Glutathione S-transferase M1 and T1 polymorphisms: Susceptibility and outcomes in muscle invasive bladder cancer patients

Title
Glutathione S-transferase M1 and T1 polymorphisms: Susceptibility and outcomes in muscle invasive bladder cancer patients
Author(s)
송필현강호원[강호원]하윤석[하윤석]김원태[김원태]김용준[김용준]윤석중[윤석중]이상철[이상철]최영현[최영현]문성권[문성권]김원재[김원재]
Keywords
CELL LUNG-CANCER; PLATINUM-BASED CHEMOTHERAPY; RETRACTED ARTICLE. SEE; UROTHELIAL CARCINOMA; BREAST-CANCER; DNA-REPAIR; SURVIVAL; GSTT1; GSTM1; CISPLATIN
Issue Date
201309
Publisher
ELSEVIER SCI LTD
Citation
EUROPEAN JOURNAL OF CANCER, v.49, no.14, pp.3010 - 3019
Abstract
Background: We investigated whether genetic polymorphisms in the glutathione S transferase mu (GSTM1) and theta (GSTT1) genes modulated risk, disease progression and survival in primary muscle invasive bladder cancer (MIBC). Methods: GSTM1 and GSTT1 polymorphisms were analysed by multiplex polymerase chain reaction (PCR) using blood genomic DNA in 110 MIBC patients and 220 gender- and age-matched healthy controls. The influence of the genetic polymorphisms on patient survival was evaluated by Kaplan-Meier survival curves and Cox Proportional Hazard models. We also evaluated whether cigarette smoking and treatment modality modified the association between genotype and prognosis. Results: GSTM1-null individuals exhibited increased risk for MIBC and an association with cigarette smoking. GSTT1-null subjects showed significant disease progression and cancer-specific death. In the combined analysis, GSTT1-null genotype was an independent risk factor for disease progression and cancer specific death regardless of GSTM1 genotype. Significant differences in progression-free survival (PFS) and cancer-specific survival (CSS) were seen based on GSTT1 genotype. The survival impact of the GSTT1 genotype was only valid for smokers. The GSTT1-null genotype was an independent prognostic factor for shorter PFS in patients who received chemotherapy and those who did not undergo radical cystectomy. By multivariate Cox regression analysis, GSTT1-null genotype was a predictive factor for disease progression and cancer specific survival regardless of treatment modality. Conclusions: The GSTM1-null genotype plays an important role in genetic susceptibility to MIBC and the GSTT1-null genotype is associated with disease progression and shorter survival in MIBC. (C) 2013 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/28992http://dx.doi.org/10.1016/j.ejca.2013.05.019
ISSN
0959-8049
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의과대학 > 비뇨기과학교실 > Articles
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