A case-control study on the effects of the genetic polymorphisms of N-acetyltransferase 2 and glutathione S-transferase mu and theta on the risk of bladder cancer / 예방의학회지

ABSTRACT

Activities of enzymes involved in the metabolism of various carcinogenic xenobiotics is one of the most important host factors for cancer occurrence. N-acetyltransferase (NAT) and glutathione S-transferases (GST) are enzymes which reduce the toxicity of activated carcinogenic metabolites. Slow N-acetylation and lack of GST mu (GSTM1) were reported as risk factors of bladder cancer. GST theta (GSTT1), which is another type of GST, was reported to be deleted at higher proportion among Koreans. Since cause of bladder cancer is not fully explained by single risk factor, many kinds of enzymes would be involved in the metabolism of carcinogens excreted in urine. This study was performed to investigate whether the polymorphisms of NAT2, GSTM1 and GSTT1 are risk factors of bladder cancer and to evaluate the effects of their interaction on bladder cancer development. Sixty-seven bladder cancer and 67 age- and sex-matched non-cancer patients hospitalized in Chungbuk National University Hospital from March to December 1996, are the subjects of this case-control study. Questionnaire interview was done and the genotypes of NAT2, GSTM1 and GSTT1 were identified using PCR methods with DNA extracted from venous blood. The effects of the polymorphism of NAT2 and GSTM1 and their interaction on bladder cancer were statistically tested after controlling the other risk factors. The frequencies of slow, intermediate, and rapid acetylators were 3.0%, 38.8%, and 58.2% for the cases, and 7.6%, 40.9%, and 51.5% for the controls, respectively. The risk of bladder cancer was not associated with the increase of NAT2 activity(x(2) trend=l.18, P-value>0.05). GSTM1 was deleted in 68.7% of the cases and 49.3% of the controls (x(2)=5.21, P-value<0.05), and the odds ratio (95% CI) was 2.23 (l.12 - 4.56). GSTT1 deletion, the rate of which were 26.9% for the bladder cancer patients and 43.3% for the controls, was a significant protective factor against bladder cancer. Smoking history, turned out to be insignificant as a risk factor of bladder cancer (OR=l.85, 95% CI 0.85 - 4.03), and occupation could not be tested because of the extremely small number of occupational history related to the increase of bladder cancer. In multiple logistic analysis controlling the effects of other risk factors, GSTM1 deletion was the only significant risk factor for bladder cancer (OR 2.56, 95% CI l.22-5.36, P-value<0.05), but slow acetylation and GSTT1 deletion were not. These results suggest that GSTM1 deletion may, be a significant risk factor of bladder cancer. Since there have been much debates on causal relationship between slow acetylation and GSTT1 deletion, and bladder cancer, further studies are needed.