Genetically determined N-acetylation and oxidation capacities in Japanese patients with non-occupational urinary bladder cancer.
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.
Horai
Y
Y
Division of Clinical Pharmacology, Clinical Research Institute, Tokyo, Japan.
Fujita
K
K
Ishizaki
T
T
D000107:Acetylation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D003622:Dapsone / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008790:Metoprolol / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction; D010641:Phenotype; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics*
C029504:alpha-hydroxymetoprolol; D003622:Dapsone; C018965:monoacetyldapsone; D008790:Metoprolol