) The overall aim of this TTURC is to identify familial, early childhood and lifetime psychiatric factors that determine: trajectories of progression from smoking initiation to dependence; lifetime smoking patterns; the natural course of cessation; and response to treatment. Our proposed program of research combines a treatment/prevention imperative, a genetic epidemiologic approach, and a lifespan developmental perspective, sharing common scientific resources, to advance research on human nicotine dependence from basic mechanisms to applied interventions. We will use a synergistic combination of a community-based sample, prospective design, and a multigenerational family study to examine the major pathways to nicotine dependence, and to develop and validate a lifespan taxonomy of tobacco use and nicotine dependence phenotypes. The major goal is to identify modifiable risk factors that can serve as targets for prevention and that may be harnessed to enhance smoking prevention and cessation treatment success. We recognize that many such modifiable risk factors may act in concert with or against a substrate of genetic risks, and reason that a combined environmental and genetic/familial strategy is required both to clearly identify salient environmental agents and to prepare for studies of susceptibility genes. To this end, we propose to: l) To integrate multiple disciplinary perspectives and research methods front basic science to applications including (a) longitudinal natural history research (developmental epidemiology); (b) familial aggregation methods (genetic epidemiology); (c) human laboratory studies; and (d) intervention trials; (2) To adopt this lifespan and transgenerational genetic epidemiological approach to help understand risk factors for and causal pathways of: (a) progression of nicotine dependence among youth; (b) patterns of adult smoking; (c) the natural course of smoking cessation; and (d) response to treatment; (3) To document the potential utility and cost-effectiveness of a sustained """"""""care management"""""""" approach to treating smokers that addresses smokers' risk profiles (from relatively uncomplicated to multiple comorbidities) with a range of treatment options that vary along dimensions of intensity and modality of intervention; (4) To collect and preserve DNA with the anticipation that, after refining phenotypic definitions, characterizing candidate genes (in other samples), and identifying the most heritable forms of smoking behavior, we may inform and conduct an efficient and productive strategy to identify susceptibility genes for nicotine dependence.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA084719-03
Application #
6377737
Study Section
Special Emphasis Panel (ZCA1-SRRB-Y (O2))
Program Officer
Etz, Kathleen
Project Start
1999-09-30
Project End
2004-09-29
Budget Start
2001-09-30
Budget End
2002-09-29
Support Year
3
Fiscal Year
2001
Total Cost
$2,358,734
Indirect Cost
Name
Miriam Hospital
Department
Type
DUNS #
039318308
City
Providence
State
RI
Country
United States
Zip Code
02906
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