Comparison of CYP1A2 and NAT2 phenotypes between black and white smokers

Biochem Pharmacol. 2008 Oct 1;76(7):929-37. doi: 10.1016/j.bcp.2008.07.024. Epub 2008 Jul 25.

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • African Continental Ancestry Group* / genetics
  • Arylamine N-Acetyltransferase / metabolism*
  • Caffeine / pharmacokinetics
  • Caffeine / urine*
  • Cotinine / urine
  • Creatinine / urine
  • Cytochrome P-450 CYP1A2 / metabolism*
  • European Continental Ancestry Group* / genetics
  • Female
  • Glutathione Transferase / genetics
  • Humans
  • Male
  • New York
  • Phenotype
  • Polymorphism, Restriction Fragment Length
  • Smoking / genetics
  • Smoking / metabolism*

Substances

  • Caffeine
  • Creatinine
  • CYP1A2 protein, human
  • Cytochrome P-450 CYP1A2
  • Arylamine N-Acetyltransferase
  • NAT2 protein, human
  • GSTM3 protein, human
  • Glutathione Transferase
  • glutathione S-transferase M1
  • Cotinine