Association of the CC genotype of the regulatory BCL2 promoter polymorphism (-938C>A) with better 2-year survival in patients with glioblastoma multiforme.
OBJECTIVE
Bcl-2 plays a key role in the downregulation of apoptosis and proliferation and leads to increased chemoresistance in glioblastoma multiforme (GBM). The authors investigated the role of a common regulatory single-nucleotide polymorphism (-938C>A), which is located in the inhibitory P2 promoter of BCL2.


METHODS
Data from 160 patients suffering from GBM were retrospectively evaluated. Study inclusion criteria consisted of available DNA and, in patients still alive, a follow-up of at least 24 months. Results were analyzed with respect to the basic clinical data, type of surgical intervention (gross-total resection [GTR] versus stereotactic biopsy [SB]), adjuvant therapy, MGMT promoter methylation, and survival at the 2-year follow-up.


RESULTS
At the 2-year follow-up, 127 (79.4%) of the 160 patients had died. Kaplan-Meier curves revealed a significantly higher rate of survival for homo- and heterozygous C-allele carriers (p = 0.031). In the GTR group, the survival rate was 47.1% for homozygous C-allele carriers, 32.0% for heterozygous C-allele carriers, and only 21.4% for homozygous A-allele carriers (p = 0.024). The SB group showed no genotype-dependent differences. Multivariable Cox regression revealed that the BCL2 (-938AA) genotype was an independent negative prognostic factor for 2-year survival in the GTR group according to the BCL2 (-938CC) genotype reference group (hazard ratio 2.50, 95% CI 1.14-5.48, p = 0.022).


CONCLUSIONS
These results suggested that the (-938C>A) polymorphism is a survival prognosticator as well as a marker for a high-risk group among patients with GBM who underwent GTR.
Department of Neurosurgery, Medical Faculty, University of Duisburg-Essen, Essen, Germany. elhindy@uk-essen.de
Nicolai
N
El Hindy
Hagen S
HS
Bachmann
Nicole
N
Lambertz
Michael
M
Adamzik
Holger
H
Nückel
Karl
K
Worm
Yuan
Y
Zhu
Ulrich
U
Sure
Winfried
W
Siffert
I Erol
IE
Sandalcioglu
D000328:Adult; D000368:Aged; D000483:Alleles; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012044:Regression Analysis; D015996:Survival Rate; D016896:Treatment Outcome
D019253:Proto-Oncogene Proteins c-bcl-2