Steven Stellman - Comparison of CYP1A2 and NAT2 phenotypes between black and white smokers

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      Muscat, J. E., Pittman, B., Kleinman, W., Lazarus, P., Stellman,   S. D., Richie, J. P., Jr. 76 (7) 929-37-

      Abstract: The lower incidence rate of   transitional cell carcinoma of the urinary bladder in blacks than   in whites may be due to racial differences in the catalytic   activity of enzymes that metabolize carcinogenic arylamines in   tobacco smoke. To examine this, we compared cytochrome P4501A2   (CYP1A2) and N-acetyltransferase-2 activities (NAT2) in black and   white smokers using urinary caffeine metabolites as a probe for   enzyme activity in a community-based study of 165 black and 183   white cigarette smokers. The paraxanthine (1,7-dimethylxanthine,   17X)/caffeine (trimethylxanthine, 137X) ratio or   [17X+1,7-dimethyluric acid (17U)]/137X ratio was used as an   indicator of CYP1A2 activity. The   5-acetyl-amino-6-formylamino-3-methyluracil   (AFMU)/1-methylxanthine (1X) ratio indicated NAT2 activity. The   odds ratio for the slow NAT2 phenotype associated with black race   was 0.4; 95% confidence intervals 0.2-0.7. The putative combined   low risk phenotype (slow CYP1A2/rapid NAT2) was more common in   blacks than in whites (25% vs. 15%, P<0.02). There were no   significant racial differences in slow and rapid CYP1A2   phenotypes, and in the combined slow NAT2/rapid CYP1A2 phenotype.   Age, education, cigarette smoking amount, body mass index, GSTM1   and GSTM3 genotypes were unrelated to CYP1A2 and NAT2 activity.   Intake of cruciferous vegetables (primarily broccoli), red meat,   carrots, grapefruit and onions predicted CYP1A2 activity either   for all subjects or in race-specific analyses. Carrot and   grapefruit consumption was related to NAT2 activity.   Collectively, these results indicated that phenotypic differences   in NAT2 alone or in combination with CYP1A2 might help explain   the higher incidence rates of transitional cell bladder cancer in   whites.

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