CYP1A2, CYP2D6 and N-acetyltransferase activities were estimated in 100 patients with bladder cancer and 84 control subjects from measurements of theophylline, metoprolol and isoniazid and their metabolites in urine, respectively. The frequency of occurrence of slow acetylators of isoniazid and poor metabolizers of metoprolol were 16.7% and 1.2% in the control group and 16.3% and 2.0% in the cancer patient group. These differences were not significant. The recovery ratio of 1-methyluric acid(1-MU) from theophylline was significantly higher in patients with bladder cancer than in control subjects(0.340 +/- 0.016 versus 0.260 +/- 0.020, p< 0.05). The 1-MU recovery ratio was a significant, independent risk factor among the metabolic capacities tested as shown by logistic regression analysis, controlling for N-acetylation of isoniazid, hydroxylation of metoprolol, age, sex, and smoking. We concluded that the capacity for 3-demethylation of theophylline, as a reflection of CYP1A2 activity, is significantly associated with increased risk of nonoccupational urinary bladder cancer.
Acetylation ; Adult ; Aged ; Amines/metabolism ; Bladder Neoplasms/enzymology/*epidemiology ; Carcinoma, Transitional Cell/enzymology/*epidemiology ; Case-Control Studies ; Cytochrome P-450 CYP1A2 ; Cytochrome P-450 CYP2D6 ; Cytochrome P-450 Enzyme System/metabolism/*urine ; Disease Susceptibility ; Enzyme Induction ; Female ; Human ; Isoniazid/*pharmacokinetics ; Korea/epidemiology ; Logistic Models ; Male ; Methylation ; Metoprolol/*pharmacokinetics ; Middle Age ; Mixed Function Oxygenases/metabolism ; Mixed Function Oxygenases/metabolism ; Oxidoreductases/*urine ; Smoking ; Support, Non-U.S. Gov't ; Theophylline/*pharmacokinetics ; Uric Acid/analogs & derivatives/urine