Adding Hispanics to Ongoing GWAS in Colorectal Cancer

将西班牙裔纳入正在进行的结直肠癌 GWAS 中

• 批准号: 8317598
• 负责人: Jane C. Figueiredo
• 金额: $ 111.62万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-09 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8317598
• 关键词: 8q24; Address; Admixture; African American; Age; Alleles; Area; California; Cohort Studies; Colorectal Cancer; Complement; Country; Data; Data Collection; Diagnosis; Diet; Disease; Environment; Ethnic Origin; Ethnic group; Etiology; Family; Family history of; Funding; Gene Frequency; Genes; Genetic; Genetic Predisposition to Disease; Genotype; Growth; Haplotypes; Heterogeneity; High Prevalence; Hispanics; Hormones; Human Genome; Incidence; Individual; Investigation; Investments; Japanese Population; Life; Malignant Neoplasms; Maps; Methodology; Mexico; Microsatellite Instability; Not Hispanic or Latino; Obesity; Pathology Report; Population; Population Attributable Risks; Predisposition; Puerto Rican; Questionnaires; Race; Recording of previous events; Recruitment Activity; Research; Resources; Risk; Risk Estimate; Risk Factors; Role; Sampling; Staging; Testing; Tumor Subtype; United States National Institutes of Health; Woman; base; case control; colon cancer family registry; cost; early onset; epidemiologic data; gene environment interaction; genetic resource; genome wide association study; men; mortality; neoplasm registry; novel; population based; racial and ethnic; racial and ethnic disparities; tumor

DESCRIPTION (provided by applicant): Genome-wide association studies (GWAS) of colorectal cancer (CRC) have been instrumental in identifying a number of common susceptibility loci in Non Hispanic (NH)-White populations and a NCI priority is to extend GWAS findings to other populations to address racial/ethnic disparities in cancer susceptibility. Currently, GWA studies of CRC in NH-Whites, Japanese and African-Americans are ongoing. We propose a complementary study to address this critical research area in Hispanics. Hispanics represent the fastest growing ethnic population in the U.S. and have been largely understudied in terms of genetic susceptibility to cancer. There are noted differences in incidence, survival and mortality in CRC by ethnic/racial groups. Hispanics often present with CRC at a younger age and have a significantly greater incidence of stage IV tumors or metastatic disease compared to NH-Whites. We propose to conduct a large, cost-efficient, population-based GWAS in Hispanics by building upon existing NIH-funded resources, the Colon Cancer Family Registry (Colon CFR) and the Multiethnic Cohort Study (MEC). We plan to recruit 2,500 Hispanic men and women diagnosed with CRC between 01/2010 to 10/2013 using cancer registries in California. Risk factor/diet questionnaires, pathology reports, Oragene buccal samples (for genotyping) and tumor blocks (for MSI testing) will be collected using methodologies developed in the Colon CFR/MEC. Cases of CRC in the MEC (currently 473; anticipated 600 at end) will also be included. Population-based Hispanic individuals without a diagnosis of CRC participating in other GWA studies in the MEC (n=3,900, U01HG004726, Haiman) will be used as controls. We will genotype all 3,100 cases using the Illumina 1M array and use available genotype and epidemiologic data collected on 3,900 controls. Our statistical analyses will include: single-SNP and haplotype effects, gene-environment interactions and heterogeneity by MSI, tumor subtype and family history of CRC. We will replicate findings in a second-stage using CRC cases and controls from Mexico (1,000 cases and 1,000 controls, EU FP7 funding, CHIBCHA, Carvajal-Carmona/Tomlinson). We will also examine heterogeneity of the risk estimates by ethnicity/race by leveraging GWA data on NH-Whites (2,142 cases, 1,909 controls, U01 CA122839, Casey), (4,000 cases, 6,000 NH-White controls, UK-CHIBCHA, Tomlinson), Colombians (2,000 cases and 2,000 controls, CHIBCHA), Japanese (1,000 cases and 1,000 controls) and African-Americans (1,500 cases and 1,500 controls, R01CA126895, Le Marchand). We will genotype replicated significant SNPs in our main and combined analysis in several Hispanic populations (note: studies funded by EU or NIH for data collection but not GWAS) including: 800 Puerto Ricans, 2,000 Brazilians, 2,000 Argentineans and 3,000 Spanish/Portuguese to assess generalizability of findings. This study will have a high impact by addressing the key question of racial/ethnic disparities related to genetic susceptibility to CRC, and will enable further growth and investment into research among Hispanics by providing a resource of genetic data and biospecimens, which is lacking.

描述（由申请人提供）：结直肠癌（CRC）的全基因组关联研究（GWA）对识别非西班牙裔（NH） - 白人群体中的许多常见易感性基因座和NCI优先级是为了解决其他种群的发现，以解决其他种族/种族的疾病，以解决其他种族/种族的疾病。目前，GWA对NH-Whites，日本和非裔美国人的CRC研究正在进行中。我们提出了一项补充研究，以解决西班牙裔研究领域的关键研究领域。西班牙裔是美国增长最快的种族人口，并且在遗传易感性方面已在很大程度上被研究了。族裔/种族群体在CRC的发病率，生存和死亡率上有注意。与NH-Whites相比，西班牙裔经常出现在年轻时的CRC，并且IV期肿瘤或转移性疾病的发生率明显更高。我们建议通过基于现有的NIH资助资源，结肠癌家族登记局（Colon CFR）和多种族同龄人群研究（MEC）来建立大型，成本效益，基于人群的GWAS。我们计划使用加利福尼亚州的癌症注册表招募2,500名西班牙裔男女在01/2010到10/2013之间被诊断出患有CRC的男女。风险因素/饮食问卷，病理报告，Oragene颊样品（用于基因分型）和肿瘤块（用于MSI测试）将使用CFR/MEC中开发的方法收集。还将包括MEC中的CRC病例（目前为473；预计将结束600例）。基于人群的西班牙裔人没有CRC诊断为MEC的其他GWA研究（n = 3,900，U01HG004726，Haiman），将用作对照。我们将使用Illumina 1M阵列进行基因型所有3,100例病例，并使用可用的基因型和在3,900个对照中收集的流行病学数据。我们的统计分析将包括：单SNP和单倍型效应，MSI，肿瘤亚型和CRC家族史的基因环境相互作用以及异质性。我们将使用墨西哥的CRC案例和对照（1,000例和1,000个对照，欧盟FP7资金，Chibcha，Chibcha，Carvajal-Carmona/Tomlinson）在第二阶段复制发现。 We will also examine heterogeneity of the risk estimates by ethnicity/race by leveraging GWA data on NH-Whites (2,142 cases, 1,909 controls, U01 CA122839, Casey), (4,000 cases, 6,000 NH-White controls, UK-CHIBCHA, Tomlinson), Colombians (2,000 cases and 2,000 controls, CHIBCHA), Japanese (1,000 cases and 1,000个对照）和非裔美国人（1,500例和1,500例对照，R01CA126895，Le Marchand）。我们将基因型在几个西班牙裔人群中的主要和联合分析中复制了重要的SNP（注意：由欧盟或NIH资助的数据收集，但不是GWAS资助），其中包括：800名波多黎各人，2,000名巴西，2,000名阿根廷人和3,000个西班牙/葡萄牙语，以评估发现结果的普遍性。这项研究将通过解决与CRC遗传易感性有关的种族/种族差异的关键问题，并将产生很大的影响，并通过提供缺乏的遗传数据和生物测量资源来实现西班牙裔研究的进一步增长和投资。