Journal article
Comparison of CYP1A2 and NAT2 phenotypes between black and white smokers
Biochemical pharmacology, Vol.76(7), pp.929-937
2008
Handle:
https://hdl.handle.net/2376/116035
PMCID: PMC2597011
PMID: 18703023
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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Details
- Title
- Comparison of CYP1A2 and NAT2 phenotypes between black and white smokers
- Creators
- Joshua E Muscat - Penn State Cancer Institute, Department of Public Health Sciences, Penn State University College of Medicine, Hershey, PA 17036, United StatesBrian Pittman - Yale University School of Medicine, New Haven, CT 06510, United StatesWayne Kleinman - Department of Neurology and Neuroscience, Cornell University Medical Center, Burke Medical Research Institute, White Plains, NY 10605, United StatesPhilip Lazarus - Penn State Cancer Institute, Department of Pharmacology, Penn State University College of Medicine, Hershey, PA 17036, United StatesSteven D Stellman - Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United StatesJohn P Richie - Penn State Cancer Institute, Department of Public Health Sciences, Penn State University College of Medicine, Hershey, PA 17036, United States
- Publication Details
- Biochemical pharmacology, Vol.76(7), pp.929-937
- Academic Unit
- Pharmaceutical Sciences, Department of
- Publisher
- Elsevier Inc
- Identifiers
- 99900547332701842
- Language
- English
- Resource Type
- Journal article