Carcinogen biomarkers related to smoking and upper aerodigestive tract cancer

Abstract

Smoking is the major cause of upper aerodigestive tract cancers. Among the many constituents of tobacco smoke, polynuclear aromatic hydrocarbons and tobacco-specific nitrosamines are strongly implicated as causative factors for these cancers. The probability that these compounds will induce cancer in a given individual will depend on that person's ability to metabolically activate or detoxify them. Chronic production of DNA damage by these metabolically activated carcinogens is consistent with current concepts of carcinogenesis in which multiple genetic changes, such as activation of oncogenes or inactivation of tumor suppressor genes, appear to be critical. Chemopreventive agents which decrease the level of DNA damage should therefore decrease the risk for cancer. Biomarkers such as carcinogen–DNA adducts, carcinogen-hemoglobin adducts, and urinary metabolites of carcinogens will indicate the amount of metabolically activated carcinogen which may damage DNA in an individual and can therefore be used as an index of risk. Selected biomarkers are discussed in this paper. These biomarkers of internal dose have great potential for application in chemoprevention trials.