Polymorphisms involved in folate metabolism pathways and the risk of the development of childhood acute leukemia

Genet Test Mol Biomarkers. 2013 Feb;17(2):147-52. doi: 10.1089/gtmb.2012.0174.

Abstract

Objective: Polymorphisms that reduce the activity of reduced folate carrier (RFC) and methylenetetrahydrofolate reductase (MTHFR) and double (2R2R) or triple (3R3R) 28-bp tandem repeats in the promoter region of thymidylate synthase (TS) have been associated with the risk of childhood acute leukemia (AL). A case-control genotyping study was conducted in Brazilian children with the aim of investigating RFC, MTHFR, and TS polymorphisms as risk factors.

Methods: The polymerase chain reaction-restriction fragment length polymorphism method was employed in 177 AL cases and 390 controls.

Results: The presence of the mutant 1298C, also RFC 80A, was linked to a decreased risk of developing acute lymphoid leukemia (ALL) (odds ratio (OR)=0.46, 95% confidence interval (CI)=0.30-071 and OR=0.51, 95% CI=0.28-0.0.93, respectively).

Conclusions: The genotype 677 CT was associated with increased risk of developing ALL (OR=1.6, 95% CI=1.1-2.7). Further epidemiological study is needed to unravel the role of complex multiple gene-environment interactions in leukemogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Folic Acid / metabolism*
  • Genotype
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Replication Protein C / genetics*
  • Risk
  • Thymidylate Synthase / genetics*
  • Young Adult

Substances

  • RFC1 protein, human
  • Folic Acid
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Thymidylate Synthase
  • Replication Protein C