A Multiethnic Genome-Wide Scan of Prostate Cancer

前列腺癌的多种族全基因组扫描

基本信息

批准号：
7762619
负责人：
Christopher Alan Haiman
金额：
$ 40.8万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-20 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7762619
关键词：
8q24 Accounting Affect African African American Age Alleles American Androgens Candidate Disease Gene Chromosomes Cohort Studies Collaborations Communities Copy Number Polymorphism DNA Data Data Collection Data Set Detection Development Diagnosis Disease Early Diagnosis Environment Environmental Risk Factor Epidemiologic Studies Ethnic group Etiology European Familial disease Family Study Family history of First Degree Relative Future Genes Genetic Genetic Heterogeneity Genetic Variation Genotype Grant Hawaiian population Heterogeneity Individual Inherited Investments Japanese American Knowledge Latino Life Style Malignant neoplasm of prostate Maps Measures Minority Morbidity - disease rate Pan Genus Pathway interactions Play Policies Population Preventive Regulation Research Personnel Resources Risk Risk Factors Role Sampling Severity of illness Single Nucleotide Polymorphism Subgroup Testing Therapeutic Twin Multiple Birth United States National Institutes of Health Variant Work analytical method anticancer research base cancer genetics cancer risk cohort disorder risk gene interaction genetic association genetic linkage analysis genetic risk factor genetic variant genome wide association study insight male men mortality non-genetic novel prognostic racial and ethnic

项目摘要

DESCRIPTION (provided by applicant): Prostate cancer is a leading cause of morbidity and mortality among men. Risk factors for prostate cancer have remained elusive and aside from age, having a family history of the disease or African ancestry, until recently, no genetic or non-genetic (i.e. lifestyle) risk factors have been consistently demonstrated to contribute to variation in disease risk in the population. Over the past year, we contributed to the first reproducible genetic risk factor for prostate cancer at 8q24. Through fine-mapping of 8q24 in five racial/ethnic populations in the Multiethnic Cohort Study (MEC), we identified three regions that contain 7 independent risk variants for prostate cancer. Only some of these variants were found in studies conducted in European Whites, thus, emphasizing the power of genetic studies in multiple racial/ethnic populations to reveal a more complete spectrum of variants associated with disease risk. In this application, we propose to work with the GEI-GWA Steering Committee to identify genetic factors that contribute to prostate cancer by performing a well-powered genome-wide association study among African American, Japanese American, Native Hawaiian, Latino and European American men in the MEC. More specifically, we propose the genotyping of approximately 1,000,000 single nucleotide polymorphisms (SNPs) and >940,000 probes to detect copy number variation in 3,750 prostate cancer cases and 3,750 controls, to identify pan-ethnic genetic variants that affect risk in all five racial/ethnic populations, as well as important ethnic-specific variation. In this multi-ethnic dataset, we will also examine interaction between associated variants, environmental factors (thereby better defining the role of these factors) and disease severity, as well as explore the causes of heterogeneity of genetic effects across populations. We have also established collaborations with other prostate cancer researches to replicate the ethnic-specific associations observed in this GWA study in minority populations. We expect this work to significantly advance knowledge of the etiology of prostate cancer across these racial/ethnic populations, guiding the development of future preventive, early detection, prognostic and even therapeutic measures.

描述（由申请人提供）：前列腺癌是男性发病率和死亡率的主要原因。前列腺癌的危险因素仍然难以捉摸，除了年龄，具有疾病或非洲血统的家族史，直到最近，始终如一地证明，尚无遗传或非遗传或非遗传或非遗传（即生活方式）危险因素有助于疾病风险的变化。在过去的一年中，我们为前列腺癌的第8季度第8季度贡献了第一个可再现的遗传危险因素。通过在多民族队列研究（MEC）中五个种族/族裔人群中的8q24绘制，我们确定了三个区域，这些区域包含7种独立的前列腺癌风险变体。在欧洲白人进行的研究中，仅发现其中一些变体，因此强调了多个种族/族裔人群中遗传研究的力量，以揭示与疾病风险相关的更完整的变体。在此应用中，我们建议与GEI-GWA指导委员会合作，以确定对前列腺癌的遗传因素，通过对MEC中非洲裔美国人，日裔美国人，夏威夷人，拉丁裔和欧洲男性进行全基因组范围的关联研究。更具体地说，我们提出了大约1,000,000个单核苷酸多态性（SNP）和> 940,000个探针的基因分型，以检测3,750个前列腺癌病例和3,750例对照中的拷贝数变化，以识别所有五个种族/种族群体的风险，以及重要的民族种群，以及重要的民族族裔，以及重要的eNticnic-extecixic variation。在这个多种族数据集中，我们还将研究相关变体之间的相互作用，环境因素（从而更好地定义这些因素的作用）和疾病的严重程度，并探讨跨种群遗传效应异质性的原因。我们还与其他前列腺癌研究建立了合作，以复制这项在GWA研究中在少数民族人群中观察到的种族特异性关联。我们希望这项工作能够大大提高这些种族/族裔人群中前列腺癌病因的了解，从而指导未来预防，早期检测，预后甚至治疗措施的发展。