Effects of Smoking and Polymorphisms of Glutathione S-Transferase M1 and T1 as Risk Factors on the Development of Bladder Cancer

Shin, Kwan Hee; Lee, Sang Cheol; Kim, Wun Jae

Abstract

PURPOSE: To determine if the smoking status and polymorphisms of the glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genes were risk factors for bladder tumor and to evaluate the effects of their interaction on bladder tumor development.
MATERIALS AND METHODS
One hundred and six patients with bladder cancer and 212 age- and sex-matched controls were enrolled in this study. Their smoking status was obtained from a self-completed questionnaire. The GSTM1 and GSTT1 polymorphisms were analyzed using a multiplex polymerase chain reaction (PCR) from the isolated genomic DNA.
RESULTS
Smoking status was a strong risk factor for the development of bladder tumor (OR: 3.05, 95% CI: 1.46-6.34, p=0.001). The bladder tumor risk increased in the GSTM1-null genotype compared with the GSTM1-positive genotype (OR: 1.67, 95% CI: 1.02-2.72, p=0.041). On the other hand, the GSTT1-null genotype had significant protective effect against bladder tumor development (OR: 0.57, 95% CI: 0.35-0.91, p= 0.019). The GSTM1-null/GSTT1-positive genotypes had a significant risk factor for bladder tumors compared to the GSTM1-positive/GSTT1-null genotypes (OR: 3.05, 95% CI: 1.46-6.34, p=0.002). Smokers with the GSTM1-null/GSTT1-positive genotypes had a five-fold higher risk for developing bladder tumors than non-smokers with the same genotype and a nine-fold higher risk than non-smokers with the GSTM1-positive/ GSTT1-null genotypes (p=0.001). The GSTM1-null genotype in smokers also correlated with superficial bladder cancer (OR: 2.74, 95% CI: 1.01-7.41, p=0.04).
CONCLUSIONS
Smoking is an independent risk factor for the development of bladder tumors in Korean, and the GSTM1-null and GSTT1-positive genotypes in smokers are important host risk factors. Therefore, smoking cessation particularly in individuals with the GSTM1-null/GSTT1-positive genotypes may prevent bladder tumor development.