A variable but significant proportion of urinary bladder cancer can be attributed to occupational and cultural exposure to carcinogenic arylamines. The variable N-acetylation of carcinogenic arylamines by human hepatic enzyme systems, the known genetic regulation and polymorphic distribution of this enzyme activity in humans, and the known enhanced susceptibility of individuals with the genetically distinct "slow acetylator" phenotype to various arylamine toxicities, have prompted examination of possible correlations between human-N-acetyltransferase phenotype and susceptibility to urinary bladder cancer.The hypothesis being tested is as follows: Slow acetylators, by virtue of their reduced abilities to detoxify arylamines by N-acetylation, may be more susceptible to occupation- and smoking-related urinary bladder cancer; they may, therefore, be found in greater percentage in bladder cancer populations than in - nationalitymatched, disease-free control populations. Sulfamethazine phenotyping will be employed to examine well-defined Japanese bladder cancer populations with and without histories of cigarette smoking, and with and without documentable occupational exposure to 4, 4'-diaminobiphenyl (benzidine) or 2-aminophthalene (beta-naphthylamine).The results of these studies are expected to allow assessment of the relationship between arylamine-induced bladder cancer and the slow acetylator phenotype as a determinant of susceptibility, assessment of the feasibility of identifying highly susceptible individuals in high-risk populations.National Cancer Institute (NCI)
