期刊
NEUROEPIDEMIOLOGY
卷 32, 期 1, 页码 21-29出版社
KARGER
DOI: 10.1159/000170088
关键词
Glioblastoma; MGMT promoter methylation; MGMT polymorphism; TP53 mutations
资金
- Foundation for Promotion of Cancer Research, Japan
- IARC Postdoctoral Fellowship
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. Copyright (C) 2008 S. Karger AG, Basel
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