Nicotine Metabolism in Three Ethnic/Racial Groups with Different Risks of Lung Cancer
- 1 December 2008
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Epidemiology, Biomarkers & Prevention
- Vol. 17 (12), 3526-3535
- https://doi.org/10.1158/1055-9965.epi-08-0424
Abstract
Previously, we documented that smoking-associated lung cancer risk is greater in Hawaiians and lower in Japanese compared with Whites. Nicotine metabolism by cytochrome P450 2A6 (CYP2A6) varies across ethnicity/race and is hypothesized to affect smoking behavior. We investigated whether higher CYP2A6 activity results in the smoker extracting more nicotine (adjusting for cigarettes per day) and being exposed to higher levels of tobacco-specific nitrosamine [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)] and pyrene, a representative polycyclic aromatic hydrocarbon. We conducted a cross-sectional study of 585 smokers among the three main ethnic/racial groups in Hawaii and examined whether differences in CYP2A6 activity correlate with the ethnic/racial differences in lung cancer risk. We assessed CYP2A6 activity by nicotine metabolite ratio (total trans-3-hydroxycotinine/total cotinine) and caffeine metabolite ratio (1,7-dimethyl uric acid/1,7-dimethylxanthine) in 12 h urine. We also measured urinary nicotine equivalents (sum of nicotine, cotinine, and trans-3-hydroxycotinine and their respective glucuronides), a marker of nicotine dose, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronide, markers of NNK exposure, and 1-hydroxypyrene, a marker of pyrene exposure. The nicotine metabolite ratio was higher in Whites than in Japanese and intermediate in Hawaiians (P values < 0.05). Cigarettes per day-adjusted nicotine equivalents were lower in Japanese compared with Hawaiians or Whites (P = 0.005 and P < 0.0001, respectively) and greater in men than women (P < 0.0001). Nicotine equivalents and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol increased with CYP2A6 activity, indicating that smokers with greater nicotine metabolism smoke more extensively and have a higher internal NNK dose. The particularly low nicotine metabolism of Japanese smokers may contribute to their previously described decreased lung cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3526–35)Keywords
This publication has 48 references indexed in Scilit:
- Human CYP2A6 Is Induced by Estrogen via Estrogen ReceptorDrug Metabolism and Disposition, 2007
- Smoking and Colorectal Cancer: Different Effects by Type of Cigarettes?Cancer Epidemiology, Biomarkers & Prevention, 2007
- Urine Nicotine Metabolites and Smoking Behavior in a Multiracial/Multiethnic National Sample of Young AdultsAmerican Journal of Epidemiology, 2007
- CYP2A6 IS A PRINCIPAL ENZYME INVOLVED IN HYDROXYLATION OF 1,7-DIMETHYLXANTHINE, A MAIN CAFFEINE METABOLITE, IN HUMANSDrug Metabolism and Disposition, 2005
- Metabolism and Disposition Kinetics of NicotinePharmacological Reviews, 2005
- Fruits, vegetables and lung cancer: A pooled analysis of cohort studiesInternational Journal of Cancer, 2003
- Accelerated Metabolism of Nicotine and Cotinine in Pregnant SmokersThe Journal of pharmacology and experimental therapeutics, 2002
- Cigarette smoking and subsequent risk of lung cancer by histologic type in middle‐aged Japanese men and women: The JPHC studyInternational Journal of Cancer, 2002
- Tobacco Smoke Carcinogens and Lung CancerJNCI Journal of the National Cancer Institute, 1999
- Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolitesPharmacogenetics, 1992