Journal
EUROPEAN JOURNAL OF CANCER
Volume 49, Issue 14, Pages 3010-3019Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2013.05.019
Keywords
Bladder cancer; Epidemiology; Glutathione S-transferase; GSTT1; Polymorphism; Prognosis
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Funding
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science, and Technology of Korea [2012-0000476, 2012R1A1A4A01008753]
- Rural Development Administration, Republic of Korea [PJ009621]
- National Research Foundation of Korea [2012R1A1A4A01008753] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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