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


METHODS
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
M Fatih
MF
Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Selvan
Mano
M
Wang
Li-E
LE
Stout
Linda
L
Erana
Rodrigo
R
Airewele
Gladstone
G
Adatto
Phyllis
P
Hess
Kenneth
K
Ali-Osman
Francis
F
Groves
Morris
M
Yung
Alfred W K
AW
Levin
Victor A
VA
Wei
Qingyi
Q
Bondy
Melissa
M
D000328:Adult; D001254:Astrocytoma / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality*; D004806:Ependymoma / Q000235:genetics; D005260:Female; D005838:Genotype; D005910:Glioma / Q000235:genetics* / Q000401:mortality*; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009837:Oligodendroglioma / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D016016:Proportional Hazards Models; D013997:Time Factors; D016896:Treatment Outcome
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human