The effect of RFC G80A polymorphism in Cretan children with acute lymphoblastic leukemia and its interaction with MTHFR C677T and A1298C polymorphisms

Int J Lab Hematol. 2014 Aug;36(4):425-30. doi: 10.1111/ijlh.12160. Epub 2013 Nov 16.

Abstract

Introduction: The association between the risk of acute lymphoblastic leukemia (ALL) in children and enzymes involved in the folate metabolism has been under investigation lately. The reduced folate carrier gene (RFC) encodes reduced folate carrier, a protein that transports into the cell both folate and methotrexate, a commonly used chemotherapeutic drug, has been proved polymorphic at position 80 (G→A). The role of this polymorphism in childhood ALL and its interaction with other enzymes of the folate metabolic pathway, including MTHFR, has been examined in different populations with diverse results.

Methods: In the present case-control study, 35 children with ALL and 48 healthy adult blood donors, all originating from the island of Crete (Greece), were screened for the presence of the RFC G80A polymorphism, using PCR/RFLP techniques. The effect on ALL risk and methotrexate-induced toxicities, along with the role of gene-gene interactions in our population, were examined.

Results: No significant association was observed between the RFC G80A genotypes and either the development of ALL or the presence of adverse events. However, a significant association was detected between the MTHFR A1298C/ RFC G80A genotype and a nonpredisposition for ALL (P = 0.035).

Conclusion: This study suggests that gene-gene interactions in childhood ALL may be of prognostic value in our population.

Keywords: ALL; MTHFR; PCR; RFC; RFLP; SNPs.

MeSH terms

  • Alleles
  • Antimetabolites, Antineoplastic / therapeutic use
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Epistasis, Genetic*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Greece
  • Humans
  • Male
  • Methotrexate / therapeutic use
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Reduced Folate Carrier Protein / genetics*

Substances

  • Antimetabolites, Antineoplastic
  • Reduced Folate Carrier Protein
  • SLC19A1 protein, human
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Methotrexate