2015;121:648-63.
DOI: https://doi.org/10.1002/cncr.29096
Peres NP, Galbiatti-Dias ALS, Castanhole-Nunes MMU, et al. Polymorphisms of folate metabolism genes in patients with cirrhosis and hepatocellular carcinoma. World J Hepatol 2016;8:1234.
DOI: https://doi.org/10.4254/wjh.v8.i29.1234
de Lima ELS, da Silva VC, da Silva HAD, et al. MTR polymorphic variant A2756G and retinoblastoma risk in Brazilian children. Pediatr Blood Cancer 2010;54:904-8.
DOI: https://doi.org/10.1002/pbc.22472
Wu X, Zou T, Cao N, et al. Plasma homocysteine levels and genetic polymorphisms in folate metablism are associated with breast cancer risk in chinese women. Hered Cancer Clin Pract 2014;12:1-11.
DOI: https://doi.org/10.1186/1897-4287-12-2
Asante I, Chiu D, Pei H, et al. Alterations in folate-dependent one-carbon metabolism as colon cell transition from normal to cancerous. J Nutr Biochem 2019;69:1-9.
DOI: https://doi.org/10.1016/j.jnutbio.2019.02.008
Fang D-H, Ji Q, Fan C-H, et al. Methionine synthase reductase A66G polymorphism and leukemia risk: evidence from published studies. Leuk Lymphoma 2014;55: 1910-4.
DOI: https://doi.org/10.3109/10428194.2013.867492
Pabalan N, Singian E, Tabangay L, et al. Associations of the A66G Methionine Synthase Reductase Polymorphism
in Colorectal Cancer: A Systematic Review and Meta-Analysis: Supplementary Issue: Biomarkers for Colon Cancer. Biomark Cancer 2015;7:21-8.
DOI: https://doi.org/10.4137/BIC.S39882
Gaughan DJ, Kluijtmans LA, Barbaux S, et al. The methionine synthase reductase (MTRR) A66G polymorphism is a novel genetic determinant of plasma homocysteine concentrations. Atherosclerosis 2001;157: 451-6.
DOI: https://doi.org/10.1016/S0021-9150(00)00739-5
Basir A. Methionine synthase reductase-A66G and-C524T single nucleotide polymorphisms and prostate cancer: a case-control trial. Asian Pacific Journal of Cancer Prevention: APJCP 2019;20:1445.
DOI: https://doi.org/10.31557/APJCP.2019.20.5.1445
Yang L, Liu L, Wang J, et al. Polymorphisms in folate-related genes: impact on risk of adult acute lymphoblastic leukemia rather than pediatric in Han Chinese. Leuk Lymphoma 2011;52:1770-6.
DOI: https://doi.org/10.3109/10428194.2011.578186
Kim HN, Kim YK, Lee IK, et al. Association between polymorphisms of folate-metabolizing enzymes and hematological malignancies. Leuk Res 2009;33:82-7.
DOI: https://doi.org/10.1016/j.leukres.2008.07.026
Aksoy-Sagirli P, Erdenay A, Kaytan-Saglam E, et al. Association of three single nucleotide polymorphisms in MTR and MTRR genes with lung cancer in a Turkish population. Genet Test Mol Biomarkers 2017;21:428-32.
DOI: https://doi.org/10.1089/gtmb.2017.0062
Johnston WT, Lightfoot TJ, Simpson J, Roman E. Childhood cancer survival: a report from the United Kingdom Childhood Cancer Study. Cancer Epidemiol 2010;34:659-66.
DOI: https://doi.org/10.1016/j.canep.2010.06.020
Healy J, Richer C, Bourgey M, et al. Replication analysis confirms the association of ARID5B with childhood Bcell acute lymphoblastic leukemia. Haematologica 2010;95:1608.
DOI: https://doi.org/10.3324/haematol.2010.022459
Brisson GD, Alves LR, Pombo-de-Oliveira MS. Genetic susceptibility in childhood acute leukaemias: a systematic review. Ecancermedicalscience 2015;9.
DOI: https://doi.org/10.3332/ecancer.2015.539
Jawaid A, Arif K, Amjad N. Clinical Presentations of Acute Leukemia in Pediatric Emergency Department of Pakistan. Bone 2017;29:27.7-3.3.
DOI: https://doi.org/10.15226/2374-8362/4/1/00130
Hussen MMA. Association of Cytochrome P450 2 E1 (C1053T) and NADPH Quinone Oxide Reducatase 1 (C609T)(C 465T) Genes Polymorphism with Acute Lymphoblastic Leukemia in Sudanese Patients. Sudan University of Science & Technology, 2019.
Sultan S, Irfan SM, Parveen S, Mustafa S. Acute lymphoblastic leukemia in adults-an analysis of 51 cases from a tertiary care center in Pakistan. Asian Pac J Cancer Prev 2016;17:2307-9.
DOI: https://doi.org/10.7314/APJCP.2016.17.4.2307
Bazarbashi S, Al Eid H, Minguet J. Cancer incidence in Saudi Arabia: 2012 data from the Saudi cancer registry. Asian Pac J Cancer Prev APJCP 2017;18:2437.
DeSantis C, Siegel R, Jemal A. Cancer treatment and survivorship: facts and figures 2014–2015. Ame Cancer Soc 2014;2015:3-6.
Society AC. Cancer facts & figures. 2008: The Society.
Hanna J. Expression of CD95 in acute lymphocytic leukemia (ALL) in Egyptian children before and after treatment. J Blood Disord Transfus 2015;6:1.
Barakat M, Elkhayat Z, Kholussi N, et al. Monitoring treatment response of childhood acute lymphocytic leukemia with certain molecular and biochemical markers. J Biochem Mol Toxicol 2010;24:343-50.
DOI: https://doi.org/10.1002/jbt.20344
Mahmood N, Shahid S, Bakhshi T, et al. Identification of significant risks in pediatric acute lymphoblastic leukemia (ALL) through machine learning (ML) approach. Med Biol Eng Comput 2020;58:2631-40.
DOI: https://doi.org/10.1007/s11517-020-02245-2
Jaime-Pérez JC, García-Arellano G, Herrera-Harza JL, et al. Revisiting the complete blood count and clinical findings at diagnosis of childhood acute lymphoblastic leukemia: 10-year experience at a single center. Hematol Transfus Cell Ther 2019;41:57-61.
DOI: https://doi.org/10.1016/j.htct.2018.05.010
Moussavi F, Hosseini SN, Saket S, Derakhshanfar H. The First CBC in Diagnosis of childhood acute lymphoblastic leukemia. Int J Med Invest 2014;3:0-0.
Aljaafreh L. Immunophenotypic profile of acute leukemia cases using multicolor flow cytometry; three year experience at King Hussein medical center. JRMS 2015;22: 53-8.
DOI: https://doi.org/10.12816/0013175
Shrestha S, Shrestha J, Pun CB, et al. Immunophenotypic study of acute leukemia by flow cytometry at BPKMCH. J Pathol Nepal 2013;3:345-50.
DOI: https://doi.org/10.3126/jpn.v3i5.7856
Spinelli O, Tosi M, Peruta B, et al. Prognostic significance and treatment implications of minimal residual disease studies in Philadelphia-negative adult acute lymphoblastic leukemia. Mediterr J Hematol Infect Dis 2014;6.
DOI: https://doi.org/10.4084/mjhid.2014.062
Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J 2017;2017.
DOI: https://doi.org/10.1038/bcj.2017.53
Gallegos-Arreola MP, Borjas-Gutiérrez C, Zúñiga-González GM, et al. Pathophysiology of acute lymphoblastic leukemia. Clinical Epidemiology of Acute Lymphoblastic Leukemia-From the Molecules to the Clinic. InTech: Mexico, 2013:43-73.
Pahloosye A, Hashemi AS, Mirmohammadi SJ, Atefi A. Presenting clinical and laboratory data of childhood acute lymphoblastic leukemia. Iran J Pediatr Hematol Oncol 2011;1:71-77.
Dai Q, Zhang G, Yang H, et al. Clinical features and outcome of pediatric acute lymphoblastic leukemia with low peripheral blood blast cell count at diagnosis. Medicine 2021;100.
DOI: https://doi.org/10.1097/MD.0000000000024518
de Sousa DWL, de Almeida Ferreira FV, Cavalcante Félix FH, de Oliveira Lopes. Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival. Rev Bras Hematol Hemoter 2015;37:223-9.
DOI: https://doi.org/10.1016/j.bjhh.2015.03.009
Jaafar FH, Kadhom AE. Expression of CD45, CD34, CD10, and human leukocyte antigen-DR in acute lymphoblastic leukemia. Iraq J Hematol 2018;7:14.
DOI: https://doi.org/10.4103/ijh.ijh_31_17
Koppen IJ, Hermans FJ, Kaspers GJ. Folate related gene polymorphisms and susceptibility to develop childhood acute lymphoblastic leukaemia. Brit J Haematol 2010;148:3-14.
DOI: https://doi.org/10.1111/j.1365-2141.2009.07898.x
Gast A, Bermejo JL, Flohr T, et al. Folate metabolic gene polymorphisms and childhood acute lymphoblastic leukemia: a case–control study. Leukemia 2007;21:320-5.
DOI: https://doi.org/10.1038/sj.leu.2404474
de Jonge R, Tissing WJE, Hooijberg JH, et al. Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia. Blood J Ame Soc Hematol 2009;113:2284-9.
DOI: https://doi.org/10.1182/blood-2008-07-165928
Gra O, Glotov AS, Kozhekbaeva Zhm, et al. Genetic polymorphism of GST, NAT2, and MTRR and susceptibility to childhood acute leukemia. Mol Biol 2008;42: 187-97.
DOI: https://doi.org/10.1134/S0026893308020039
Vijayakrishnan J, Studd J, Broderick P, et al. Genomewide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia. Nat Comm 2018;9:1-9.
DOI: https://doi.org/10.1038/s41467-018-03178-z
Gemmati D, Ongaro A, Scapoli GL, et al. Common gene polymorphisms in the metabolic folate and methylation pathway and the risk of acute lymphoblastic leukemia and non-Hodgkin’s lymphoma in adults. Cancer Epidemiol Biomarkers Prev 2004;13:787-94.
DOI: https://doi.org/10.1158/1055-9965.787.13.5
How to Cite
Edris , M. T., Merghani , M. M., Gafar , S. S., Asmali, A. M., Yasin, E. B., Alserihi , R., Alkhatabi , H., Qutob, H. M., Qahwaji , R., & Ali, E. W. (2023). Association of methionine synthase reductase (MTRR A66G) polymorphism with susceptibility to acute lymphoblastic leukemia. Italian Journal of Medicine, 17(2). https://doi.org/10.4081/itjm.2023.1644
Copyright (c) 2023 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
