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Epidemiologic Studies

流行病学研究

基本信息

批准号：
7933411
负责人：
PETER KRAFT
金额：
$ 30.06万
依托单位：
HARVARD SCHOOL OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7933411
关键词：
Accounting Address Affect Alcohol consumption Algorithms Alleles Architecture BRCA2 Mutation Biology Breast Breast Cancer Detection Breast Cancer Risk Factor Cancer Biology Cancer Etiology Cancer Intervention Case-Control Studies Chemoprevention Chemopreventive Agent Clinical Clinical Trials Collection Data Databases Epidemiologic Studies Epidemiology Family Family history of Genes Genetic Genetic Risk Genotype Guidelines Height Heritability Hormones Incidence Individual Instruction International Intervention Intervention Studies Joints Lead Malignant neoplasm of prostate Modeling Modification National Surgical Adjuvant Breast and Bowel Project Nested Case-Control Study Performance Placebos Population Population Attributable Risks Postmenopause Prevention Primary Prevention Public Health Public Health Applications Research Public Health Practice Relative Risks Reporting Reproductive History Resources Risk Risk Factors Scanning Sensitivity and Specificity Tamoxifen Testing Time Translations Variant Woman Women&apos s Health base breast cancer family registry cancer risk cohort early onset gene environment interaction gene interaction genome wide association study high risk hormone therapy killings malignant breast neoplasm modifiable risk novel marker prophylactic protective effect reproductive treatment strategy trial comparing

项目摘要

Summary. Sub-Project 3 (Epidemiology: genes, modifiable risk factors, and risk prediction for breast cancer) will extend existing genome-wide association studies (GWAS) as well as the additional discovery efforts in Sub-Project 1 of this application by characterizing the relationships among newly-discovered common breast cancer risk alleles, known breast cancer risk factors, and breast cancer incidence. This Sub-Project will accelerate the translation of GWAS findings to clinical and public health practice by suggesting particular biologic mechanisms for breast cancer etiology (Aims 1-3) and by evaluating the clinical validity and utility of genetic risk prediction models in a variety of settings (Aims 4-6). The Sub-Project encompasses six specific aims: 1) Conduct a GWAS for new loci that interact with other, known breast cancer alleles; 2) assess gene-gene interactions among known breast cancer risk alleles; 3) assess gene-environment interactions between known breast cancer risk alleles and established risk factors, most notably modifiable exposures such as postmenopausal hormone therapy; 4) construct and compare the clinical validity of risk prediction algorithms that combine information on multiple breast cancer alleles and known risk factors; 5) evaluate the performance of these algorithms in high-risk families; and 6) assess genetic modification of prophylactic tamoxifen treatment.

摘要子项目3（流行病学：乳腺癌的基因、可改变的风险因素和风险预测）将通过表征新发现的常见乳腺癌风险等位基因、已知乳腺癌风险因素和乳腺癌发病率之间的关系，扩展现有的全基因组关联研究（GWAS）以及本申请子项目1中的额外发现工作。该子项目将通过提出乳腺癌病因学的特定生物学机制（目标1-3）和评估遗传风险预测模型在各种环境中的临床有效性和实用性（目标4-6），加速GWAS发现向临床和公共卫生实践的转化。该子项目包括六个具体目标：1）针对与以下因素相互作用的新位点进行GWAS：其他已知的乳腺癌等位基因; 2）评估已知的乳腺癌风险等位基因之间的基因-基因相互作用; 3）评估已知的乳腺癌风险等位基因和确定的风险因素之间的基因-环境相互作用，最显著的是可改变的暴露，如绝经后激素治疗; 4）构建并比较风险预测算法的临床有效性，所述风险预测算法结合关于多个乳腺癌等位基因和已知风险因素的联合收割机信息; 5）评估这些算法在高风险家庭中的性能;以及6）评估预防性他莫昔芬治疗的遗传修饰。