Replication Study of Breast Cancer Susceptibility Genes in Blacks

黑人乳腺癌易感基因的复制研究

基本信息

批准号：
8100727
负责人：
Dezheng Huo
金额：
$ 10万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-21 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8100727
关键词：
10q21 16q12 2q35 6q22 Affect Africa African African American Age Barbados Breast Breast Cancer Risk Factor Breast Cancer Treatment Cancer-Predisposing Gene Case-Control Studies Caucasians Caucasoid Race Chicago Chromosomes Clinical DNA Data Databases Development Disease Early Diagnosis Enrollment Environmental Exposure Environmental Risk Factor Epidemiology Ethnic group European FGFR2 gene Funding Future Genes Genetic Genetic Risk Genome Genomics Genotype Health Services Accessibility Incidence Individual Joints Lead Life Linkage Disequilibrium Logistic Regressions Malignant Neoplasms Maps Modification Mutation National Human Genome Research Institute Native-Born Negative Finding Nigeria Odds Ratio Pattern Play Population Population Attributable Risks Population Control Predisposition Prevalence Prevention Prevention strategy Procedures Recruitment Activity Reproduction spores Risk Risk Assessment Risk Factors Role Sampling Single Nucleotide Polymorphism Staging Stratification Surrogate Markers Testing Translating Update Variant Woman base breast cancer family registry cancer risk clinically significant cohort early onset epidemiologic data experience gene environment interaction genetic epidemiology genetic risk factor genetic variant genome wide association study health disparity innovation interest malignant breast neoplasm minority health mortality novel racial and ethnic

项目摘要

DESCRIPTION (provided by applicant): African Americans and Africans experience a disproportionate burden of aggressive breast cancer in comparison to all other racial/ethnic groups for reasons that remain unknown and understudied. The paucity of data on the genetic epidemiology of breast cancer for women of African ancestry hinders the development of innovative prevention to reduce health disparities. Because common genetic variants with potential large population attributable risk may play a role in breast cancer development and progression for women of African ancestry in a way different from women of European ancestry, we propose to replicate 5 novel breast cancer susceptibility loci (involving 11 genes) previously identified in genome-wide association studies in a well-characterized cohort of about 2200 breast cancer cases and 2300 controls, all of African ancestry. DNA samples and epidemiologic data for this large study have been collected through Nigerian Breast Cancer Study (Africans), Barbados National Cancer Study (African Barbadians), and the Chicago Breast SPORE and the Breast Cancer Family Registry (African Americans). We will employ the replication plus fine-mapping strategy to genotype exactly same SNPs identified in original studies and a panel of tagSNPs and putative functional variants in these 5 genomic regions. For African Americans, ancestry informative markers will also be genotyped to control for population stratification. Multiple imputation procedure will be used to impute variants that are not genotyped. Logistic regressions will be used to test the associations and calculate odd ratios. Furthermore, we will examine gene-environment interaction as there are sharp contrasts in epidemiologic risk factors among the three populations of African ancestry. This study will advance understanding the genetic risk factors for breast cancer in women of African descent and will be invaluable in developing novel prevention strategies in the future.

描述（由申请人提供）：与所有其他种族/族裔相比，非洲裔美国人和非洲人的侵略性乳腺癌负担不成比例，原因是未知和研究的原因。非洲血统妇女乳腺癌遗传流行病学的数据匮乏阻碍了预防创新的预防，以减少健康差异。由于具有潜在人口众多风险的常见遗传变异可能在非洲血统的妇女的乳腺癌发展和与欧洲血统的妇女不同的方式中起作用，因此我们建议复制5个新的乳腺癌易感性基因座（涉及11个基因）（涉及11个基因），在基因组范围内在基因组范围内鉴定出的，在基因组范围内的研究中，在一个良好的培训群体中，大约2200个乳腺癌和2300个乳腺癌和2300个乳腺癌且均为2300群体。这项大型研究的DNA样品和流行病学数据已通过尼日利亚乳腺癌研究（非洲人），巴巴多斯国家癌症研究（非洲巴巴多人）和芝加哥乳腺孢子和乳腺癌家庭登记局（非裔美国人）收集。在这5个基因组区域中，我们将采用复制加上精细映射策略以及在原始研究中确定的完全相同的基因型SNP和一组TAGSNP和推定功能变体。对于非洲裔美国人，还将为祖先提供信息标记，以控制人口分层。多个插补程序将用于估算未进行基因分型的变体。逻辑回归将用于测试关联并计算奇数比。此外，我们将检查基因环境的相互作用，因为非洲血统的三个人群中流行病学危险因素存在鲜明的对比。这项研究将促进了解非洲血统女性乳腺癌的遗传危险因素，并将在未来制定新型预防策略方面无价。