Browsing by Subject "Tobacco"

Now showing 1 - 8 of 8
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    Describing changes in local short-term outcomes of youth-focused comprehensive tobacco control and their effect on smoking outcomes among cohorts of Minnesota Youth, 2000-2005.
    (2010-07) Alesci, Nina L.
    Introduction: The halting decline in national youth smoking prevalence indicates the need for comprehensive tobacco control (CTC). Social ecological theory postulates that CTC reduces smoking by altering social environments that influence long-term youth tobacco use. At the local level, CTC's short-term outcomes result from 1) policy action, such as ordinances restricting public smoking and youth access to tobacco; 2) school-based prevention, such as trained teachers offering proven curricula; and 3) community mobilization, such as voluntary home smoking restrictions and youth engagement. Few CTC studies document the effect of a cutoff in CTC funding on these outcomes; most studies can only weakly assert that this multilevel intervention causes youth smoking reductions. The Minnesota Adolescent Community Cohort (MACC) study evaluates the state's CTC 2000-2003 program, the Minnesota Youth Tobacco Prevention Initiative (MYTPI), and the effect of its sudden, major funding cut. The current study tested for 1) increases in short-term outcomes during the MYTPI and their sustainability after its shutdown; 2) decreases in youth smoking during the MYTPI and increases in youth smoking after the shutdown; and 3) a link between baseline levels of and changes in short-term outcomes to reduced youth smoking. Methods: MACC is a multilevel, population-based, observational cohort study of Minnesota youth (n=3,636) nested in geo-political units (GPUs; N=60), which signified local communities. A comparison group of youth (n=605) came from six Midwest states that had not dedicated major tobacco control funding. Annual ordinance, youth access enforcement, and school administrator surveys; and a twice-annual youth survey capture short-term outcomes in Minnesota. The youth survey also measures smoking outcomes. Data were collected from the MYTPI launch to two years post-shutdown (2000-2005). Analysis employs latent curve modeling, growth curves using structural equation modeling to parameterize the intercept and slope as latent variables. Piecewise latent curves modeled the effect of a sudden drop in tobacco control funding on short-term outcomes and youth smoking. Parallel process latent curves tested for contemporaneous change between short-term outcomes and youth smoking. Random coefficients models accounted for repeated measures and where appropriate, the multilevel nature of the data. Results: Implementation of short-term outcomes from school-based prevention and community-mobilization increased during the MYTPI; however, this growth eventually stopped or slowed after the shutdown. Some policy action outcomes increased minimally, and one outcome of policy action declined post-shutdown. Increases in smoking stage were the same between Minnesota and comparison groups, showing no period effects for the MYTPI or shutdown. However, younger cohorts, with early-teen MYTPI exposure, smoked less than older cohorts by the same age. Only youth access ordinances scores and living in homes banning smoking were negatively associated with smoking stage. Discussion: MYTPI implemented less controversial educational and community-mobilization strategies, but was not as successful with permanent policy change before its shutdown. This lack of policy action and youth focus could explain why Minnesota youth did not differ from other states with concurrent national tobacco control. The study offers some evidence supporting MYTPI interventions, but study flaws may make the influence of several of them undetectable. Study limitations include lack of/poor comparison group, secular trends, selection bias, measurement error, and analysis issues.
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    Elevated levels of 1-hydroxypyrene and NOe-Nitrosonornicotine in the urine of smokers with head and neck cancer: a matched control study
    (2014-04) Khariwala, Samir Suresh
    Background: Head and neck squamous cell carcinoma (HNSCC) is associated with tobacco use. Still, most smokers do not develop HNSCC. The mechanisms of varying susceptibility to HNSCC are poorly studied to date. Tobacco metabolite research provides insight regarding the innate metabolism and excretion of carcinogens. Methods: Smokers with HNSCC (cases) were compared to smokers without HNSCC (controls) in a matched cohort. The tobacco metabolites studied are: 1-hydroxypyrene (1-HOP), Nf-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). Results: In 33 subjects, mean 1-HOP was 1.82 pmol/mg creatinine vs 1.08 pmol/mg creatinine (p=0.004) and mean NNN was 0.10 pmol/mg creatinine vs 0.04 pmol/mg creatinine (p=0.01) in cases and controls, respectively. NNAL did not differ between groups. Conclusions: Smokers with HNSCC have elevated urinary levels of 1-HOP and total NNN compared to matched controls suggesting an increased effective exposure to these carcinogens. Tobacco constituent metabolites may be useful in understanding tobacco-related carcinogenesis in HNSCC.
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    Metabolism of nicotine and the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK): genetic and phenotypic variation.
    (2009-11) Berg, Jeannette Zinggeler
    Nicotine is the addictive agent in tobacco and differences in nicotine metabolism may affect tobacco use, and consequently exposure to tobacco carcinogens. A lung procarcinogen in tobacco is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its carcinogenic effect is dependent on metabolic activation and is counter-balanced by metabolic detoxification. Nicotine and NNK are structurally related and both are metabolized by cytochrome P450 (P450), UDP-glucuronosyltransferase (UGT), and flavin-monoxygenase (FMO) enzymes. The goal of this thesis research was to explore variation in nicotine metabolism in vivo and to probe specific enzyme-catalyzed reactions of NNK in vitro. Low nicotine and cotinine glucuronidation were observed among African Americans compared to Europeans, and among individuals with a variant UGT2B10 genotype. In a controlled dose study of ethnic differences in nicotine metabolism (n= 93 smokers), African Americans excreted 30-40 % less nicotine and cotinine as their glucuronide conjugates than European Americans. This difference in glucuronidation explained the higher free cotinine concentrations observed in African Americans compared to European Americans. The most efficient in vitro catalyst of nicotine and cotinine glucuronidation is UGT2B10. We demonstrated that UGT2B10 contributes to in vivo nicotine metabolism in a genotype-phenotype analysis of 325 smokers. Individuals who were heterozygous for the UGT2B10 Asp67Tyr allele excreted less nicotine or cotinine as their glucuronide conjugates than wild-type; the ratio of cotinine glucuronide:cotinine was decreased by 60 %, while increases in urinary and plasma cotinine and trans-3'-hydroxycotinine were observed. Strikingly, a robust biomarker of nicotine intake, nicotine equivalents, were lower among Asp67Tyr heterozygotes compared to individuals without this allele; 58.2 nmol/ml (95 % CI, 48.9 - 68.2) versus 69.2 nmol/ml (95 % CI, 64.3 - 74.5). Individuals with low activity UGT2B10 may smoke less intensely, as reported for individuals with CYP2A6 polymorphisms that cause decreased nicotine C-oxidation. In contrast to nicotine, NNK is a carcinogen. It is metabolized to reactive intermediates that can form DNA and protein adducts, or it is detoxified by glucuronidation. P450 2A13 is the most efficient catalyst of NNK oxidation. We explored the effect of an active site mutant, Asn297Ala, on enzyme function and found that loss of hydrogen bonding to substrate in the active site affected substrate orientation and product formation. The orphan P450 2A7 was considered as a potential catalyst for NNK oxidation, but expression of wild-type or two naturally-occurring variants failed to yield protein with a P450 spectra and no appreciable activity towards P450 2A substrates was observed. Preliminary experiments were conducted to search for the glucuronide conjugate formed from the unstable oxidation product alpha-hydroxymethyl NNK, which has not been identified in any human system. The extent to which variation in metabolism mediates smoking behavior and cancer risk warrants consideration. The enzymes involved are potential drug targets for smoking cessation pharmacotherapy and cancer chemoprevention.
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    Minutes: Senate Committee on Student Affairs: Febuary 17, 1999
    (1999-02-17) University of Minnesota: Senate Committee on Student Affairs
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    Records-based Childhood Cancer Research Applications and Methods
    (2023-08) Domingues, Allison
    Due to the rarity of childhood cancer, researchers often rely on methods such as registry linkage studies in order to gather sufficient sample size for analysis. These methods have been successfully used to establish associations between childhood cancer risk and birth certificate reported variables in the past. However, these methods have limitations. For example, variables such as maternal smoking may be misreported on birth records. Additionally, missing data, especially missing paternal data, is a concern. In manuscript 1, we investigated the association between maternal smoking and childhood cancer risk by pooling several existing registry linkage studies. We also applied a probabilistic bias adjustment in order to address misclassified smoking status. After adjustment, only other gliomas and other and unspecified malignant tumors had evidence of an association with maternal smoking. This finding falls in line with previous studies that have largely reported null associations, and greatly strengthens this finding through a strong study design and the use of probabilistic bias adjustment. In manuscript 2, we compared the performance of three different methods for handling the occurrence of impossible values (such as negative 2x2 table cell counts) in probabilistic bias analysis using simulation methods. We found that even in cases of a moderate probability of impossible values, all three methods—the removal of impossible iterations, the selection of a new parameter distribution, and Bayesian methods—performed similarly. However, further analysis is needed. In manuscript 3 we investigated the use of genotype data from newborn dried blood spots and other birth certificate derived variables in the imputation of missing paternal race/ethnicity. This analysis provides evidence that random forest methods can reliably impute missing paternal race/ethnicity using a child’s global ancestry and maternal race/ethnicity as predictors. We also demonstrated how these methods better situate prediction in specific populations when compared to ancestry cut-off-based methods.
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    Smoking Cessation
    (2011-08-03) Coughlin, Ohmar
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    Socioeconomic status and tobacco use behavior in adolescence.
    (2010-08) Mathur, Charu
    INTRODUCTION: Despite the known health problems associated with tobacco use, adolescents continue to initiate and develop regular patterns of tobacco use. Globally adult tobacco consumption is strongly associated with poverty, with those in lower socioeconomic classes using tobacco at higher rates. The association between socioeconomoic status (SES) and tobacco use for youth, however, is much less clear. Understanding the role of SES in initiation and progression of tobacco use among adolescents can improve our ability to design effective interventions targeting adolescent tobacco use behavior. The aim of this dissertation was to examine the impact of SES on tobacco use in youth across different countries, presented in three related manuscripts. METHODS: In the first manuscript, the effect of both individual and community- level SES on smoking outcome was evaluated in the Minnesota Adolescent Community Cohort (MACC) study, a population-based, observational cohort study designed to assess the effects of tobacco control policies and programs on adolescent smoking. Additionally, the cross-level interaction of these two SES measures was examined. The analyses employed a multiple group, multiple cohort growth model. In the second manuscript latent class analysis (LCA) was used to establish classes of tobacco acquisition in the Mobilizing Youth for Tobacco Related Initiatives (MYTRI) study, a large-scale intervention trial in two large cities in India. The third manuscript explored change in tobacco use over time and the moderating effect of SES on change, also in the MYTRI study. Additionally, the distribution of related psychosocial risk factors across schools type was also evaluated. RESULTS: In paper 1, individual-level SES was associated with smoking (low SES was associated with higher adolescent smoking), but community-level SES was not. However, the results for cross-level interaction show that community socioeconomic context affected smoking behavior differentially depending on individual socioeconomic position (i.e., community-level SES had stronger effects on low individual-SES adolescents than on high individual-level SES youth). The results from paper 2 suggest that a 3-latent class and a 4-latent class model were most appropriate for this adolescent population, in private and government schools, respectively. Although, the number of latent classes was the same at both time points, the meaning of these classes differed over time. Finally, in paper 3, the findings about the relationship between SES and tobacco were inconsistent, suggesting a potential change over time in the association of SES and tobacco use. At baseline, low SES was associated with higher prevalence of tobacco use but the relation between SES and tobacco use reversed two years later. These findings were mirrored in the distribution of related psychosocial risk factors. CONCLUSIONS: This dissertation served to examine the relationship between SES and adolescent tobacco use in two different countries/settings. Reducing tobacco initiation and progression in low SES youth that are disproportionately affected is dependent upon effective and sustainable interventions as well as a more comprehensive understanding of the role SES in influencing an adolescent's tobacco use behavior.
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