Smoking behavior and related cancers: the role of CYP2A6 polymorphisms.
Smoking exerts complex central and peripheral nervous system, behavioral, cardiovascular, and endocrine effects in humans and is a primary risk factor for various cancers. Nicotine, a major constituent of tobacco, is the compound that is responsible for the development and maintenance of tobacco dependence. The absorbed nicotine is rapidly and extensively metabolized to inactive cotinine by CYP2A6 in human livers, which has a major impact on nicotine clearance. Progress has been made in understanding the relationship between the inter-individual variability in nicotine metabolism and genetic polymorphisms of CYP2A6. Recent findings have increased our knowledge concerning ethnic differences in the allele frequencies of the CYP2A6 variants, nicotine metabolism, and cancer risk. In this review, the potential associations between the CYP2A6 polymorphisms and smoking behavior or the risk of cancer are also discussed.
Kanazawa University, Division of Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kakuma-machi, Kanazawa 920-1192, Japan. nmiki@kenroku.kanazawa-u.ac.jp
Miki
M
Nakajima
D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D008099:Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D009538:Nicotine / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D014029:Tobacco Use Disorder / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*
D009538:Nicotine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6