This perspective considers the use of oral cell DNA adducts, together with exposure and genetic information, to potentially identify those cigarette smokers at highest risk for lung cancer, so that appropriate preventive measures could be initiated at a relatively young age before too much damage has been done. There are now well established and validated analytical methods for the quantitation of urinary and serum metabolites of tobacco smoke toxicants and carcinogens. These metabolites provide a profile of exposure and in some cases lung cancer risk, but they do not yield information on the critical DNA damage parameter that leads to mutations in cancer growth control genes such as KRAS and TP53. Studies demonstrate a correlation between changes in the oral cavity and lung in cigarette smokers, due to the field effect of tobacco smoke. Oral cell DNA is readily obtained in contrast to DNA samples from the lung. Studies in which oral cell DNA and salivary DNA have been analyzed for specific DNA adducts are reviewed; some of the adducts identified have also been previously reported in lung DNA from smokers. The multiple challenges of developing a panel of oral cell DNA adducts that could be routinely quantified by mass spectrometry are discussed.
Bibliographical noteFunding Information:
Stephen S. Hecht: 0000-0001-7228-1356 Funding This research is supported by grants CA-81301 and CA-138338 from the U.S. National Cancer Institute. Notes The author declares no competing financial interest. Biography Stephen S. Hecht received his B.S. in chemistry from Duke University and his Ph.D. in organic chemistry from the Massachusetts Institute of Technology, where he also did postdoctoral research in mass spectrometry. Prior to moving to the University of Minnesota in 1996, he conducted research at the American Health Foundation in Valhalla, NY for 23 years, and was Director of Research from 1987−1996. At the University of Minnesota, he served as Head of the Carcinogenesis and Chemoprevention Program of the Masonic Cancer Center from 1997−2014 and is a current member of the Medicinal Chemistry and Pharmacology graduate programs.