Additional genetic risk factor for death in children with acute lymphoblastic leukemia: a common polymorphism of the MTHFR gene

Pediatr Blood Cancer. 2009 Mar;52(3):364-8. doi: 10.1002/pbc.21815.

Abstract

Background: The presence of metabolically important genetic polymorphisms may affect treatment efficacy in patients with malignancies. The objective of this prospective multicenter study was to evaluate the role of selected polymorphisms of genes associated with metabolism of chemotherapeutic drugs as prognostic markers in children with acute lymphoblastic leukemia.

Procedure: Genotyping for the presence of 7 genetic variants in 403 patients and analysis of death cases were performed.

Results: Thirty-one children died before reaching remission maintenance phase. Genetic analysis revealed in this group increased frequency of homozygosity for c.677C>T polymorphism of the MTHFR gene (26% vs. 8% in the survivors; OR 4.09; 95% CI 1.67-10; adjusted for multiple testing P = 0.028).

Conclusion: Our data suggest that modification of anti-leukemic treatment should be considered in patients homozygous for c.677C>T polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5,10-Methylenetetrahydrofolate Reductase (FADH2) / genetics*
  • 5,10-Methylenetetrahydrofolate Reductase (FADH2) / metabolism
  • Adolescent
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Infant
  • Male
  • Polymorphism, Genetic / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / enzymology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality*
  • Risk Factors

Substances

  • 5,10-Methylenetetrahydrofolate Reductase (FADH2)