Association analysis of glutathione-S-transferase P1 (GSTP1) polymorphism with urothelial cancer susceptibility and myelosuppression after M-VAC chemotherapy.
OBJECTIVE
Glutathione-S-transferase P1 (GSTP1) detoxifies a wide range of endogenous and exogenous carcinogens and anticancer agents such as cisplatin and doxorubicin. The aim of this study was to examine the association between GSTP1 polymorphism and both urothelial cancer susceptibility and adverse events of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) chemotherapy in Japanese urothelial cancer patients.


METHODS
This cohort consisted of 179 urothelial cancer patients and 225 healthy controls matched for age and sex. GSTP1 Ile105Val polymorphism was identified by direct sequencing methods. Furthermore, the association of GSTP1 polymorphism and adverse events of M-VAC chemotherapy was investigated.


RESULTS
A similar frequency of GSTP1 Ile105Val allele was observed in the urothelial cancer patients and in the control group. However, when the 46 patients who underwent systemic M-VAC chemotherapy were investigated, significantly more severe toxicity in leukocytopenia (P = 0.044, odds ratio +infinity, 95% confidence interval 0.9203- +infinity) and a prolonged duration of G-CSF administration (P = 0.013, odds ratio 8.625, 95% confidence interval 1.390-89.98) were observed in patients with the Val allele in comparison to those with the Ile allele.


CONCLUSIONS
The GSTP1 Ile105Val polymorphism was not found to be significantly associated with urothelial cancer susceptibility but it may be associated with myelosuppressive adverse events in M-VAC chemotherapy. The 105Val might therefore be a useful marker for predicting myelosuppression in M-VAC chemotherapy.
Yokomizo
Akira
A
Department of Urology, Kyushu University Graduate School of Medical Science, Fukuoka, Japan. yokoa@uro.med.kyushu-u.ac.jp
Yamamoto
Ken
K
Kinukawa
Naoko
N
Tsunoda
Toshiyuki
T
Koga
Hirofumi
H
Naito
Seiji
S
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019459:Urothelium / Q000473:pathology; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
D014747:Vinblastine; D004317:Doxorubicin; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D002945:Cisplatin; D008727:Methotrexate