Promoter methylation and polymorphisms of the MGMT gene in glioblastomas: a population-based study

Neuroepidemiology. 2009;32(1):21-9. doi: 10.1159/000170088. Epub 2008 Nov 8.


O(6)-methylguanine-DNA methyltransferase (MGMT) is a repair enzyme that removes promutagenic O(6)-methylguanine adducts in DNA, to protect cells from acquisition of G:C--> A:T mutations. MGMT promoter methylation and polymorphisms may affect MGMT expression and activity. In the present study, we assessed MGMT promoter methylation and polymorphisms (Leu84Phe, Ile143Val, c.-56C>T) in 371 glioblastomas diagnosed at the population level. MGMT methylation was observed in 165 (44%) glioblastomas, with a higher frequency in females than males (53 vs. 39%; p = 0.0106) and in secondary than primary glioblastomas (73 vs. 43%; p = 0.0074). The frequency of TP53 G:C-->A:T mutations in glioblastomas with MGMT methylation was 25%, which was significantly higher than that in glioblastomas with MGMT methylation (16%; Fisher exact test; p = 0.0385). MGMT 143 Val allele in glioblastomas was significantly less frequent than in a healthy European Caucasian population, and was associated with longer survival than those with the MGMT 143 Ile allele (hazard ratio 0.70; 95% CI 0.48-1.01). These results suggest that MGMT methylation may be associated with susceptibility to acquire TP53 G:C-->A:T mutations, and that MGMT polymorphisms may affect the risk and prognosis of glioblastomas.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / genetics
  • DNA Methylation
  • Female
  • Genetic Predisposition to Disease
  • Glioblastoma / enzymology*
  • Glioblastoma / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics
  • O(6)-Methylguanine-DNA Methyltransferase / genetics*
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • Promoter Regions, Genetic / genetics*
  • Risk Factors
  • Tumor Suppressor Protein p53 / genetics


  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • O(6)-Methylguanine-DNA Methyltransferase