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Polymorphisms in Inflammation Genes and Bladder Cancer Risk

炎症基因多态性与膀胱癌风险

基本信息

批准号：
7458073
负责人：
Jian Gu
金额：
$ 7.7万
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：
2007
资助国家：
美国
起止时间：
2007-07-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7458073
关键词：
Address Age Algorithms Biological Biological Assay Biology Bladder Cancer Center Cancer Etiology Candidate Disease Gene Case-Control Studies Caucasians Caucasoid Race Cell Cycle Cell Cycle Regulation Cells Clinic Clinical Complex Cytogenetics DNA DNA Repair Data Databases Disease Doctor of Medicine Doctor of Philosophy Environment Environmental Risk Factor Erythrocytes Ethnic Origin Etiology Frequencies Funding Gender Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Genetic Risk Genomic Instability Genomics Genotype Goals Haplotypes Individual Individual Differences Inflammation Interleukin-6 Length Literature Lymphocyte Machine Learning Malignant Neoplasms Malignant neoplasm of urinary bladder Medicine Modeling Molecular Mutagens Newly Diagnosed Pathway interactions Pattern Penetrance Physicians Plasma Play Predisposition Research Personnel Risk Risk Assessment Role Sampling Significance Level Specimen Statistical Methods Susceptibility Gene Suspension substance Suspensions Telomere Maintenance Testing Variant base cancer risk carcinogenesis college follow-up gene environment interaction gene interaction medical specialties multidisciplinary novel parent grant promoter repository telomere tool

项目摘要

DESCRIPTION (provided by applicant): This proposed study will build upon the extensive epidemiologic database and specimen repository derived from an ongoing bladder cancer study entitled "Genetic Susceptibility to Bladder Cancer: A Molecular Epidemiologic Approach" (RO1 CA74880, PI: Xifeng Wu). The parent grant involved a multidisciplinary group of researchers applying a molecular epidemiologic approach to identify inter-individual differences in susceptibility to bladder carcinogenesis, with a focus on genes involved in protecting against genomic instability, such as DNA repair, cell cycle, and telomere maintenance. It is increasing recognized that inflammation plays an important role in the etiology of many cancers, including bladder cancer (BC). We have recently shown that an IL-6 promoter SNP (G-174C) is associated with BC risk and progression. In this application, we will test the hypothesis that BC is modulated by common, low penetrance polymorphisms in inflammation related genes, interacting with each other and/or environmental factors. We will take a pathway based genotyping approach and apply novel statistical tools to address the hypothesis. There are 3 specific aims: Specific Aim 1: To identify candidate polymorphisms in inflammation related genes that predispose individuals to BC. We plan to perform genotyping of a comprehensive list of potential functional polymorphisms in inflammation genes (85 polymorphisms in 44 genes) on 1000 Caucasian cases and 1000 controls matched on age, gender, and ethnicity. Specific Aim 2: To perform genotyping on tagging SNPs for the top 8 candidate genes that were identified in Specific Aim 1 (using a significance level of 0.1) identified in Specific Aim 1. This will give us a complete picture of the role that the specific gene plays in BC etiology. We will implement haplotype-based analyses to identify any additional variants that might have been missed using individual SNP-based approaches. Specific Aim 3: To apply hierarchical models to refine risk assessment and to apply novel machine-learning tools to identify any gene-environment and gene- gene interactions influencing risk for BC. These analyses will examine SNP main effects and gene-gene interactions, gene-environment interaction and develop and validate algorithms, which will identify individuals at highest risk for BC, given their personal exposure patterns and their genetic risk profiles. The application will allow us to have a comprehensive picture of the effects of functional polymorphisms in inflammation related genes on BC risk.

描述（由申请人提供）：