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Survival Prediction in Patients With Glioblastoma Multiforme by Human Telomerase Genetic Variation

Luo Wang, Qingyi Wei, Li-E Wang, Kenneth D. Aldape, Yumei Cao, M. Fatih Okcu, Kenneth R. Hess, Randa El-Zein, Mark R. Gilbert, Shiao Y. Woo, Sujit S. Prabhu, Greg N. Fuller, Melissa L. Bondy

From the Departments of Epidemiology, Pathology, Biostatistics and Applied Mathematics, Radiation Oncology, Neuro-Oncology, and Neurosurgery, The University of Texas M.D. Anderson Cancer Center; and Department of Pediatrics, Baylor College of Medicine, Houston, TX

Address reprint requests to Melissa L. Bondy, PhD, Department of Epidemiology, Unit 1340, The University of Texas M.D. Anderson Cancer Center, PO Box 301439, Houston, TX 77230-1439; e-mail: mbondy{at}mdanderson.org

PURPOSE: Glioblastoma multiforme (GBM) is the most common and aggressive glioma with the poorest survival. Use of biomarkers for screening patients with GBM may be used to modify treatments and improve outcomes. The level of human telomerase (hTERT) expression is an independent predictor of outcome of many cancers, and a functional variant of hTERT MNS16A (shorter tandem repeats or short [S] allele) is associated with increased hTERT mRNA expression. We investigated whether hTERT MNS16A variant genotype predicted survival in GBM patients.

PATIENTS AND METHODS: We genotyped hTERT MNS16A in 299 GBM patients using polymerase chain reaction and determined hTERT genotype by classifying the DNA band of 243 or 272 base pairs (bp) as S allele and 302 or 333 bp as long (L) allele. We compared overall survival using Kaplan-Meier estimates and equality of survival distributions using the log-rank test, and we computed univariate and multivariate Cox proportional hazards models to estimate the effects of selected variables.

RESULTS: Overall survival differed significantly by hTERT MNS16A genotype, with median survivals of 25.1, 14.7, and 14.6 months for the SS, SL, and LL genotypes, respectively. Compared with the SS genotype, the hazard ratios for the SL and LL genotypes were 1.69 and 1.87, respectively, after adjustment for other factors. Multivariate Cox regression analysis showed an independent statistically significant association between the hTERT MNS16A variant genotype and outcome.

CONCLUSION: A functional hTERT MNS16A genotype is a potential biomarker for assessment of survival outcome of GBM. Larger studies are needed to verify these findings.

Supported in part by National Institutes of Health Grants No. CA-70917 (M.L.B.), ES-11740 and CA-100264 (Q.W.), and CA-16672 (M.D. Anderson Cancer Center).

Presented in part at the 96th Annual Meeting of the American Association for Cancer Research, Anaheim, CA, April 16-20, 2005.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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