Genome Wide Association Study of Head and Neck Cancer

头颈癌全基因组关联研究

基本信息

批准号：
8434277
负责人：
Sanjay Shete
金额：
$ 47.27万
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：
2009-03-01 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8434277
关键词：
African American Age Alcohol consumption Alcohols Area Behavioral Benzo(a)pyrene Biological Biological Assay CCRL2 gene Cancer Center Cancer Etiology Cancer Patient Case Study Case-Control Studies Caucasians Caucasoid Race Cells Cessation of life Chromosome abnormality Classification Clinic Visits Control Groups County Custom DNA DNA Adducts DNA Repair DNA Repository Data Databases Development Disease Early Diagnosis Enrollment Environment Environmental Carcinogens Environmental Risk Factor Epidemiology Ethnic Origin Exposure to Freedom Frequencies Funding Gender Gene Frequency Genes Genetic Polymorphism Genetic Predisposition to Disease Genetic Risk Genomics Genotype Goals Haplotypes Head and Neck Cancer Head and neck structure Health Hispanic Americans Histologic In Vitro Individual Inherited Joints Larynx Lung Lymphocyte Machine Learning Malignant Neoplasms Malignant Squamous Cell Neoplasm Malignant neoplasm of lung Measures Mutagens Oral cavity Outcome Parents Patients Pattern Pharyngeal structure Phase Phenotype Polymorphism Analysis Population Population Control Questionnaires Reporter Genes Research Research Personnel Residencies Risk Role Sampling Scanning Single Nucleotide Polymorphism Smoker Smoking Source Squamous Cell Staging Structure Study models Testing Tobacco Trees Trust United States United States National Institutes of Health adduct alcohol exposure base cancer genome cancer risk case control density disease phenotype experience gene environment interaction genetic risk factor genome wide association study genome-wide high risk metropolitan novel plasmid DNA population based sex text searching tobacco exposure tool

项目摘要

DESCRIPTION (provided by applicant): Head and neck cancers have well-documented associations with tobacco and alcohol exposure, but the disease develops in only a small fraction of users, which implies an important role for genetic susceptibility. Therefore, head and neck cancers are an excellent model for studying genetic susceptibility to environmental carcinogens. The primary goal of this R01 application is to perform a comprehensive two-stage, high-density, genome-wide single-nucleotide polymorphism (SNP) analysis of head and neck cancer cases and corresponding frequency matched controls to identify novel genetic risk factors for head and neck cancer. This proposal builds upon a well-annotated existing DNA repository of cases and controls. One of the unique features of our study is the availability of DNA repair assay data on most of the cases and controls in this study, which will allow us to conduct genotype/phenotype analyses. We also have access to genome-wide association data from 1200 white control subjects from the same source population. In aim 1, we will perform genotyping on 1000 randomly selected head and neck cancer cases and 500 controls using a 370K Illumina Infinium HapMap HumanCNV370-Duo SNP Chip. We will perform association analyses (1000 cases and 1700 controls) in the first stage using outcome variable as case-control status as well as DNA repair capacity assay data. Our second aim is to perform second-stage analysis of the SNPs selected in stage 1 using 900 additional cases and corresponding controls from the same source and from UCLA. We will use efficient joint analysis of cases and controls from the first and second aims, for a total of 1900 cases and 2600 controls. Finally, in aim 3, we will apply novel statistical tools such as the latent variable approach with Tukey's one-degree-of-freedom test and support vector machines to identify gene-gene and gene-environment (using environmental factors such as smoking and alcohol use) interactions that contribute to the risk of head and neck cancer. We are an experienced investigative team proposing a comprehensive analysis that incorporates epidemiological, behavioral, and functional data. Identification of novel genetic risk factors and their interactions with environmental factors will contribute to the early diagnosis of head and neck cancers.

描述（由申请人提供）：头颈癌与烟草和酒精暴露的关系已有充分记录，但只有一小部分使用者会患上这种疾病，这意味着遗传易感性发挥着重要作用。因此，头颈癌是研究环境致癌物遗传易感性的绝佳模型。该 R01 应用程序的主要目标是对头颈癌病例和相应的频率匹配对照进行全面的两阶段、高密度、全基因组单核苷酸多态性 (SNP) 分析，以识别头颈癌的新遗传风险因素。和颈部癌症。该提案建立在一个注释良好的现有案例和对照 DNA 存储库的基础上。我们研究的独特之处之一是可以获得本研究中大多数病例和对照的 DNA 修复测定数据，这将使我们能够进行基因型/表型分析。我们还可以获得来自同一来源人群的 1200 名白人对照受试者的全基因组关联数据。在目标 1 中，我们将使用 370K Illumina Infinium HapMap HumanCNV370-Duo SNP 芯片对 1000 个随机选择的头颈癌病例和 500 个对照进行基因分型。我们将在第一阶段使用结果变量作为病例对照状态以及 DNA 修复能力测定数据进行关联分析（1000 个病例和 1700 个对照）。我们的第二个目标是使用来自同一来源和加州大学洛杉矶分校的 900 个额外病例和相应对照，对第一阶段选择的 SNP 进行第二阶段分析。我们将对第一个和第二个目标的病例和对照进行有效的联合分析，总共 1900 个病例和 2600 个对照。最后，在目标 3 中，我们将应用新颖的统计工具，例如使用 Tukey 的单自由度测试和支持向量机的潜在变量方法来识别基因-基因和基因-环境（使用吸烟和饮酒等环境因素）使用）相互作用会增加头颈癌的风险。我们是一支经验丰富的调查团队，提出结合流行病学、行为和功能数据的全面分析。识别新的遗传风险因素及其与环境因素的相互作用将有助于头颈癌的早期诊断。