Glutathione S-transferase polymorphisms and survival in primary malignant glioma.

نویسندگان

  • M Fatih Okcu
  • Mano Selvan
  • Li-E Wang
  • Linda Stout
  • Rodrigo Erana
  • Gladstone Airewele
  • Phyllis Adatto
  • Kenneth Hess
  • Francis Ali-Osman
  • Morris Groves
  • Alfred W K Yung
  • Victor A Levin
  • Qingyi Wei
  • Melissa Bondy
چکیده

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.

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عنوان ژورنال:
  • Clinical cancer research : an official journal of the American Association for Cancer Research

دوره 10 8  شماره 

صفحات  -

تاریخ انتشار 2004