Genetically determined N-acetylation and oxidation capacities in Japanese patients with non-occupational urinary bladder cancer

• Published in: European journal of clinical pharmacology 1989-11, Vol.37 (6), p.581-587
• Main Authors: HORAI, Y, FUJITA, K, ISHIZAKI, T
• Format: Article
• Language: English
• Subjects: Acetylation; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Chi-Square Distribution; Dapsone - analogs & derivatives; Dapsone - blood; Dapsone - metabolism; Disease Susceptibility; Female; General pharmacology; Humans; Japan; Male; Medical sciences; Metoprolol - analogs & derivatives; Metoprolol - blood; Metoprolol - metabolism; Middle Aged; Oxidation-Reduction; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Phenotype; Urinary Bladder Neoplasms - epidemiology; Urinary Bladder Neoplasms - genetics
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/BF00562549

Genetically determined polymorphisms of N-acetylation and oxidative capacity have been studied using dapsone and metoprolol in 51 Japanese patients with spontaneous bladder cancer and 203 healthy control subjects. The results for N-acetylation pharmacogenetics were against the initial expectation that there would be a preponderance of slow acetylators in the cancer group, as 3 such patients (5.9%) were found as compared to 13 (6.4%) in the healthy group. There was no poor metabolizer (PM) of metoprolol in the cancer group, whereas in the healthy group one (0.5%) was a PM. There were no significant differences between the groups in the frequency of slow acetylator and poor oxidiser phenotypes, or in the frequency distribution profiles of acetylation (monoacetyldapsone/dapsone) and oxidative metabolic ratio (log metoprolol/alpha-hydroxymetoprolol). The results indicate that neither N-acetylation nor the debrisoquine/sparteine-type oxidative phenotype and/or capacity represent a genetic predisposition to spontaneous bladder carcinogenesis in Japanese patients. In the normal Japanese population there is a great predominance of rapid acetylators and extensive oxidisers.