DNA repair, Cell cycle Checkpoints and Apoptosis and Bladder Cancer Risk

DNA 修复、细胞周期检查点和细胞凋亡以及膀胱癌风险

基本信息

批准号：
7848344
负责人：
Jie Lin
金额：
$ 13.49万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7848344
关键词：
Address Age Algorithms Alleles American Apoptosis Apoptotic Area Arts Bioinformatics Biological Biological Assay Biological Markers Bladder Cancer Biology Cancer Center Carcinogen Metabolism Carcinogens Case Study Case-Control Studies Caucasians Caucasoid Race Cell Cycle Checkpoint Cell Cycle Regulation Cell physiology Cells Clinic Clinical Clinical Oncology Complement Complex Correlation Studies DNA DNA Repair Data Development Development Plans Dietary Practices Disease Doctor of Medicine Enrollment Environment Environmental Exposure Environmental Risk Factor Epidemiologist Epidemiology Erythrocytes Ethnic Origin Exposure to Frequencies Funding Gender Gene Order Genes Genetic Genetic Markers Genetic Polymorphism Genetic Predisposition to Disease Genetic Variation Genomics Genotype Goals Haplotypes Human Genetics Individual Journal of the National Cancer Institute Journals Knowledge Length Lymphocyte Machine Learning Malignant Neoplasms Malignant neoplasm of urinary bladder Medical Medicine Mentors Methods Modeling Molecular Molecular Epidemiology Mutagens Newly Diagnosed Nutritional Occupational Outcome Paper Parents Pathway interactions Penetrance Phenotype Physicians Plasma Population Predictive Value Predisposition Publishing Recruitment Activity Research Personnel Research Project Grants Research Proposals Resources Risk Assessment Sampling Smoker Specimen Statistical Methods Suspension substance Suspensions Tobacco Tobacco smoke Training Variant anticancer research base cancer risk carcinogenesis career development case control college coping gene environment interaction gene interaction genotyping technology high risk intervention program medical specialties meetings men new technology novel parent grant sex skills statistics telomere tool

项目摘要

DESCRIPTION (provided by applicant): My long-term goal is to become an independent molecular epidemiologist with in-depth training in genetics and advanced statistical methods in order to be able to analyze high throughput gene variant data to explore gene-gene and gene-environment interactions in cancer susceptibility. My career development plan include didatic courses/seminars, meetings with mentors in the areas of human genetics, cancer biology and advanced statistical methods. My research proposal will focus on genetic susceptibility of bladder cancer (BC). I propose to capitalize on availability of epidemiologic and genetic marker data from an on-going case-control study, "Markers of Genetic Susceptibility to Bladder Cancer"(R01 CA74880,PI:Xifeng. Wu). The parent study currently include over 2,500,mostly Caucasian, BC cases and controls, matched on sex, age and ethnicity. My goal is to identify novel loci that confer bladder cancer susceptibility using state-of-the-art genotyping technology and novel statistical and bioinformatics tools. The Specific Aims are: 1) To enhance my knowledge and skills in genetics and statistics to identify novel genetic loci as susceptibility markers of BC by extending the original45 potential functional SNPs to include additional 2112 tagging SNPs in genes in the DNA repair, cell cycle control and apoptotic pathways in 800 Caucasian cases and 800 Caucasian controls using the Illumina Golden Gate Assay; 2) To assess haplotypes and diplotypes as markers of susceptibility; 3) To use bioinformatics tools to assess functional significance of SNPs in the DNA repair, cell cycle control and apoptotic pathways and to correlate genotype data of DNA repair and cell cycle control with functional data derived from phenotypic assays. The secondary aim is to apply hierarchical models to refine risk assessment and to apply novel machine-learning tools to explore any gene-environment and gene-gene interactions influencing BC risk. My project complements the parent grant in that it: 1) adds tagging SNPs to potential functional SNPs addressed in the parent grant; 2) adds haplotype analyses; 3) proposes novel statistical and bioinformatics approaches. RELEVANCE: Bladder cancer is a tobacco-related cancer which is the fourth most common cancer in men in U.S. The fact that only a fraction of smokers develop bladder cancer indicating genetic susceptibility to the disease. This study will identify novel genetic markers may be useful as biomarkers to identify high-risk populations that could then be targeted for intervention programs.

描述（由申请人提供）：我的长期目标是成为一名独立的分子流行病学家，接受过深入的遗传学培训和先进的统计方法，以便能够分析高通量基因变异数据，探索基因-基因和基因-基因之间的关系。环境相互作用对癌症易感性的影响。我的职业发展计划包括教学课程/研讨会、与人类遗传学、癌症生物学和高级统计方法领域的导师会面。我的研究计划将集中于膀胱癌（BC）的遗传易感性。我建议利用正在进行的病例对照研究“膀胱癌遗传易感性标记”（R01 CA74880，PI：Xifeng. Wu）中提供的流行病学和遗传标记数据。母公司研究目前包括超过 2,500 名不列颠哥伦比亚省病例和对照，其中大部分是白种人，并在性别、年龄和种族上进行匹配。我的目标是利用最先进的基因分型技术以及新颖的统计和生物信息学工具来识别赋予膀胱癌易感性的新位点。具体目标是： 1) 增强我在遗传学和统计学方面的知识和技能，通过扩展原来的 45 个潜在功能性 SNP，将 DNA 修复、细胞周期控制等基因中的额外 2112 个标记 SNP 纳入其中，从而识别新的遗传位点作为 BC 的易感性标记。使用 Illumina Golden Gate 检测对 800 个白人病例和 800 个白人对照进行细胞凋亡途径； 2) 评估单倍型和双倍型作为易感性标记； 3) 使用生物信息学工具评估 SNP 在 DNA 修复、细胞周期控制和凋亡途径中的功能意义，并将 DNA 修复和细胞周期控制的基因型数据与表型测定的功能数据相关联。第二个目标是应用分层模型来完善风险评估，并应用新颖的机器学习工具来探索影响乳腺癌风险的任何基因-环境和基因-基因相互作用。我的项目对父资助的补充在于：1) 将标记 SNP 添加到父资助中涉及的潜在功能性 SNP 中； 2) 增加单倍型分析； 3）提出新的统计和生物信息学方法。相关性：膀胱癌是一种与烟草相关的癌症，是美国男性第四大常见癌症。事实上，只有一小部分吸烟者患有膀胱癌，这表明对该疾病具有遗传易感性。这项研究将确定新的遗传标记，这些标记可能可用作生物标记来识别高危人群，然后将其作为干预计划的目标。