Abstract 3223: Metabolomic study reveals smokers’ characteristic profile.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Given recent FDA legislation to mandate cigarette performance standards and evaluate health claims for modified tobacco products, and separately the fact that most persons with lung cancer are former smokers, biomarkers of lung cancer risk are needed. Yet, today there are only a few biomarkers of exposure and none that are validated for lung cancer risk. This study identified putative biomarkers of exposure and harm through metabolomics, a powerful method to identify numerous metabolites and profiles. It utilized a previously conducted epidemiological study of well-characterized smokers. Using UPLC-QTOF-MS, we analyzed global metabolomic profiles of 160 smokers’ plasma totaling 613 repeated samples, and evaluated whether gender, race, number of cigarettes per day, nicotine metabolism, and type of cigarette is associated with smokers’ global metabolome. These subjects completed an extensive interview and smoked two cigarettes in a smoking laboratory. Blood and CO measurements were collected before and after each cigarette. Using subset analysis for the effect of gender on smokers’ metabolome, we were able to identify putative metabolites that are mostly steroid hormones or cholesterol derivatives, signifying the importance of sex-specific differences in metabolism. There was also significant discrimination in the metabolome of heavy and light smokers, of African-American and Caucasian smokers, and of menthol and non-menthol cigarette smokers. We also performed a paired analysis on menthol versus non-menthol smokers matched by race, gender, metabolizer status, and smoking status. Our result showed not only a significant discrimination between metabolomes of these two cigarette types, but also discriminated a cigarette brand with the lowest nicotine yield from the one with the highest yield. Putative metabolites were identified including several related to carcinogenesis and the inhibition of actin cytoskeleton activation. Further validation is needed to identify and characterize those metabolites. In summary, we have shown that the potential biomarkers identified in this study are strongly related to other well established lung cancer risk factors including gender, race, and tobacco exposure variables, and therefore may be useful in cohort studies of persons at high risk for lung cancer. Citation Format: Ping-Ching Hsu, Bin Zhou, Habtom W. Ressom, Amrita Cheema, Christopher A. Loffredo, Wallace Pickworth, Peter G. Shields. Metabolomic study reveals smokers’ characteristic profile. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3223. doi:10.1158/1538-7445.AM2013-3223