Genetic Association Studies in African American Colorectal Cancer Patients

非裔美国结直肠癌患者的遗传关联研究

基本信息

批准号：
8722856
负责人：
Sonia Kupfer
金额：
$ 16.44万
依托单位：
UNIVERSITY OF CHICAGO
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：
2010-09-17 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8722856
关键词：
15q23 8q24 Advisory Committees Affect African African American American Bioinformatics Biological Cancer Biology Cancer Etiology Cancer Patient Chicago Colorectal Cancer Communities DNA DNA Resequencing Data Databases Development Disease European Exhibits Future Gastroenterologist Gastroenterology Genetic Genetic Predisposition to Disease Genome Goals Human Genetics Illinois Incidence Individual Inherited Lead Linkage Disequilibrium Medicine Mentors Molecular Molecular Genetics Morbidity - disease rate North Carolina Pathogenesis Physicians Population Research Research Proposals Risk Risk Assessment Risk Factors Scientist Series Signal Transduction Single Nucleotide Polymorphism Targeted Resequencing Technology Testing Training Translational Research Universities Validation Variant cancer genetics career career development case control colorectal cancer screening disorder prevention genetic association genome wide association study high risk mortality next generation sequencing novel prevent professor programs public health relevance rare variant

项目摘要

DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is a significant cause of cancer morbidity and mortality affecting almost 150,000 Americans yearly. African Americans have the highest CRC incidence and mortality of all US populations. These disparities have not been explained, and biological risk factors including genetic susceptibility to CRC are understudied in African Americans. I am a gastroenterologist who seeks to develop a career as an independent translational physician-scientist in CRC genetics. My long-term career goals require me to obtain additional training in: 1) molecular and statistical genetics; and 2) cancer biology. The 5-year career development program described in this application will take place at the University of Chicago which distinguishes itself in the field of human and cancer genetics especially in admixed populations. I am fortunate to have key collaborators at the University of North Carolina and the University of Illinois Chicago, and together we have DNA from over 1000 African American CRC patients and 1000 African American control subjects available for my proposed study. Dr. Nancy Cox, Professor of Medicine and Chief of Human Genetics, is my mentor and will provide expertise in statistical genetics. Dr. Nathan Ellis, Associate Professor of Medicine, is a co-mentor and will provide expertise in CRC molecular genetics. An inter-disciplinary Advisory Committee comprised of Dr. Rick Kittles, an expert in genetics of admixed populations, Dr. Olufunmilayo Olopade, an internationally recognized leader in cancer genetics, and Dr. Eugene Chang, a successful physician-scientist in gastroenterology, will guide and advise me during this development period. The broad objectives of this research proposal are the identification of genetic susceptibility factors that contribute to risk of CRC development in African Americans. I will study single nucleotide polymorphisms (SNPs) discovered using genome-wide association studies in European populations. Regions containing these SNP are likely to harbor functional variants. African Americans are an ideal population in whom to identify functional variants because their genomes exhibit less linkage disequilibrium. To this end, I propose three specific aims: 1) Validate candidate CRC-associated regions in African American cases and controls; 2) Discover novel SNPs in CRC-associated regions by targeted resequencing using next-generation sequencing technologies; and 3) Identify putative functional variants in candidate CRC-associated regions that can be further evaluated in future functional studies. By the end of my career development period, I will be uniquely equipped to undertake further translational research in CRC genetics. My long-term research goals are to understand genetic susceptibility in CRC pathogenesis and to study how genetic susceptibility factors can be used to risk stratify individuals for CRC screening and thereby prevent disease especially in high risk but understudied populations like African Americans.

描述（由申请人提供）：大肠癌（CRC）是癌症发病率和死亡率的重要原因，每年影响近15万美国人。非裔美国人的CRC发病率和死亡率最高。这些差异尚未得到解释，在非洲裔美国人中研究了包括遗传易感性在内的生物危险因素。我是一名胃肠病学家，他试图发展CRC遗传学的独立翻译医师科学家的职业。我的长期职业目标要求我在以下方面获得额外的培训：1）分子和统计遗传学； 2）癌症生物学。本申请中描述的5年职业发展计划将在芝加哥大学举行，该计划在人类和癌症遗传学领域，尤其是在混杂的人群中。我很幸运能在北卡罗来纳大学和伊利诺伊大学芝加哥大学拥有主要的合作者，我们共有1000多名非裔美国人CRC患者和1000名非裔美国人对照科目的DNA，可用于我的拟议研究。医学教授兼人类遗传学负责人南希·考克斯（Nancy Cox）是我的导师，将提供统计遗传学的专业知识。医学副教授内森·埃利斯（Nathan Ellis）博士是一名同事，将提供CRC分子遗传学的专业知识。一个跨学科的咨询委员会由Rick Kittles博士组成，Rick Kittles博士是混合人群遗传学专家，Olufunmilayo Olopade博士，癌症遗传学的国际认可的领导者Olufunmilayo Olopade博士，以及成功的医生 - 科学家Eugene Chang博士，将在胃肠病学领域进行研究，并在此开发期间为我提供指导和建议。该研究建议的广泛目标是确定遗传易感性因素，这些因素导致非洲裔美国人发生CRC的风险。我将研究使用欧洲人群中全基因组关联研究发现的单核苷酸多态性（SNP）。包含这些SNP的区域可能具有功能变体。非洲裔美国人是一个理想的人群，可以在其中识别功能变异，因为它们的基因组表现出较少的连锁不平衡。为此，我提出了三个具体目标：1）在非裔美国人案件和对照中验证候选人与CRC相关的地区； 2）通过使用下一代测序技术靶向重新取证CRC相关区域中的新型SNP； 3）在候选CRC相关区域中确定推定的功能变体，这些变体可以在未来的功能研究中进一步评估。在我职业发展期结束时，我将拥有独特的能力进行CRC遗传学的进一步转化研究。我的长期研究目标是了解CRC发病机理中的遗传敏感性，并研究如何使用遗传易感性因素来使个人进行CRC筛查分层，从而预防疾病，尤其是在高风险中，但像非洲裔美国人这样的人口进行了研究。