权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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）：结直肠癌（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发病率和死亡率在所有美国人群中最高。这些差异尚未得到解释，生物学风险因素，包括遗传易感性CRC在非洲裔美国人研究不足。我是一名胃肠病学家，希望在CRC遗传学领域成为一名独立的翻译医生-科学家。我的长期职业目标需要我获得额外的培训：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进行，该大学在人类和癌症遗传学领域，特别是在混合人群中脱颖而出。我很幸运在北卡罗来纳州大学和伊利诺伊大学芝加哥有重要的合作者，我们一起有来自1000多名非洲裔美国人CRC患者和1000名非洲裔美国人对照受试者的DNA可用于我提议的研究。医学教授兼人类遗传学主任南希考克斯博士是我的导师，她将提供统计遗传学方面的专业知识。医学副教授Nathan Ellis博士是共同导师，将提供CRC分子遗传学方面的专业知识。由混合人群遗传学专家Rick Kittles博士、国际公认的癌症遗传学领导者Olufunmilayo Olopade博士和胃肠病学成功的内科医生兼科学家尤金·张博士组成的跨学科咨询委员会将在此开发期间为我提供指导和建议。这项研究计划的主要目标是确定导致非裔美国人CRC发展风险的遗传易感性因素。我将研究在欧洲人群中使用全基因组关联研究发现的单核苷酸多态性（SNP）。含有这些SNP的区域可能具有功能变体。非裔美国人是一个理想的人口中，以确定功能性变异，因为他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）在非裔美国人病例和对照中筛选候选的CRC相关区域; 2）通过使用下一代测序技术进行靶向重测序，在CRC相关区域中发现新的SNP; 3）在候选的CRC相关区域中鉴定推定的功能变体，这些变体可以在未来的功能研究中进一步评估。在我的职业发展期结束时，我将有能力在CRC遗传学方面进行进一步的转化研究。我的长期研究目标是了解CRC发病机制中的遗传易感性，并研究遗传易感性因素如何用于CRC筛查的风险分层个体，从而预防疾病，特别是在高风险但未充分研究的人群中，如非洲裔美国人。