GENE-NEIGHBORHOOD INTERACTION IN ADOLESCENT AND YOUNG ADULT SMOKING

描述（由申请人提供）：吸烟是癌症死亡的主要可预防原因，占美国所有癌症死亡人数的30%以上。尽管有关于吸烟对健康不良影响的警告，但美国人，尤其是青少年和年轻人的吸烟率仍然很高。大多数成年吸烟者在18岁之前开始吸烟，并在青年时期形成烟草依赖。青少年和年轻人吸烟仍然是最具挑战性的公共卫生问题之一。吸烟行为具有高度遗传性，也受到环境的影响。虽然吸烟的遗传和其他个人危险因素已经很好地确立，但只有少数研究调查了社区对青少年和年轻人吸烟的影响。虽然基因-环境对吸烟的相互作用已被广泛评估，但环境通常集中在个人或家庭层面的因素上。没有研究调查不良邻里环境和遗传风险因素对吸烟的相互作用。在多层次的框架下，研究吸烟行为的总体地理差异、吸烟遗传影响的地理异质性以及邻里不利因素对吸烟的影响的改变，将有助于改善烟草控制和戒烟干预。基因改变结合邻里剥夺可以通过细分风险水平（风险分层）和改进预防选择来优先考虑干预的目标人群。因此,使用

DESCRIPTION (provided by applicant): Cigarette smoking is the leading preventable cause of cancer mortality and accounts for more than 30% of all cancer deaths in the United States. Despite warnings about its adverse health effects, the prevalence of smoking is still high among US persons, especially among adolescents and young adults. Most adult smokers initiated smoking before age 18 years and developed tobacco dependence during their young adulthood. Adolescent and young adult smoking remains one of the most challenging public health issues. Smoking behaviors are highly-heritable and also influenced by environments. Although genetic and other individual risk factors of smoking have been well established, only few studies examined neighborhood effects on adolescent and young adult smoking. While gene-environment interactions on smoking have been widely evaluated, the environment has been focused typically on individual- or family-level factors. No studies have investigated the interaction between adverse neighborhood conditions and genetic risk factors on smoking. In a multilevel framework, the examination of overall geographic variation in smoking behaviors, geographic heterogeneity of genetic influences on smoking, and effect modification of neighborhood disadvantages on smoking will be able to significantly facilitate improving tobacco control and the intervention in smoking cessation. Genetic alterations combined with neighborhood deprivation could prioritize the target population of the intervention through subdividing the risk levels (risk stratification) and refining prevention choices. Therefore, using the Missouri Adolescent Female Twin Study (MOAFTS) data, we will explore the hypothesis that neighborhood environments modify the influence of genetic predispositions on cigarette smoking among adolescents and young adults. Three specific aims will be addressed: (1) Quantify the small-area geographic variation in adolescent and young adult smoking; (2) Identify neighborhood characteristics that are associated with adolescent and young adult smoking; and (3) Prospectively assess if genetic influences on smoking outcomes vary across distinct neighborhood environments. We will develop neighborhood measures based on area-level data and link them to the MOAFTS data after gecoding the residential addresses of study subjects to prospectively assess the independent and interactive effects of neighborhood environment with genetic predispositions on adolescent and young adult smoking. This award will allow the applicant to gain advanced skills in research methodology and behavioral genetics of smoking behaviors. The findings from the proposed study will provide important support to further investigate gene-neighborhood interplay on smoking through the R01 mechanism. The training and research experience obtained during this award, in combination with the excellence and expertise of his mentoring team (Drs. Mario Schootman, Andrew Heath, Pamela Madden, and Graham Colditz), will promote applicant's transition to an independent academic researcher in smoking prevention and tobacco control.