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

• 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
• 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

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，在遗传学和先进的统计方法方面接受过深入的培训，以便能够分析高通量基因变异数据，探索癌症易感性中的基因-基因和基因-环境相互作用。我的职业发展计划包括教学课程/研讨会，与人类遗传学，癌症生物学和先进统计方法领域的导师会面。我的研究计划将集中在膀胱癌（BC）的遗传易感性。我建议利用一项正在进行的病例对照研究“膀胱癌遗传易感性标志物”（R 01 CA 74880，PI：Xifeng）的流行病学和遗传标志物数据。Wu）.母研究目前包括超过2,500例，大多数是白人，BC病例和对照，在性别，年龄和种族上匹配。我的目标是使用最先进的基因分型技术和新的统计学和生物信息学工具来确定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，通过扩展原始的45个潜在功能SNP，在800名白人病例和800名白人对照中的DNA修复、细胞周期控制和细胞凋亡途径中的基因中纳入额外的2112个标签SNP，以识别作为BC易感性标志物的新型遗传基因座。使用Illumina Golden Gate检测; 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来自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，并应用新的机器学习工具来探索影响BC风险的任何基因-环境和基因-基因相互作用。我的项目补充了母基金，因为它：1）将标记SNP添加到母基金中提到的潜在功能SNP中; 2）添加单倍型分析; 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有关的癌症，是美国男性中第四大常见癌症。事实上，只有一小部分吸烟者患膀胱癌，这表明对这种疾病的遗传易感性。这项研究将确定新的遗传标记可能是有用的生物标志物，以确定高风险人群，然后可以针对干预计划。