Glutathione S-transferase polymorphisms and ovarian cancer treatment and survival.
OBJECTIVE
Members of the glutathione S-transferase (GST) family have been shown to have functional polymorphisms that may affect drug metabolism and influence the effects of chemotherapy and survival from cancer. GSTM1, GSTT1, and GSTP1 genotypes were evaluated for their role in ovarian cancer treatment and survival.


METHODS
DNA was extracted from tumor tissues of 215 patients diagnosed with primary epithelial ovarian cancer. GSTM1 and GSTT1 genotypes were determined by multiplex PCR; GSTP1 genotypes were assessed with PCR-RFLP. Associations between GST polymorphisms and risk of ovarian cancer progression or death were analyzed using Cox proportional hazards regression; subgroups of patients receiving different chemotherapeutics were also evaluated.


RESULTS
GST polymorphisms were not found to be associated with patient or tumor characteristics or response to treatment. However, GSTM1 null patients were less likely to have disease progression (HR: 0.65, 95% CI: 0.43-0.99) or to die (HR: 0.68, 95% CI: 0.45-1.03) compared to patients with GSTM1. Patients with GSTM1 null and GSTP1 ile/val or val/val (reduced function) had a further reduction in risk of disease progression compared to patients with GSTM1 or GSTP1 ile/ile (HR: 0.42, 95% CI: 0.24-0.75). A similar association was also suggested for overall survival (HR: 0.61, 95% CI: 0.36-1.05). Subgroup analyses indicated that the effects of GST on survival were more pronounced among patients treated with specific chemotherapeutics.


CONCLUSIONS
These findings support the idea that reduced GST function may improve ovarian cancer survival after post-operative chemotherapy; evaluation of GST functional polymorphisms may help to predict ovarian cancer prognosis.
Beeghly
A
A
Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, 60 College Street, New Haven, CT 06520-8034, USA.
Katsaros
D
D
Chen
H
H
Fracchioli
S
S
Zhang
Y
Y
Massobrio
M
M
Risch
H
H
Jones
B
B
Yu
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016190:Carboplatin / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D011110:Polymorphism, Genetic
D016190:Carboplatin; D002945:Cisplatin; D003520:Cyclophosphamide; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human