Glutathione S-transferase polymorphisms and survival in primary malignant glioma.
PURPOSE: The purpose of this research was to investigate the relationship between glutathione S-transferase (GST) polymorphisms and survival, and chemotherapy-related toxicity in 278 glioma patients. EXPERIMENTAL DESIGN: We determined genetic variants for GSTM1, GSTT1, and GSTP1 enzymes by PCR and restriction fragment length polymorphisms. We conducted Kaplan-Meier and Cox-proportional hazard analyses to examine whether the GST polymorphisms are related to overall survival, and logistic regression analysis to explore whether the GST polymorphisms are associated with toxicity. RESULTS: For patients with anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, and anaplastic ependymoma (n = 78), patients with GSTP1*A/*A-M1 null genotype survived longer than did the rest of the group (median survival "not achieved," and 41 months, respectively; P = 0.06). Among patients treated with nitrosoureas (n = 108), those with GSTP1*A/*A and GSTM1 null genotype were 5.7 times (95% confidence interval, 0.9-37.4) more likely to experience an adverse event secondary to chemotherapy, compared with the others. CONCLUSIONS: In patients with anaplastic astrocytoma, anaplastic oligodendroglioma, and anaplastic oligoastrocytoma, combination of germ-line GSTP1*A/*A and GSTM1 null genotype confers a survival advantage. Patients with this genotype also have an increased risk of adverse events secondary to chemotherapy that primarily comprised nitrosourea alkylating agents.
Okcu, MF; Selvan, M; Wang, L-E; Stout, L; Erana, R; Airewele, G; Adatto, P; Hess, K; Ali-Osman, F; Groves, M; Yung, AWK; Levin, VA; Wei, Q; Bondy, M
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