J Korean Med Sci.  1994 Dec;9(6):482-489. 10.3346/jkms.1994.9.6.482.

CYP1A2 activity as a risk factor for bladder cancer

• Lee SW
• Jang IJ
• Shin SG
• Lee KH
• Yim DS
• Kim SW
• Oh SJ
• Lee SH

• KMID: 644840
• DOI: http://doi.org/10.3346/jkms.1994.9.6.482

Abstract

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.

Keyword

Theophyline demethylation; lsoniazid acetylation; Metoprolol hydroxylation; CYP1A2; CYP2D6; Bladder cancer

MeSH Terms

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