High level of tobacco carcinogen-derived DNA damage in oral cells is an independent predictor of oral/head and neck cancer risk in smokers

Exposure to tobacco-specific nitrosamines (TSNA) and polycyclic aromatic hydrocarbons (PAH) is recognized to play an important role in the development of oral/head and neck squamous cell cancer (HNSCC).  We recently reported higher levels of TSNA-associated DNA adducts in the oral cells of smokers with HNSCC as compared to cancer-free smokers.  In this study we further investigated the tobacco constituent exposures in the same smokers to better understand the potential causes for the elevated oral DNA damage in smokers with HNSCC.  Subjects included cigarette smokers with HNSCC (Cases, n=30) and cancer-free smokers  (Controls, n=35). At recruitment, tobacco/alcohol use questionnaires were completed, urine and oral cell samples were obtained. Analysis of urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and N'-Nitrosonornicotine (NNN) (TSNA biomarkers), 1-hydroxypyrene (1-HOP, a PAH), cotinine, 3'-hydroxycotinine and the nicotine metabolite ratio (NMR) were performed.  Cases and controls differed in mean age, male preponderance and frequency of alcohol consumption (but not total alcoholic drinks).  Univariate analysis revealed similar levels of NNN, 1-HOP and cotinine between groups but, as reported previously, significantly higher DNA adduct formation in the cases.  Multiple regression adjusting for potential confounders showed persistent significant difference in DNA adduct levels between cases and controls (ratio of geometric means: 20.0 (95% CI=2.7-148.6)).  Our cohort of smokers with HNSCC demonstrates higher levels of TSNA-derived oral DNA damage in the setting of similar exposure to nicotine and tobacco carcinogens.  Among smokers, DNA adduct formation may act as a predictor of eventual development of HNSCC that is independent of carcinogen exposure indicators.

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