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：
8268502
负责人：
Jie Lin
金额：
$ 13.75万
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 2013-03-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8268502
关键词：
Address Age Algorithms Alleles American Apoptosis Apoptotic Area 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 Instruction 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 Predictive Value Predisposition Publishing Recruitment Activity Research Personnel Research Project Grants Resources Risk Assessment Sampling Smoker Specimen Statistical Methods Suspension substance Suspensions Tobacco Tobacco smoke Training Variant anticancer research base cancer risk carcinogenesis college coping gene environment interaction gene interaction high risk intervention program medical specialties meetings men new technology novel parent grant sex skills statistics telomere tool

项目摘要

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 analyzehigh throughput gene variant data to explore gene- gene and gene-environment interactions in cancer susceptibility. Mycareer development plan includedidatic courses/seminars, meetings with mentors in the areas of human genetics, cancer biology and advanced statistical methods. Myresearch proposal will focus on genetic susceptibility of blader cancer (BC). I propose to capitalize on availabilityof epidemiologicand genentic marker data from an on-going case-control study, "Markers of GeneticSusceptibilityto Bladder Cancer"(R01 CA74880,PI:Xifeng. Wu). The parent study currently include over 2,500,mostly Caucasian,BCcases and controls, matched on sex, age and ethnicity. Mygoal is to identify novel loci that confer bladder cancer susceptibility using state-of-the-art genotyping techology and novel statistical and bioinformaticstools. 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 DNArepair, cell cycle control and apoptotic pathways in 800 Caucasiancases and 800 Caucasiancontrols using the Illumina Golden Gate Assay; 2) To assess haplotypes and diplotypes as markers of susceptibility; 3) To use bioinformaticstools to assess functional significance of SNPs in the DNArepair, cell cycle control and apoptotic pathways and to correlate genotype data of DNArepair 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 BCrisk. 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 bioinformaticsapproaches. RELEVANCE (See instructions): 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 caricer indicating genetic susceptibility to the disease. This study will identify novel genetic markers may be useful as biomarkers to identify high-risk populationsthat could then be targeted for intervention programs.

我的长期目标是成为一名独立的分子流行病学家，并在遗传学和先进的统计方法，以便能够分析吞吐量基因变异数据以探索基因癌症易感性中的基因和基因环境相互作用。 Mycareer开发计划包括课程/研讨会，与人类遗传学，癌症生物学和先进领域的导师会议统计方法。 MyResearch提案将集中于Blader Cancer（BC）的遗传易感性。我建议利用正在进行的病例对照研究的流行病学和一致标记数据的可用性， “膀胱癌的遗传敏感性标记”（R01 CA74880，PI：Xifeng。Wu）。父母研究目前包括2500多个与性别，年龄和种族相匹配的高加索人，BCCASE和对照。 Mygoal是确定新颖的基因座，可以使用最先进的基因分型技术和新颖统计和生物信息学。具体目的是：1）增强我在遗传学方面的知识和技能通过扩展原始45电位，将新型遗传基因座识别为卑诗省的敏感性标志物功能性SNP，包括在DNAREPAIR中的基因中包含其他2112个标记SNP，细胞周期控制和使用Illumina Golden Gate测定法中800个高加索酶和800种高加索控制的凋亡途径； 2）评估单倍型和外交型作为易感性的标志； 3）使用生物信息源评估 SNP在DNAREPAIR，细胞周期控制和凋亡途径中的功能意义，并相关通过表型测定得出的功能数据，DNAREPAIR和细胞周期控制的基因型数据。这次要目的是应用层次模型来完善风险评估并应用新颖的机器学习探索任何影响Bcrisk的基因环境和基因 - 基因相互作用的工具。我的项目补充了父母的赠款：1）将标记SNP添加到了潜在的功能SNP中在父母赠款中； 2）添加单倍型分析； 3）提出了新颖的统计和生物信息图。相关性（请参阅说明）：膀胱癌是一种与烟草相关的癌症，这是美国男性中第四个最常见的癌症只有一小部分吸烟者会出现膀胱焦糖剂，表明对疾病的遗传敏感性。这研究将识别新的遗传标志物可能是鉴定高风险人群的生物标志物然后可以针对干预计划。