Studies conclude that the cessation rates amongst African Americans are lower than White Americans despite the fact that this group smokes fewer cigarettes per day than White Americans (1-4). Furthermore, African Americans experience disproportionately higher rates of tobacco-related morbidity (5-7). I hypothesize that African Americans may have a more difficult time with quitting smoking because of their inability to metabolize nicotine and its metabolites efficiently. As a result, this research will attempt to determine if there is a correlation between smoking cessation rates amongst African Americans and their nicotinic metabolic profile. This research project will use LC/MS to measure the nicotinic metabolic profile of African Americans participating in smoking cessation clinics. An improved LC/MS method will be developed enhancing the sensitivity and accuracy of detection of nicotine and its major metabolites, cotinine, trans-3'-OH-cotinine, nicotine N'-oxide, 4-OH-4-(3-pyridyl)-butanoid acid, nicotine-A/-glucuronide, cotinine-A/-glucuroninde and trans- 3'-OH-cotinine-O-glucuronide, in urine samples. The improved LC/MS method will incorporate a q-TOF mass analyzer extending the sensitivity and accuracy of the developed method relative to the current LC/MS (ESIquadrupole) methods in practice to date. The project will focus on sequestering urine samples from African Americans participating in smoking cessation clinics. The samples will be analyzed and the levels of nicotine and its major metabolite, cotinine, quantified. Again, the research project will establish a metabolic profile of African Americans participating in a smoking cessation clinic and investigate whether or not there is a correlation between cessation rates and metabolic profile. Studies also conclude that exposure to environmental tobacco smoke (ETS) contributes to a majority of the cancer cases amongst non-smokers (8,9). Because of the low-levels of cancer causing tobacco metabolites in the urine sample of non-smokers, a reliable and simple extraction method is needed to measure nicotine metabolites. Current extraction methods are too cumbersome and time-consuming. Furthermore, because of the kinetics of degradation of nicotine and the time-consuming preparation times, the extraction methods can induce errors in quantitation of nicotine in urine samples. This research project will expand the studies conducted in the laboratory of Dr. Gang Chen at PSCOM, as well as focus on developing a robust, reliable method to extract nicotine and its metabolites from the urine of non-smokers. The main purpose of this component of the research project is so that the researcher can become better acquainted with the procedures and practices in place related to conducting clinical research and cancer related research.
The specific aims of this research project are as follows:
Specific Aims : 1. To develop a quantitative LC/MS method using a quadrupole time-of-flight mass spectrometer (qTOF) to detect low levels of nicotine and its major metabolites, in urine samples. 2. To apply the developed qTOF method to investigate the metabolic profile of African-Americans attempting to quit smoking. 3. To develop better extraction methods of nicotine and its metabolites from urine samples of SHS. 4. To continue existing research and technology developed by Dr. Gang Chen to measure low levels of nicotine and its metabolites in non-smokers (SHS) exposed to environmental tobacco smoke (ETS)
|Modesto, Jennifer L; Hull, Anna; Angstadt, Andrea Y et al. (2015) NNK reduction pathway gene polymorphisms and risk of lung cancer. Mol Carcinog 54 Suppl 1:E94-E102|