ACETYLATOR PHENOTYPE, AMINOBIPHENYL-HEMOGLOBIN ADDUCT LEVELS, AND BLADDER-CANCER RISK IN WHITE, BLACK, AND ASIAN MEN IN LOS-ANGELES, CALIFORNIA

Background: There is a large body of epidemiologic and experimental da ta that have identified a number of arylamines as human bladder carcin ogens. Metabolic activation is required to biotransform these arylamin es into their carcinogenic forms, and N-hydroxylation, which is cataly zed by the hepatic cytochrome P4501A2 isoenzyme, is generally viewed a s the first critical step. On the other hand, the N-acetylation reacti on, catalyzed by the hepatic N-acetyltransferase enzyme, represents a detoxification pathway for such compounds. The N-acetyltransferase enz yme is coded by a single gene displaying two phenotypes, slow and rapi d acetylators. In the United States, cigarette smoking is a major caus e of bladder cancer in men, and carcinogenic arylamines present in cig arette smoke are believed to be responsible for inducing bladder cance r in smokers. Purpose: Our purpose was to test the differences in thre e ethnic/racial groups for the prevalence of acetylator phenotypes and to ascertain whether slow acetylators actually have higher levels of activated arylamines in comparison with rapid acetylators. Methods: On e hundred thirty-three male residents of Los Angeles County who were e ither white, black, or Asian (Chinese or Japanese) and over the age of 35 years were assessed for their acetylator phenotype and levels of 3 - and 4-aminobiphenyl (ABP) hemoglobin adducts. Subjects were either l ifetime nonsmokers (n = 72) or current cigarette smokers of varying in tensity (n = 61). Results: The proportion of slow acetylators was high est among whites (54%), intermediate among blacks (34%), and lowest am ong Asians (14%). Similarly, geometric mean levels of both 3- and 4-AB P-hemoglobin adducts were highest in whites (1.80 and 49.2 pg/g hemogl obin Hb, respectively), intermediate in blacks (1.54 and 38.5 pg/g H b), and lowest in Asians (0.73 and 36.0 pg/g Hb). As expected, cigaret te smokers had significantly higher mean levels of both 3- and 4-ABP-h emoglobin adducts relative to nonsmokers, and the levels increased wit h the number of cigarettes smoked per day (P<.0005 for both adducts). Slow acetylators consistently exhibited higher mean levels of ABP-hemo globin adducts relative to rapid acetylators, independent of race and level of smoking. Conclusion: The present cross-sectional survey suppo rts acetylation phenotype as an important determinant of bladder cance r risk and a possible major factor in the varying bladder cancer risk among whites, blacks, and Asians.