Nakajima Miki
Kanazawa University, Division of Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kakuma-machi, Kanazawa 920-1192, Japan.
Curr Opin Mol Ther. 2007 Dec;9(6):538-44.
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.
吸烟会对人类的中枢和外周神经系统、行为、心血管及内分泌系统产生复杂的影响,并且是多种癌症的主要风险因素。尼古丁是烟草的主要成分,是导致烟草依赖形成和维持的化合物。人体肝脏中的CYP2A6可将吸收的尼古丁迅速且广泛地代谢为无活性的可替宁,这对尼古丁的清除有重大影响。在理解尼古丁代谢的个体间差异与CYP2A6基因多态性之间的关系方面已取得进展。最近的研究结果增加了我们对CYP2A6变体的等位基因频率、尼古丁代谢和癌症风险的种族差异的认识。在这篇综述中,还讨论了CYP2A6基因多态性与吸烟行为或癌症风险之间的潜在关联。