J Cancer Res Clin Oncol (2010) 136:1423–1429 DOI 10.1007/s00432-010-0797-8 123 ORIGINAL PAPER Association of the GNB3 825T-allele with better survival in patients with glioblastoma multiforme Nicolai El Hindy · Michael Adamzik · Nicole Lambertz · Hagen S. Bachmann · Karl Worm · Rupert Egensperger · Ulrich H. Frey · Siamak Asgari · Ulrich Sure · Winfried SiVert · I. Erol Sandalcioglu Received: 29 June 2009 / Accepted: 20 January 2010 / Published online: 10 February 2010  Springer-Verlag 2010 Abstract Purpose Genotypes of the C825T polymorphism of the GNB3 gene encoding the G protein 3 subunit were recently associated with the prognosis of diVerent maligno- mas. We investigated potential associations of GNB3 geno- types with survival of patients with glioblastoma multiforme (GBM). Methods One hundred and sixty-one patients suVering from GBM were retrospectively investigated. Inclusion cri- teria were availability of DNA and a follow-up of at least 24 months. The results were evaluated with respect to the basic clinical data, type of surgical intervention, MGMT promoter methylation, adjuvant therapy, and survival. Results After 2 years of Wrst diagnosis, 128 (79.5%) of the 161 patients had died, 33 (20.5%) were alive. Kaplan–Meier curves revealed a signiWcant higher rate of survival for homo- and heterozygous T-allele carriers (P = 0.019) with 38.5 and 25.3%, respectively, but only 11.6% for homozygous C-allele carriers. Multivariable Cox regression identi Wed the heterozygous (hazard ratio 3.3, 95% CI 1.3–8.0, P = 0.010), as well as homozygous GNB3 825 C-allele (hazard ratio 3.7, 95% CI 1.5–9.1, P = 0.004) as an independent negative prognostic factor for 2-year survival according to the GNB3 825 TT geno- type reference group. Conclusions Our data suggest an association of the GNB3 825TT genotype and better survival in patients with GBM. Keywords Glioblastoma multiforme · Genes · GNB3 · Signal transduction · G protein Purpose Glioblastoma multiforme (GBM) is the most common and most malignant primary brain tumor with an incidence of 7.3/100,000 persons/year in the USA (Demuth and Berens 2004; Kleihues et al. 2002). Most of the glioblastomas are primary or de novo glioblastomas. They develop in older patients and present at diagnosis as full-blown tumors, without clinical, radiological, or histopathological evidence of a less-malignant precursor lesion (Ohgaki et al. 2004; Ohgaki and Kleihues 2005a). Secondary glioblastomas are found in younger patients; they develop slowly through progression from low-grade diVuse (WHO grade II) or anaplastic (WHO grade III) astrocytomas (Ohgaki et al. 2004; Ohgaki and Kleihues 2005a, b). N. El Hindy (&) · N. Lambertz · S. Asgari · U. Sure · I. E. Sandalcioglu Department of Neurosurgery, University Hospital, University of Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany e-mail: nicolai.elhindy@uk-essen.de M. Adamzik · U. H. Frey Department of Anaesthesiology and Intensive Care Medicine, University of Duisburg-Essen, Essen, Germany H. S. Bachmann · W. SiVert Institute of Pharmacogenetics, University of Duisburg-Essen, Essen, Germany K. Worm · R. Egensperger Institute of Pathology and Neuropathology, Medical Faculty, University of Duisburg-Essen, Essen, Germany R. Egensperger Center for Neuropathology and Prion Research, Ludwig Maximilians University of Munich, Munich, Germany