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Original Paper

Promoter Methylation and Polymorphisms of the MGMT Gene in Glioblastomas: A Population-Based Study

Zawlik I.a,1 · Vaccarella S.a · Kita D.a · Mittelbronn M.b · Franceschi S.a · Ohgaki H.a

Author affiliations

aInternational Agency for Research on Cancer, Lyon, France; bDepartment of Neuropathology, University Hospital, Zurich, Switzerland

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Neuroepidemiology 2009;32:21–29

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: June 21, 2008
Accepted: August 29, 2008
Published online: November 08, 2008
Issue release date: December 2008

Number of Print Pages: 9
Number of Figures: 0
Number of Tables: 3

ISSN: 0251-5350 (Print)
eISSN: 1423-0208 (Online)

For additional information: https://www.karger.com/NED

Abstract

O6-methylguanine-DNA methyltransferase (MGMT) is a repair enzyme that removes promutagenic O6-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.

© 2008 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: June 21, 2008
Accepted: August 29, 2008
Published online: November 08, 2008
Issue release date: December 2008

Number of Print Pages: 9
Number of Figures: 0
Number of Tables: 3

ISSN: 0251-5350 (Print)
eISSN: 1423-0208 (Online)

For additional information: https://www.karger.com/NED


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