Skip to main content
SpringerLink
Log in

MTHFR Gene Polymorphisms and the Risk of Acute Lymphoblastic Leukemia in Adults and Children: A Case Control Study in India

  • Original Article
  • Published:
Indian Journal of Hematology and Blood Transfusion Aims and scope Submit manuscript

Abstract

Genetic polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) gene have been associated with the development of acute leukemias and various malignancies. The role of MTHFR polymorphism in the development of pediatric acute lymphoblastic leukemia (ALL) has been extensively studied among north Indians in various settings, yet its association with acute leukemias remains unresolved. To evaluate the relationship between functional MTHFR polymorphisms, C677T and A1298C and possible effect on risk of ALL in adults and children in North Indian population by comparing them with healthy controls. DNA was isolated from peripheral blood of 184 ALL patients (33 adults, 151 children) and 155 controls and analyzed by a PCR-restriction fragment length polymorphism assay. The frequency of MTHFR 677CT and 1298 AC genotypes were significantly lower among adult ALL cases when compared to the controls. We found a 1.74-fold reduced risk of ALL in individuals with 1298AC polymorphic variant and a 9.17-fold decreased risk of adult ALL. However, no statistically significant difference was evident between the above polymorphisms and susceptibility to ALL in children. Polymorphisms in the MTHFR gene possibly modulate risk of ALL in north Indian adults but not in children, although larger studies are needed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Skibola CF, Smith MT, Kane E, Roman E, Rollinson S, Cartwright RA et al (1999) Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults. Proc Natl Acad Sci USA 96:12810–12815

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Krajinovic M, Lamothe S, Labuda D, Lemieux-Blanchard E, Theoret Y, Moghrabi A et al (2004) Role of MTHFR genetic polymorphisms in the susceptibility to childhood acute lymphoblastic leukemia. Blood 103:252–257

    Article  CAS  PubMed  Google Scholar 

  3. Robien K, Ulrich CM (2003) 5,10-Methylenetetrahydrofolate reductase polymorphisms and leukemia risk: a HuGE minireview. Am J Epidemiol 157:571–582

    Article  PubMed  Google Scholar 

  4. de Jonge R, Tissing WJE, Hooijberg JH, Jansen G, Kaspers GJL, Lindemans J et al (2009) Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia. Blood 113:2284–2289

    Article  PubMed  Google Scholar 

  5. Wiesberg I, Tran P, Christensen B, Sibani S, Rozen R (1998) A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 64:169–172

    Article  Google Scholar 

  6. Franco RF, Simoes BP, Tone LG, Gabellini SM, Zago MA, Falcao RP (2001) The methylenetetrahydrofolate reductase C677T gene polymorphism decreases the risk of childhood acute lymphocytic leukaemia. Br J Haematol 115:616–618

    Article  CAS  PubMed  Google Scholar 

  7. Wiemels JL, Smith RN, Taylor GM, Eden OB, Alexander FE, Greaves MF (2001) Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci USA 98:4004–4009

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Gemmati D, Ongaro A, Scapoli GL et al (2004) Common gene polymorphisms in the metabolic folate and methylation pathway and the risk of acute lymphoblastic leukemia and non-Hodgin’s lymphoma in adults. Cancer Epidemiol Biomarkers Prev 13:787–974

    CAS  PubMed  Google Scholar 

  9. Kamel AM, Moussa HS, Ebid GT, Bu RR, Bhatia KG (2007) Synergistic effect of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms as risk modifiers of pediatric acute lymphoblastic leukemia. J Egypt Natl Canc Inst 19:96–105

    PubMed  Google Scholar 

  10. Ames BN (1999) Cancer prevention and diet: help from single nucleotide polymorphisms. Proc Natl Acad Sci USA 96:12216–12218

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Botto LD, Yang Q (2000) 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol 151:862–877

    Article  CAS  PubMed  Google Scholar 

  12. Matsuo K, Hamajima N, Suzuki R et al (2004) Methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms and reduced risk of malignant lymphoma. Am J Hematol 77:351–357

    Article  CAS  PubMed  Google Scholar 

  13. Chiusolo P, Reddiconto G, Cimino G, Sica S, Fiorini A, Farina G et al (2004) Methylenetetrahydrofolate reductase genotypes do not play a role in acute lymphoblastic leukemia pathogenesis in the Italian population. Haematologica 89:139–144

    CAS  PubMed  Google Scholar 

  14. Reddy H, Jamil K (2006) Polymorphisms in the MTHFR gene and their possible association with susceptibility to childhood acute lymphocytic leukemia in an Indian population. Leuk Lymphoma 47:1333–1339

    Article  CAS  PubMed  Google Scholar 

  15. Schnakenberg E, Mehles A, Cario G, Rehe K, Seidemann K, Schlegelberger B et al (2005) Polymorphism of methylenetetrahydrofolate reductase (MTHFR) and susceptibility to pediatric acute lymphoblastic leukemia in a German study population. BMC Med Genet 6:23

    Article  PubMed Central  PubMed  Google Scholar 

  16. Alcasabas P, Ravindranath Y, Goyette G, Haller A, Del Rosario L, Lesaca-Medina MY et al (2008) 5,10-Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and the risk of acute lymphoblastic leukemia (ALL) in Filipino children. Pediatr Blood Cancer 51:178–812

    Article  PubMed  Google Scholar 

  17. Milne E, de Klerk NH, van Bockxmeer F, Kees UR, Thompson JR, Baker D et al (2006) Is there a folate-related gene-environment interaction in the etiology of childhood acute lymphoblastic leukemia? Int J Cancer 119:229–232

    Article  CAS  PubMed  Google Scholar 

  18. Oh D, Kim NK, Jang MJ, Kim HC, Lee JH, Lee JA et al (2007) Association of the 5,10-Methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) polymorphisms in Korean patients with adult acute lymphoblastic leukemia. Anticancer Res 27:3419–3424

    CAS  PubMed  Google Scholar 

  19. Kim HN, Kim YK, Lee IK, Yang DH, Lee JJ, Shin MH et al (2009) Association between polymorphisms of folate-metabolizing enzymes and hematological malignancies. Leuk Res 33:82–87

    Article  CAS  PubMed  Google Scholar 

  20. Pereira TV, Rudnicki M, Pereira AC, Pombo-de-Oliveira MS, Franco RF (2006) 5,10-Methylenetetrahydrofolate reductase polymorphisms and acute lymphoblastic leukemia risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 15:1956–1963

    Article  CAS  PubMed  Google Scholar 

  21. Sood S, Das R, Trehan A, Ahluwalia J, Sachdeva MU, Varma N et al (2010) Methylenetetrahydrofolate reductase gene polymorphisms: association with risk for pediatric acute lymphoblastic leukemia in north Indians. Leuk Lymphoma 51:928–932

    Article  CAS  PubMed  Google Scholar 

  22. Sadananda MN, Chandy S, Ramachandra N, Appaji L, Aruna BS, Ramaswamy G et al (2010) Methylenetetrahydrofolate reductase gene polymorphisms and risk of acute lymphoblastic leukemia in children. Ind J Cancer 47:40–45

    Article  Google Scholar 

  23. Nikbakht M, MalekZadeh K, Jha AK, Askari M, Marwaha RK, Kaul D et al (2012) Polymorphisms of MTHFR and MTR genes are not related to susceptibility to childhood ALL in North India. Exp Oncol 34:43–48

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Haematology, All India Institute of Medical Sciences, New Delhi, 110029, India

    Sudha Sazawal, Rekha Chaubey, Pawandeep Kaur, Sunita Chikkara, Bijender Kumar, Alakananda Das Gupta & Renu Saxena

  2. Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India

    L. S. Arya

  3. Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India

    Sameer Bakshi & Vinod Raina

Authors
  1. Sudha Sazawal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rekha Chaubey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pawandeep Kaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sunita Chikkara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bijender Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sameer Bakshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L. S. Arya
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vinod Raina
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alakananda Das Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Renu Saxena
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sudha Sazawal.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sazawal, S., Chaubey, R., Kaur, P. et al. MTHFR Gene Polymorphisms and the Risk of Acute Lymphoblastic Leukemia in Adults and Children: A Case Control Study in India. Indian J Hematol Blood Transfus 30, 219–225 (2014). https://doi.org/10.1007/s12288-013-0295-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12288-013-0295-7

Keywords

Search

Navigation