Glutathione S‐transferase polymorphisms are associated with survival in anaplastic glioma patients |
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| Authors: | M. Fatih Okcu MD MPH Tao Wang MS Yumei Cao MS Amy Renfro‐Spelman MPH Kenneth D. Aldape MD Mark R. Gilbert MD Melissa Bondy PhD |
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| Affiliation: | 1. Department of Pediatrics, Baylor College of Medicine, Houston, Texas;2. Childhood Cancer Prevention and Epidemiology Center, Houston, Texas;3. Texas Children's Cancer Center, Baylor College of Medicine, Houston, TexasThe first 2 authors contributed equally to this article.Fax: (832) 825‐1503;4. Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas;5. Department of Epidemiology, Division of Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas;6. Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas;7. Department of Neuro‐Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas;8. Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas |
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| Abstract: | BACKGROUND: Glutathione S‐transferases (GSTs) are polymorphic enzymes that are responsible for glutathione conjugation of alkylators and scavenging of free radicals created by radiation. GST polymorphisms may result in altered or absent enzyme activity and have been associated with survival in patients with cancer. The authors of this report hypothesized that patients with anaplastic glioma (AG) who have GST genotypes that encode for lower activity enzymes will have longer survival than similar patients who have higher activity genotypes. The current study was performed to investigate the role of GST enzyme polymorphisms in predicting the survival of patients with AG. METHODS: The medical records of 207 patients with AG from a single cancer center were reviewed retrospectively. Polymorphisms for the GST μ1 (GSTM1), GST θ1 (GSTT1), and GST π1 (GSTP1) enzymes were identified. Overall survival was compared using the Kaplan‐Meier method and Cox proportional hazards analyses adjusting for age, sex, histology, and therapy. RESULTS: Among the patients with oligodendroglial tumors (n = 94), patients who had the GSTT1 null genotype had a 2.9 times increased risk of death (95% confidence interval [CI], 1.3‐6.3) compared with patients who had the GSTT1 non‐null genotype. Adjustment for 1p/19q status did not change the finding. In the patients who had anaplastic astrocytoma (n = 113), the patients with all GSTP1 genotypes except GSTP1 *B/*B had a 3.8 times increased risk of death (95% CI, 0.5‐29.6) compared with patients who had the GSTP1 *B/*B genotype. CONCLUSIONS: In patients with anaplastic oligodendroglial tumors, the GSTT1 null genotype may be associated with poor survival, possibly because of modifications in therapy secondary to increased toxicity. This hypothesis is under investigation. In patients with anaplastic astrocytoma, the GSTP1 *B/*B genotype may confer a survival advantage. Cancer 2010. © 2010 American Cancer Society. |
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| Keywords: | pharmacogenetics glutathione S‐transferase polymorphisms anaplastic glioma survival |
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