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Eur J Cancer. 2013 Sep;49(14):3010-9. doi: 10.1016/j.ejca.2013.05.019. Epub 2013 Jun 26.

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

Author information

1
Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.

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.

KEYWORDS:

Bladder cancer; Epidemiology; GSTT1; Glutathione S-transferase; Polymorphism; Prognosis

PMID:
23810248
DOI:
10.1016/j.ejca.2013.05.019
[Indexed for MEDLINE]

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