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：
7777355
负责人：
Sanjay Shete
金额：
$ 60.35万
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 2014-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7777355
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 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 Hispanics 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 Smoke Smoker Smoking Source Squamous Cell Staging Structure Study models Testing Tobacco Trees Trust United States 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 public health relevance repository sex text searching 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. PUBLIC HEALTH RELEVANCE: The identification of novel genetic risk factors and their interactions with environmental factors will contribute to the early diagnosis of the disease and help identify individuals at highest risk for the development of head and neck cancer on the basis of their personal exposure patterns and their genetic risk profiles.

描述（由申请人提供）：头部和颈部癌症与烟草和酒精暴露有据可查的关联，但该疾病仅在一小部分用户中发展，这意味着遗传易感性的重要作用。因此，头颈癌是研究对环境致癌物的遗传敏感性的绝佳模型。该R01应用的主要目标是对头颈癌病例和相应的频率对照组进行全面的两阶段，高密度，全基因组的单核苷酸多态性（SNP）分析，以识别头颈癌的新型遗传风险因素。该提案建立在案件和控件的现有DNA存储库中。我们研究的独特特征之一是本研究中大多数病例和对照的DNA修复测定数据的可用性，这将使我们能够进行基因型/表型分析。我们还可以访问来自同一源人群的1200名白人控制受试者的全基因组关联数据。在AIM 1中，我们将使用370K Illumina Infinium hapmap Humancnv370-Duo SNP 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维修能力测定数据进行关联分析（1000例和1700个对照）。我们的第二个目的是使用900个其他情况以及来自同一源和UCLA的相应控件对在第1阶段中选择的SNP进行第二阶段分析。我们将对从第一个和第二个目标进行有效的案例和对照联合分析，共有1900例和2600个对照。最后，在AIM 3中，我们将使用Tukey的一级自由测试和支持向量机器应用新颖的统计工具，例如潜在可变方法，以鉴定基因基因和基因环境（使用诸如吸烟和酒精使用之类的环境因素）相互作用，从而有助于头和颈部癌的风险。我们是一个经验丰富的调查团队，提出了一项综合分析，该分析结合了流行病学，行为和功能数据。鉴定新的遗传危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。公共卫生相关性：鉴定新的遗传危险因素及其与环境因素的相互作用将有助于早期诊断该疾病，并帮助识别出根据其个人暴露模式及其遗传风险概况的头和颈癌发展最高风险的人。