Tobacco carcinogens, their biomarkers and tobacco-induced cancer

Abstract

Tobacco products cause a variety of cancers, including those of the lung, oral cavity, nasal cavity, larynx, oropharynx, hypopharynx, oesophagus, stomach, liver, pancreas, bladder, ureter, kidney and cervix, and myeloid leukaemia. The carcinogens contained in tobacco products are responsible for these cancers. There are more than 60 carcinogens in cigarette smoke and at least 16 in unburned tobacco. Among these, tobacco-specific nitrosamines (such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N′-nitrosonornicotine (NNN)), polycyclic aromatic hydrocarbons (such as benzo[a]pyrene) and aromatic amines (such as 4-aminobiphenyl) seem to have an important role as causes of cancer. Carcinogen biomarkers — DNA adducts, protein adducts and urinary metabolites — provide objective measures of carcinogen uptake and metabolic activation and detoxification in people who use, or are otherwise exposed to, tobacco products. DNA adducts are central to the carcinogenic process as induced by tobacco products. Among carcinogen biomarkers, DNA adducts potentially provide the most direct link to cancer, but there are still significant measurement problems. Protein adducts are useful alternatives to DNA adducts, and in some cases have provided significant mechanistic insights. Urinary metabolites are probably the most practical biomarkers and provide important information about carcinogen dose and metabolism. Carcinogen biomarkers are important in establishing carcinogen dose in people who are exposed to tobacco products and in understanding mechanisms of carcinogenesis, and might ultimately be useful in predicting cancer risk.