Glutathione S‐transferase polymorphisms are associated with survival in anaplastic glioma patients

Abstract

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. The medical records of 207 patients with AG from a single cancer center were reviewed retrospectively. Polymorphisms for the GST micro1 (GSTM1), GST theta1 (GSTT1), and GST pi1 (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. 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. 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.