MTHFR polymorphisms' influence on outcome and toxicity in acute lymphoblastic leukemia patients

Leuk Res. 2007 Dec;31(12):1669-74. doi: 10.1016/j.leukres.2007.03.028. Epub 2007 May 18.

Abstract

Recently the influence of polymorphisms of different genes involved in metabolism of chemoterapic agents have been studied especially in childhood acute lymphoblastic leukemia (ALL). We evaluated the influence of C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) polymorphisms on time to relapse and survival and on methotrexate (MTX) toxicity in 82 ALL adult patients. Relapse free survival and event free survival between homozygous wild-type and variant patients in both polymorphisms were not significantly different. However, we observed an association between 677TT variant and survival in a subset of ALL patients homogenously treated with MTX-based maintenance (p=0.02). In the same subgroup we confirmed the role of 677TT variant on toxicity during MTX treatment (p=0.003).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Drug-Related Side Effects and Adverse Reactions / genetics
  • Female
  • Genotype
  • Humans
  • Male
  • Methotrexate / therapeutic use
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Methylenetetrahydrofolate Reductase (NADPH2) / physiology
  • Middle Aged
  • Point Mutation
  • Polymorphism, Genetic*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality*
  • Recurrence
  • Survival Rate
  • Treatment Outcome

Substances

  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Methotrexate