Abstract
DNA adducts are believed to play a central role in the induction of cancer in cigarette smokers and are proposed as being potential biomarkers of cancer risk. We have summarized research conducted since 2012 on DNA adduct formation in smokers. A variety of DNA adducts derived from various classes of carcinogens, including aromatic amines, polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, alkylating agents, aldehydes, volatile carcinogens, as well as oxidative damage have been reported. The results are discussed with particular attention to the analytical methods used in those studies. Mass spectrometry-based methods that have higher selectivity and specificity compared to 32P-postlabeling or immunochemical approaches are preferred. Multiple DNA adducts specific to tobacco constituents have also been characterized for the first time in vitro or detected in vivo since 2012, and descriptions of those adducts are included. We also discuss common issues related to measuring DNA adducts in humans, including the development and validation of analytical methods and prevention of artifact formation.
Highlights
Cigarette smoking causes multiple types of cancers
While 90% of all lung cancer-related deaths in the U.S are attributable to cigarette smoking, only 24% of male smokers and 11% of female smokers may die from lung cancer over their lifetime, assuming that there is no competing cause of death [4,5]
We have demonstrated the association of certain urinary tobacco smoke biomarkers with lung cancer risk, independent of smoking intensity and duration
Summary
Cigarette smoking causes multiple types of cancers. Despite the advent of advanced cancer genomics and impressive targeted therapies, there were still an estimated 9.6 million cancer deaths worldwide in 2018 with 22% of those deaths being caused by cigarette smoking [1]. Low activity forms of cytochrome P450 2A6, the major nicotine metabolizing enzyme, have been related to decreased lung cancer risk in cigarette smokers [9]. The ultimate goal is to quantify these tobacco smoke-related DNA adducts in human biological samples and to incorporate the results into epidemiologic studies to evaluate and validate their role in cancer risk prediction (Figure 1). While this challenging goal has yet to be reached, constantly improving methods for DNA adduct quantitation, as discussed here, provide at least a potential path.
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