The Association of a Tobacco-Specific Biomarker and Cigarette Consumption and Its Dependence on Host Characteristics

Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Rockville, MD 20852, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 10/2007; 16(9):1852-7. DOI: 10.1158/1055-9965.EPI-07-0018
Source: PubMed


The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent carcinogen, which can be characterized by urinary concentrations of the metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNAL) and its glucuronide. Using baseline data in current smokers from four clinical trials, we examine the associations of urinary cotinine with CPD and of total NNAL with cotinine and the modification of these associations by several host factors. There was a linear relationship between ln(cotinine) and ln(CPD) within categories of the Fagerstrom Test of Nicotine Dependence and of age. The increasing trend was significantly smaller for subjects with high and very high nicotine addiction and for older subjects and larger in females than males. The regression of ln(total NNAL/cotinine) on ln(cotinine) declined linearly, suggesting reduced NNK uptake per unit cotinine with increasing cotinine. The decline in trend was greater in subjects with increased CPD, with greater nicotine addiction, and at older ages and was smaller in females, although gender differences were small. Variations in the ratio with host characteristics were generally similar to a recent epidemiologic analysis of effect modification of the association between lung cancer and cigarette smoking.

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    • "More directly, nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-buta- none (NNK) is a tobacco-specific carcinogen. Among smokers, ratios of urinary NNK metabolites to urinary cotinine declined with increasing cotinine, indicating reduced NNK uptake per unit cotinine with increasing cotinine (Lubin et al, 2007b "
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    • "uivalents were reduced by 70% , 80% , and 44% in the previous confinement study compared to 50% , 48% and 7% , respectively , in this study . This is noteworthy since a reduction of CC consumption and / or CC tar yields in many studies does not necessarily result in a reduction in biomarkers of expo - sure to HPHC ( Hatsukami et al . , 2006a , b ; Lubin et al . , 2007 ; Joseph et al . , 2008 ) . While in short - term confinement studies , it is possible to obtain accurate data about the types and quantities of cigarettes smoked , longer - term ambulatory studies are reliant on accurate self - report - ing . It would be beneficial to develop and validate a biomarker for detection of dual use of a test"
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    ABSTRACT: This randomized, open-label, ambulatory, controlled clinical study investigated biomarkers associated with cardiovascular risk and biomarkers of exposure to 10 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke in 316 male and female Polish smokers. Subjects were randomized to continue smoking conventional cigarettes (CC; N=79) or switch to smoking the Electrically Heated Cigarette Smoking System series-K cigarette (EHCSS-K6; N=237). Biomarker assessments were performed at several time points during the study at baseline and during the 1-month investigational period. The primary biomarkers were high-sensitivity C-reactive protein and white blood cell counts. No statistically significant differences in the two primary biomarkers were found between the study groups at the end of the study. End-of-study comparisons of secondary biomarkers between study groups indicated an increase in high-density lipoprotein cholesterol, and reductions in red blood cell count, hemoglobin, and hematocrit levels in the EHCSS-K6 group. All biomarkers of exposure to cigarette smoke HPHC were decreased in the EHCSS-K6 group, despite an increase in cigarette consumption, compared to the CC group. There were no apparent differences in any of the safety assessment parameters between the groups, and the overall incidence of study-related adverse events was low.
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    • "In the USA, the National Health and Nutrition Examination Survey (NHANES) provides population-based national estimates of smoking prevalence using both standard questionnaire and serum cotinine concentration [39]. Most previous studies were based on selective samples from existing observational studies [6,8,18,25,37] or smoking cessation trials [21,22,29]. Other factors affecting validity also need to be considered. "
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    ABSTRACT: Characterizing and comparing the determinant of cotinine concentrations in different populations should facilitate a better understanding of smoking patterns and addiction. This study describes and characterizes determinants of salivary cotinine concentration in a sample of Spanish adult daily smoker men and women. A cross-sectional study was carried out between March 2004 and December 2005 in a representative sample of 1245 people from the general population of Barcelona, Spain. A standard questionnaire was used to gather information on active tobacco smoking and passive exposure, and a saliva specimen was obtained to determine salivary cotinine concentration. Two hundred and eleven adult smokers (>16 years old) with complete data were included in the analysis. Determinants of cotinine concentrations were assessed using linear regression models. Salivary cotinine concentration was associated with the reported number of cigarettes smoked in the previous 24 hours (R2 = 0.339; p < 0.05). The inclusion of a quadratic component for number of cigarettes smoked in the regression analyses resulted in an improvement of the fit (R2 = 0.386; p < 0.05). Cotinine concentration differed significantly by sex, with men having higher levels. This study shows that salivary cotinine concentration is significantly associated with the number of cigarettes smoked and sex, but not with other smoking-related variables.
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