"Although cigarette smoke contains diverse carcinogens, PAH, N-nitrosamines, aromatic amines, 1,3-butadiene, benzene, aldehydes, and ethylene oxide are among the most important carcinogens because of their carcinogenic potency and levels in cigarette smoke. Moreover, the major pathways of metabolic activation and detoxification of some of the principal carcinogens in cigarette smoke are well established. Reactive intermediate agents critical in forming DNA adducts include diol epoxides of PAH, diazonium ions generated by ?-hydroxylation of nitrosamines, nitrenium ions formed from esters of N-hydroxylated aromatic amines, and epoxides such as ethylene oxide. Glutathione and glucuronide conjugation play major roles in detoxification of carcinogens in cigarette smoke.
"Familial predisposition and genetic polymorphisms may play a role in tobacco-related neoplasms. Researchers have established cigarette smoking as a major cause of lung cancer; more than 85 percent of lung cancers are attributable to smoking. However, not all smokers develop lung cancer, and lung cancer can arise in lifetime non-smokers. This variation in disease has stimulated interest in molecular epidemiology of genetic polymorphisms, including genes that regulate the cell cycle and genes for carcinogen-metabolizing enzymes that may lead to variations in susceptibility to the carcinogens in tobacco smoke. Studies to date suggest a role for these genetic polymorphisms in the risk of lung and bladder cancer in smokers, and they support the possibility of interactions between genes and smoking status."


US Department of Health and Human Services. "How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General." Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2010, p. 302.