Original Articles

Reduced folate carrier 1 (RFC1) gene polymorphisms among acute lymphoblastic leukemia patients

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.
Received: 14 September 2024
Published: 26 March 2025
1071
Views
398
Downloads

Authors

Reduced Folate Carrier1 (RFC1) gene’s metabolism is crucial for DNA synthesis, epigenetic mechanisms, and cellular methylation events. Nonetheless, RFC1 polymorphisms have drawn a lot of interest in current medical genetics studies. The objectives of the study were to ascertain the relationship between the risk of Acute Lymphoblastic Leukemia (ALL) in Sudanese patients and the genetic variant of RFC1 (G 80A). Using Real-Time Polymerase Chain Reaction (RT-PCR) method, 150 ALL patients and 150 healthy control volunteers had their DNA collected and examined for the casecontrol study. Version 25 of the Statistical Package for Social Science (SPSS) software was used to analyze the data. There was no discernible difference in the age or gender of the patients compared to the controls. According to flow cytometry data, T-ALL accounts for 31 (21%) and B cell type accounts for 119 (79%). According to this study, there is a statistically significant correlation between the mean blast (p=0.050) and the mean total white blood cell count (p=0.000) in T-ALL cases. The genotype frequency of RFC1 (G80A) was found to be GG 39 (26.0%), GA 41 (27.3%), and 70 (46.7%) for AA in the cases, while GG 41 (27.3%), GA 28 (18.7%), and AA 81 (54.0%) in the control group. While the homozygous genotypes AA and GG were more common in the control group, the heterozygous genotype GA was more common in the patient group. On the other hand, the genotype distribution among the research groups was not statistically significant with odds ratio: 0.745 (0.473- 1.174), p=0.192. In conclusion, RFC1 (G80A) polymorphism was not found to be associated with an increased risk of ALL, according to the findings of this investigation.

Downloads

Download data is not yet available.

Ulrich CM, Curtin K, Potter JD, et al. Polymorphisms in the reduced folate carrier, thymidylate synthase, or methionine synthase and risk of colon cancer. Cancer Epidemiol Biomarkers Prev 2005;14:2509-16.

Eklöf V, Van Guelpen B, Hultdin J, et al. The reduced folate carrier (RFC1) 80G> A and folate hydrolase 1 (FOLH1) 1561C> T polymorphisms and the risk of colorectal cancer: A nested case‐referent study. Scand J Clin Lab Invest 2008;68:393-401.

Curtin K, Ulrich CM, Samowitz WS, et al. Candidate pathway polymorphisms in one-carbon metabolism and risk of rectal tumor mutations. Int J Mol Epidemiol Genet 2011;2:1-8.

Jokić M, Brčić-Kostić K, Stefulj J, et al. Association of MTHFR, MTR, MTRR, RFC1, and DHFR gene polymorphisms with susceptibility to sporadic colon cancer. DNA Cell Biol 2011;30:771-6.

Yiu TT, Li W. Pediatric cancer epigenome and the influence of folate. Epigenomics 2015;7:961-73.

Lv H, Hu S-Y, Du Z-Z, et al. Gene polymorphisms in the folate metabolic pathway and risk of pediatric acute lymphoblastic leukemia: a case-control study in a Chinese population. Int J Clin Exper Pathol 2018;11:1724.

Koppen IJ, Hermans FJ, Kaspers GJ. Folate related gene polymorphisms and susceptibility to develop childhood acute lymphoblastic leukaemia. Br J Haematol 2010;148:3-14.

Matherly LH, Hou Z, Deng Y. Human reduced folate carrier: translation of basic biology to cancer etiology and therapy. Cancer Metastasis Rev 2007;26:111-28.

Kung TN, Dennis J, Ma Y, et al. RFC1 80G> A is a genetic determinant of methotrexate efficacy in rheumatoid arthritis: a human genome epidemiologic review and meta‐analysis of observational studies. Arthritis Rheumatol 2014;66:1111-20.

Yee SW, Gong L, Badagnani I, et al. SLC19A1 pharmacogenomics summary. Pharmacogen Genomics 2010;20:708-15.

Huang X, Gao Y, He J, et al. The association between RFC1 G80A polymorphism and cancer susceptibility: Evidence from 33 studies. J Cancer 2016;7:144.

Shang Y, Zhao H, Niu B, et al. Correlation of polymorphism of MTHFRs and RFC‐1 genes with neural tube defects in China. Birth Defects Res A Clin Mol Teratol 2008;82:3-7.

Pei L, Zhu H, Zhu J, et al. Genetic variation of infant reduced folate carrier (A80G) and risk of orofacial defects and congenital heart defects in China. Ann Epidemiol 2006;16:352-6.

Bi X-H, Zhao H-L, Zhang Z-X, Zhang J-W. Association of RFC1 A80G and MTHFR C677T polymorphisms with Alzheimer's disease. Neurobiol Aging 2009;30:1601-7.

Chango A, Emery-Fillon N, de Courcy GP, et al. A polymorphism (80G-> A) in the reduced folate carrier gene and its associations with folate status and homocysteinemia. Molecular Genet Metab 2000;70:310-5.

Blom HJ, Smulders Y. Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. J Inherited Metab Dis 2011;34:75-81.

de Miranda DO, Barros JE, Vieira MMS, et al. Reduced folate carrier-1 G80a gene polymorphism is associated with neuroblastoma’s development. Molecular Biol Rep 2014;41:5069-75.

Silva RMS, Fontes ACL, Silva KA, et al. Polymorphisms involved in folate metabolism pathways and the risk of the development of childhood acute leukemia. Genet Test Mol Biomarkers 2013;17:147-52.

Montalvao-de-Azevedo R, Vasconcelos GM, Vargas FR, et al. RFC-1 80G> A polymorphism in case-mother/control-mother dyads is associated with risk of nephroblastoma and neuroblastoma. Genet Test Mol Biomarkers 2015;19:75-81.

Jawaid A, Arif K, Amjad N. Clinical presentations of acute leukemia in Pediatric Emergency Department of Pakistan. Bone 2017;29:27.7-3.3.

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 Pacific J Cancer Prev 2016;17:2307-9.

Hussen MMA, Mohamed BA, Ali AW, Altayeb HN. 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. Thesis. Sudan University of Science & Technology. 2019.

Bazarbashi S, Al Eid H, Minguet J. Cancer incidence in Saudi Arabia: 2012 data from the Saudi cancer registry. Asian Pac J Cancer Prev 2017;18:2437.

Nass SJ, Patlak M (Rapporteurs), National Cancer Policy Forum, Board on Health Care Services, Institute of Medicine. Comprehensive cancer care for children and their families: Summary of a Joint Workshop by the Institute of Medicine and the American Cancer Society. Washington: National Academies Press; 2015.

American Cancer Society. Cancer Facts and Figures 2006.

American Cancer Society Atlanta; 2008.

Ebrahim J, Tanious A, Mirgani A, et al. Immunophenotypic features of t cell-acute lymphoblastic leukemia in Sudan. 2017. Available from: https://www.researchgate.net/publication/367165236_IMMUNOPHENOTYPIC_FEATURES_OF_T_CELL-ACUTE_LYMPHOBLASTIC_LEUKEMIA_IN_SUDAN

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, Kholoussi 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.

Mahmood N, Shahid S, Bakhshi T, et al. Identification of significant risks in pediatric acute lymphoblastic leukemia (ALL) through machine learning (ML) approach. Medical Biol Engin Computing 2020;58:2631-40.

Jaime-Pérez JC, García-Arellano G, Herrera-Garza 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.

Moussavi F, Hosseini S, Saket S, Derakhshanfar H. The first CBC in dDiagnosis of childhood acute lymphoblastic leukemia. Int J Med Investigation 2014;3:9-12.

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.

Shrestha S, Shrestha J, Pun C, et al. Immunophenotypic study of acute leukemia by flow cytometry at BPKMCH. J Pathology Nepal 2013;3:345-50.

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:e2014062.

Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J 2017;7:e577.

Gallegos-Arreola M, Borjas-Gutiérrez C, Zúñiga-González G, et al. Pathophysiology of acute lymphoblastic leukemia. INTECH 2013;3:43-60.

Pahloosye A, Hashemi AS, Mirmohammadi SJ, Atefi A. Presenting clinical and laboratory data of childhood acute lymphoblastic leukemia. Iranian J Pediatric Hematol Oncol 2011;1:71-7.

Mushtaq N, Fadoo Z, Naqvi A. Childhood acute iymphoblastic leukaemia: Experience from a single tertiary care facility of Pakistan. J Pakistan Med Assoc 2013;63:1399.

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:e24518.

Sousa DWLd, Ferreira FVdA, Félix FHC, Lopes MVdO. Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival. Revista Brasileira de Hematologia e Hemoterapia 2015;37:223-9.

Jaafar FH, Kadhom AE. Expression of CD45, CD34, CD10, and human leukocyte antigen-DR in acute lymphoblastic leukemia. Iraqi J Hematol 2018;7:14-9.

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.

Gemmati D, Ongaro A, Scapoli, 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.‏

de Jonge R, Tissing WJ, Hooijberg JH, et al. Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia. Blood 2009;113:2284-9.

Vijayakrishnan J, Houlston RS. Candidate gene association studies and risk of childhood acute lymphoblastic leukemia: a systematic review and meta-analysis. Haematologica 2010;95:1405.

How to Cite



Reduced folate carrier 1 (RFC1) gene polymorphisms among acute lymphoblastic leukemia patients. (2025). Journal of Biological Research - Bollettino Della Società Italiana Di Biologia Sperimentale, 98(1). https://doi.org/10.4081/jbr.2025.13105