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.
Acetylation ; Carcinogens ; Case-Control Studies* ; Chungcheongbuk-do ; DNA ; Genotype ; Glutathione Transferase* ; Glutathione* ; Humans ; Metabolism ; Occupations ; Odds Ratio ; Polymerase Chain Reaction ; Polymorphism, Genetic* ; Surveys and Questionnaires ; Risk Factors ; Smoke ; Smoking ; Urinary Bladder Neoplasms* ; Urinary Bladder* ; Xenobiotics

BACKGROUND AND OBJECTIVES: Nitric oxide (NO) seems to have some potential to play a regulatory role in the airway function and it maybe related to the pathophysiology of several airway diseases. Although the pathophysiology of nasal polyp is poorly understood, a recent study has suggested that airway NO produced from paranasal sinus epithelium where mNOS is expressed constituitively without immunologic stimulation may play a critical role in the genesis of inflammatory nasal disease. MATERIALS AND METHODS: We examined the presence of mNOS and eNOS in the nasal cavity and paranasal sinus mucosa in 10 healthy persons of nasal septal deviation and 20 patients with nasal polyp by immunohistochemical staining using rabbit polyclonal anti- eNOS and anti-mNOS IgG. Relative quantification of eNOS and mNOS was done by RT-PCR. RESULTS: Immunoreactivity to eNOS and mNOS was positive in all nasal polyps and this reactivity was mainly restricted to the epithelial layer. Immunoreactivity to mNOS in the controls was negative for the inferior turbinate. RT-PCR showed more mNOS reactivity in the nasal polyp than in the control (p<0.03). CONCLUSION: These findings reinforce the concept that the epithelial layer is the main locus and mNOS may be one of the potential factors in the pathogenesis of nasal polyp.
Epithelium ; Humans* ; Immunization ; Immunoglobulin G ; Immunohistochemistry ; Mucous Membrane* ; Nasal Cavity ; Nasal Polyps ; Nitric Oxide ; Nitric Oxide Synthase ; Nose Diseases ; Polyps* ; Turbinates