Abstract 4701: DNA-adducts levels and chromosomal aberrations in relation to smoking history and topography in smokers

Abstract

Abstract Introduction: Tobacco smoking is the major cause of morbidity and mortality in developed countries. Important determinants of tobacco carcinogen exposure include the smoking history and smoking topography. Tobacco carcinogens-induced DNA adducts and chromosomal aberrations have been associated with cancer development. It is unknown if the choice of cigarettes and smoking topography lead to differences in carcinogen-DNA adduct levels and chromosomal aberrations. Methods: We studied 207 population-based smokers (97 Caucasians and 110 African Americans). The subjects smoked two cigarettes, one hour apart, and the smoking topography was measured. We assessed three parameters of smoke exposure (serum cotinine, nicotine boost and carbon monoxide boost) in order to collect corroborative evidence that reflect different types of exposure. Carcinogen-DNA adducts and chromosomal aberrations in lymphocytes were determined by using the 32P-postlabeling analysis and standard cytogenetic method, respectively. Results: The chance of having high level of DNA-adducts was significantly higher in males than females (OR: 1.9; 95%CI: 1.09-3.31). Weakly associations of the DNA-adducts were observed with age and race (higher in older people and African-Americans smokers) (OR: 1.7; 95%CI: 0.97-2.90; OR: 1.5; 95%CI: 0.87-2.60). DNA-adducts were significantly associated with the baseline and post cigarette CO level for the first (p-value=0.001; 0.007 respectively) and second cigarette (p-value=<0.001; 0.001 respectively), with the total number of puffs for the second cigarette (p-value=0.04) and with the cumulative topography (p-value=0.03). Marginal associations were observed for the changes in CO2 pre and post cigarettes (p-value=0.08), the average inter-puff interval and the total puff volume for the second cigarette (p-value=0.06; 0.07 respectively). The changes in CO2 pre and post first and second cigarette were significantly associated with the mean number of chromosomal aberrations per cell (p-value=0.05; 0.01 respectively). Conclusion: In this study we observed potentially important associations of smoking topography with both DNA adduct levels and chromosomal aberrations. Larger study sets will be necessary to clarify the magnitude of these associations and to account for baseline differences related to gender, age, and race. Such an approach could provide useful information for understanding differential susceptibility to lung cancer among smokers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4701.