Article
Association of the CC genotype of the regulatory Bcl-2 promoter polymorphism (-938C>A) with better 2-year survival in patients with glioblastoma multiforme
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Published: | September 16, 2010 |
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Objective: Bcl-2 plays a key role in the downregulation of apoptosis and proliferation, as well as increased chemoresistance in glioblastoma multiforme (GBM). We investigated the role of a common regulatory single-nucleotide polymorphism (-938C>A) which is located in the inhibitory P2 promoter of Bcl-2.
Methods: 160 patients suffering from GBM were retrospectively investigated. Inclusion criteria were availability of DNA and for patients still alive a follow-up of at least 24 months. The results were evaluated with respect to the basic clinical data, type of surgical intervention (gross total resection versus biopsy), adjuvant therapy, MGMT-promoter methylation as well as survival at the 2-year follow-up.
Results: At the two-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 gross total resection subgroup the survival rate was 47.1% for homozygous C-allele carriers, 32.0% for heterozygous C-allele carriers, but only 21.4% for homozygous A-allele carriers (p=0.024). The stereotactic-biopsy subgroup showed no genotype-dependent differences. Multivariable Cox regression identified the Bcl-2 (-938AA) genotype as an independent negative prognostic factor for 2-year survival in the gross total resection subgroup according to the Bcl-2 (-938CC) genotype reference group (hazard ratio, 2.5; 95% CI, 1.1–5.5; p=0.022).
Conclusions: These results suggest the (-938C>A) polymorphism as a survival prognosticator as well as a marker for a high-risk group within patients with GBM and gross total resection.