Cytochrome P450 2A6 (CYP2A6) is the main nicotine (NIC)-metabolizing enzyme in humans. We investigated the relationships between CYP2A6 genotype, baseline plasma trans- 3′-hydroxycotinine/cotinine (3HC/COT) (a phenotypic marker of CYP2A6 activity), and smoking behavior in African-American light smokers. Cigarette consumption, age of initiation, and dependence scores did not differ among 3HC/COT quartiles or CYP2A6 genotype groups. Slow metabolizers (SMs; both genetic and phenotypic) had significantly higher plasma NIC levels, suggesting that cigarette consumption was not reduced to adjust for slower rates of NIC metabolism. Individuals in the slowest 3HC/COT quartile had higher quitting rates with both placebo and NIC gum treatments (odds ratio 1.85, 95% confidence interval (CI) 1.08-3.16, P = 0.03). Similarly, the slowest CYP2A6 genotype group had higher quitting rates, although this trend did not reach significance (odds ratio 1.61, 95% CI 0.95-2.72, P = 0.08). The determination of the 3HC/COT ratio, and possibly CYP2A6 genotype, may be useful in the future for personalizing the choice of smoking cessation treatment in African-American light smokers.
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We would like to thank Professor Craig Mello for valuable advice throughout this research, Professor Miguel Esteban for manuscripts revision and renal cell line RCC4, Professor Duanqing Pei for the lung cancer cell line 95D. This research was supported by Introduced Innovative R&D Team Program of Guangdong Province (no. 201001Y0104789252), 863 Program of China (no. 2012AA022501), Strategic Emerging Industry Key Technology Project of Guangdong Province (no. 2012A080800006), the National Natural Science Foundation of China (nos. 30870535 and 90913017), the "Hundred Talents Plan" of Guangzhou Municipality and Combination Project of Guangdong Province and the Ministry of Education (no. 2011B090400478).