Pilot Study of CYP2B6 Genetic Variation to Explore the Contribution of Nitrosamine Activation to Lung Carcinogenesis

International Journal of Molecular Sciences

Catherine A. Wassenaar²  Qiong Dong⁴  Christopher I. Amos³  Margaret R. Spitz¹ 

[1] Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; E-Mail:;Department of Pharmacology and Toxicology, The University of Toronto, Toronto, ON M5S 1A8, Canada; E-Mail:;Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, USA; E-Mail:;Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; E-Mail:

关键词: CYP2B6;    CYP2A6;    CHRNA5-CHRNA3-CHRNB4;    tobacco specific nitrosamines;    lung cancer risk;    genetic variation;   

DOI  :  10.3390/ijms14048381

来源: mdpi

【 摘 要 】

We explored the contribution of nitrosamine metabolism to lung cancer in a pilot investigation of genetic variation in CYP2B6, a high-affinity enzymatic activator of tobacco-specific nitrosamines with a negligible role in nicotine metabolism. Previously we found that variation in CYP2A6 and CHRNA5-CHRNA3-CHRNB4 combined to increase lung cancer risk in a case-control study in European American ever-smokers (n = 860). However, these genes are involved in the pharmacology of both nicotine, through which they alter smoking behaviours, and carcinogenic nitrosamines. Herein, we separated participants by CYP2B6 genotype into a high- vs. low-risk group (*1/*1 + *1/*6 vs. *6/*6). Odds ratios estimated through logistic regression modeling were 1.25 (95% CI 0.68–2.30), 1.27 (95% CI 0.89–1.79) and 1.56 (95% CI 1.04–2.31) for CYP2B6, CYP2A6 and CHRNA5-CHRNA3-CHRNB4, respectively, with negligible differences when all genes were evaluated concurrently. Modeling the combined impact of high-risk genotypes yielded odds ratios that rose from 2.05 (95% CI 0.39–10.9) to 2.43 (95% CI 0.47–12.7) to 3.94 (95% CI 0.72–21.5) for those with 1, 2 and 3 vs. 0 high-risk genotypes, respectively. Findings from this pilot point to genetic variation in CYP2B6 as a lung cancer risk factor supporting a role for nitrosamine metabolic activation in the molecular mechanism of lung carcinogenesis.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland