Folate Metabolism & Methylation in Lung Cancer

叶酸代谢

• 批准号: 7880159
• 负责人: Kristina Garnand Flores
• 金额: $ 13.69万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-20 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7880159
• 关键词: Advisory Committees; American; Area; Biological Assay; Blood; Case Study; Chest; DNA; Data; Databases; Development; Development Plans; Environment; Environmental Risk Factor; Epidemiologic Studies; Epidemiology; Folate; Food; Fostering; Frequencies; Gene Expression; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Goals; Hand; Intake; International; Laboratories; MGMT gene; Malignant neoplasm of lung; Medical center; Mentorship; Metabolism; Methylation; Molecular Biology; Molecular Epidemiology; New Mexico; PAX5 gene; Pattern; Prevalence; Public Health; Questionnaires; Research; Research Institute; Research Training; Resources; Risk; Role; Smoke; Smoker; Smoking; Societies; Spirometry; Sputum; Testing; Training; Universities; Veterans; base; career; career development; case control; cohort; folic acid metabolism; high risk; innovation; lung cancer prevention; member; population based; programs; promoter; respiratory; skills

DESCRIPTION (provided by applicant): The goals of this career development plan are to develop expertise in the area of molecular epidemiology and initiate an independent research career focused on population based study of genetic susceptibility to lung cancer. This plan includes didactic coursework in epidemiology through the University of New Mexico's Master's in Public Health program, hands on training in expert epidemiology and molecular biology laboratories, mentorship from an advisory committee, and a molecular epidemiology based research agenda. The goal of the proposed research is to examine the association of folate gene polymorphisms, dietary folate intake, and folate gene expression changes with lung cancer predictive promoter methylation patterns. The following 8 genes are analyzed for promoter methylation in the sputum of smokers: p16, MGMT, RASSF1A, DAPK, GATA5 and GATA4, PAX5( and PAX5(. Smokers that have 3 or more methylated gene promoters from a panel of these eight genes have a 6.5 fold greater risk to develop lung cancer compared to smokers with 0 methylated gene promoters. Thus, smokers with 3 or more methylated gene promoters assayed from this panel are defined as cases for this study and smokers with 0 methylated genes are defined as controls. Cases and controls come from high risk smoking cohorts from the Lovelace Respiratory Research Institute and the Albuquerque Veterans Affairs Medical Center in Albuquerque, New Mexico. Extensive data are collected for these cohorts including sputum, blood, spirometry, Harvard Food Frequency questionnaire data, and American Thoracic Society respiratory questionnaire data. The proposed training and research agenda in this proposal will draw upon and strengthen the candidate's skills in molecular biology and further develop her skills in population based research and epidemiology. The research agenda of this plan will contribute to a greater understanding of the genetic and environmental factors involved in the development of lung cancer and foster further research questions about the role of environment and genetic susceptibility for lung cancer prevention and treatment.

描述（由申请人提供）：该职业发展计划的目标是在分子流行病学领域发展专业知识，并启动独立的研究职业，该研究专注于基于人群的遗传易感性研究肺癌的研究。该计划包括通过新墨西哥大学的公共卫生硕士课程，专家流行病学和分子生物学实验室培训，咨询委员会的指导以及基于分子流行病学的研究议程的教学培训，包括在流行病学方面的教学课程。拟议的研究的目的是检查叶酸基因多态性，饮食叶酸摄入和叶酸基因表达随肺癌预测启动子甲基化模式的变化。在吸烟者的痰液中分析了以下8个基因的启动子甲基化：p16，mgmt，rassf1a，dapk，gata5和gata4和gata4，pax5（和pax5（和pax5（吸烟者具有3.5基因的甲基化基因促进者的3.5倍数促进的甲基化基因与吸烟者相比，甲基化的甲基化基因相比，甲基化的甲基基因较大的甲基甲基化的甲基化剂均与llimes相比，甲基化的甲基化甲基化的甲基化含量为lime，甲基化的3.5倍数。 or more methylated gene promoters assayed from this panel are defined as cases for this study and smokers with 0 methylated genes are defined as controls. Cases and controls come from high risk smoking cohorts from the Lovelace Respiratory Research Institute and the Albuquerque Veterans Affairs Medical Center in Albuquerque, New Mexico. Extensive data are collected for these cohorts including sputum, blood, spirometry, Harvard Food Frequency questionnaire数据和美国胸腔学会呼吸问卷数据。 该提案中提出的培训和研究议程将借鉴并增强候选人在分子生物学方面的技能，并进一步发展她在基于人群的研究和流行病学方面的技能。该计划的研究议程将有助于对肺癌发展所涉及的遗传和环境因素有助于进一步研究有关环境作用以及预防肺癌预防和治疗的遗传易感性的问题。