Genomewide Association Study of Prostate Cancer

前列腺癌全基因组关联研究

• 批准号: 7927034
• 负责人: John S. Witte
• 金额: $ 116.26万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-18 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7927034
• 关键词: 8q24; African American; Age; Asian Americans; California; Cancer Etiology; Candidate Disease Gene; Caucasians; Caucasoid Race; Chromosomes; Complex; DNA; Data; Disease; Ethnic Origin; Ethnic group; Finding by Cause; Genes; Genetic; Genetic Markers; Genome; Genomics; Genotype; Haplotypes; Individual; International; Length; Light; Malignant neoplasm of prostate; Maps; Measures; Minority; Modality; Morbidity - disease rate; National Cancer Institute; Nested Case-Control Study; Oncogenes; Penetrance; Population; Population Study; Predisposition; Process; Prostate; Race; Risk; Risk Factors; Saliva; Sample Size; Screening procedure; Single Nucleotide Polymorphism; Specific qualifier value; Staging; Structure of base of prostate; Study Subject; System; Testing; Tumor Suppressor Genes; Variant; Work; cancer genetics; cancer genome; cancer risk; carcinogenesis; case control; cohort; cost; design; follow-up; genetic risk factor; genetic variant; genome wide association study; genome-wide linkage; improved; male health; man; men; mortality; novel; public health relevance

DESCRIPTION (provided by applicant): The morbidity and mortality due to prostate cancer varies substantially across ethnic groups, and there is clear evidence that genetic factors impact a man's risk of prostate cancer. However, finding genetic variants that cause this common but complex disease has proven difficult. Traditional genome-wide linkage and candidate gene studies have produced equivocal results. This is due in part to the reduced power of linkage studies to detect common variants with modest effects and the limited number of genes evaluated in candidate gene studies. A more promising approach is to search for prostate cancer causing genetic variants using a genome- wide association study of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Recent GWAs of prostate cancer focused on Caucasians have detected a number of extremely promising associations. We propose building on these exciting results with large a genome-wide association study of how SNPs and CNVs impact prostate cancer risk in minority populations. Specifically, we will study 2,000 prostate cancer cases and 2,000 age and ethnicity matched controls (2,000 African-Americans, and 2,000 Asian-Americans) nested in the Northern California Kaiser Permanente population. Our first aim is to obtain biospecimens on this nested case-control population. Second, we will genotype the new Affymetrix SNP Array 6.0 on the entire study population. This single-stage design is highly efficient in light of the rapidly decreasing genotyping costs, and is necessary to fully evaluate both SNPs and CNVs. Our third aim will investigate the association between the SNPs measured by the Array and prostate cancer. Fourth, we will determine CNVs from the Array, and evaluate how they effect prostate cancer risk (i.e., alone and in conjunction with the SNPs). The study sample size of 4,000 subjects and the comprehensive SNP Array 6.0 information provide sufficient power for detecting SNP and CNV associations with prostate cancer. By focusing this genome-wide association study on the two ethnic groups with the highest and lowest risks of prostate cancer and studying subjects from the highly representative Kaiser Permanente population this project provides an outstanding opportunity to determine the genetic causes of this disease in understudied populations. Finding such genetic factors will have substantial significance with regard to improving screening, treatment modalities, and understanding the biologic basis of prostate cancer. PUBLIC HEALTH RELEVANCE: Prostate cancer is one of the most common and clearly familial / genetic cancers, but finding the cause of this disease has proven extremely difficult. Our efforts toward deciphering the genetic basis of prostate cancer in minority populations will help improve screening, treatment, and our overall understanding of this disease. These advances will improve the overall health of men, providing much needed information about individual- and population-level risks of prostate cancer within understudied populations.

描述（由申请人提供）：前列腺癌引起的发病率和死亡率在各个族群之间有很大差异，并且有明确的证据表明遗传因素会影响男人患前列腺癌的风险。但是，发现引起这种常见但复杂疾病的遗传变异已被证明很困难。传统的全基因组联系和候选基因研究产生了模棱两可的结果。这部分是由于连锁研究能力降低了检测具有适度效应的常见变体以及在候选基因研究中评估的基因数量有限。一种更有前途的方法是使用单核苷酸多态性（SNP）和拷贝数变体（CNV）的基因组范围研究来寻找前列腺癌，从而引起遗传变异。前列腺癌的最近重点是高加索人，已经发现了许多极为有希望的关联。我们提出了对这些令人兴奋的结果的建立，其中大量基因组的关联研究对SNP和CNV如何影响少数族裔人群的前列腺癌风险。具体来说，我们将研究2,000例前列腺癌病例和2,000次年龄和种族与对照组（2,000名非裔美国人和2,000名亚裔美国人）相匹配，该癌症是嵌套在北加州Kaiser Permanente人口中的。我们的第一个目的是在此嵌套的病例对照人群上获取生物测量。其次，我们将在整个研究人群中基因型新的Affymetrix SNP阵列6.0。鉴于基因分型成本迅速降低，这种单阶段的设计非常有效，并且对于完全评估SNP和CNV是必要的。我们的第三个目标将调查阵列和前列腺癌测量的SNP之间的关联。第四，我们将确定阵列中的CNV，并评估它们如何影响前列腺癌风险（即单独，与SNP结合使用）。研究样本量的4,000名受试者和全面的SNP阵列6.0信息为检测与前列腺癌的SNP和CNV关联提供了足够的功率。通过将这项全基因组关联研究集中在两个族群上，这些族群具有前列腺癌风险最高和最低风险，并研究了高度代表性的Kaiser Permanente人群的受试者，该项目为确定研究研究型疾病的遗传原因提供了一个绝佳的机会。在改善筛查，治疗方式和理解前列腺癌的生物学基础方面，发现这种遗传因素将具有重要意义。公共卫生相关性：前列腺癌是最常见，最明显的家族 /遗传癌症之一，但是发现这种疾病的原因已被证明非常困难。我们为在少数族裔种群中破译前列腺癌的遗传基础的努力将有助于改善筛查，治疗以及我们对这种疾病的整体理解。这些进步将改善男性的整体健康状况，提供有关研究范围内人群中前列腺癌的个人和人口水平风险的急需信息。