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: 8856513
• 负责人: Jane C. Figueiredo
• 金额: $ 56.51万
• 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 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8856513
• 关键词: 8q24; Address; Admixture; African American; Age; 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; Hormone use; 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; Susceptibility Gene; 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 (GWAS) 有助于确定非西班牙裔 (NH) 白人群体中的许多常见易感位点，NCI 的首要任务是扩展 GWAS 研究结果向其他人群提供帮助，以解决癌症易感性方面的种族/民族差异。目前，GWA 对新罕布什尔州白人、日本人和非洲裔美国人的 CRC 研究正在进行中。我们提出一项补充研究来解决西班牙裔的这一关键研究领域。西班牙裔是美国增长最快的族裔人口，但在癌症遗传易感性方面的研究在很大程度上还不够充分。不同种族/种族群体的结直肠癌发病率、生存率和死亡率存在显着差异。与非白人白人相比，西班牙裔人患结直肠癌的年龄通常更小，且 IV 期肿瘤或转移性疾病的发生率明显更高。我们建议利用 NIH 资助的现有资源、结肠癌家族登记处 (Colon CFR) 和多种族队列研究 (MEC)，在西班牙裔人群中开展大规模、经济高效、以人群为基础的 GWAS。我们计划利用加利福尼亚州的癌症登记处招募 2,500 名在 2010 年 1 月至 10 月期间被诊断患有 CRC 的西班牙裔男性和女性。将使用 Colon CFR/MEC 中开发的方法收集危险因素/饮食调查问卷、病理报告、Oragene 口腔样本（用于基因分型）和肿瘤块（用于 MSI 测试）。 MEC 中的 CRC 病例（目前为 473 例；预计最终为 600 例）也将包括在内。参与 MEC 其他 GWA 研究的未诊断出 CRC 的西班牙裔人群（n=3,900，U01HG004726，Haiman）将用作对照。我们将使用 Illumina 1M 阵列对所有 3,100 个病例进行基因分型，并使用在 3,900 个对照中收集的可用基因型和流行病学数据。我们的统计分析将包括：单 SNP 和单倍型效应、基因-环境相互作用和 MSI 异质性、肿瘤亚型和 CRC 家族史。我们将使用墨西哥的 CRC 病例和对照（1,000 个病例和 1,000 个对照、欧盟 FP7 资助、CHIBCHA、Carvajal-Carmona/Tomlinson）复制第二阶段的研究结果。我们还将利用 NH-Whites 的 GWA 数据（2,142 例病例，1,909 例对照，U01 CA122839，Casey）（4,000 例病例，6,000 例 NH-White 对照，UK-CHIBCHA，Tomlinson）来检查按种族/种族划分的风险估计的异质性、哥伦比亚人（2,000 例病例和 2,000 例对照，CHIBCHA）、日本人（1,000 个病例和 1,000 个对照）和非裔美国人（1,500 个病例和 1,500 个对照，R01CA126895，Le Marchand）。我们将在几个西班牙裔人群的主要和综合分析中对重复的重要 SNP 进行基因分型（注：由欧盟或 NIH 资助的数据收集研究，但不是 GWAS），包括：800 名波多黎各人、2,000 名巴西人、2,000 名阿根廷人和 3,000 名西班牙/葡萄牙人进行评估研究结果的普遍性。这项研究将通过解决与结直肠癌遗传易感性相关的种族/民族差异的关键问题而产生重大影响，并将通过提供目前缺乏的遗传数据和生物样本资源，促进西班牙裔研究的进一步发展和投资。