Using Genomics to Reduce Breast Cancer Disparities in the African Diaspora

利用基因组学减少非洲侨民的乳腺癌差异

基本信息

批准号：
8513943
负责人：
Dezheng Huo
金额：
$ 69.96万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-19 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8513943
关键词：
Accounting African African American Age Alcohol consumption Alleles Antioxidants Bilirubin Bioinformatics Biological Markers Biotechnology Blood Blood specimen Cancer Etiology Chronic Communities Complex Computational Biology Computer Simulation Cultural Backgrounds DNA Sequence Data Data Storage and Retrieval Environmental Risk Factor Epidemiology Ethnic Origin Ethnic group Etiology Founder Generation Genes Genetic Genetic Variation Genome Genomics Genotype Health Health Benefit Heterogeneity Hormones Indigenous Inflammation Inherited Knowledge Mammary Neoplasms Measures Medical History Modeling Molecular Target Mutation Neighborhoods Outcome Penetrance Persons Phase Phenotype Physical activity Plasma Play Population Premenopause Puberty Public Health Radiation Recording of previous events Recruitment Activity Research Infrastructure Resources Risk Risk Factors Role Sampling Smoking Somatic Mutation Statistical Models Testing The Cancer Genome Atlas Therapeutic Translating Variant Vitamin D Woman Women&apos s Health Work base cancer genome cancer health disparity cancer risk case control cohort data mining data sharing experience genetic profiling genome sequencing genome wide association study global health health disparity health equity improved insight lifestyle factors malignant breast neoplasm mortality novel novel strategies oncology public health relevance racial and ethnic racial/ethnic difference reproductive triple-negative invasive breast carcinoma tumor tumor progression young woman

项目摘要

DESCRIPTION (provided by applicant): It is now well recognized that African Americans experience a disproportionate burden of pre-menopausal breast cancer and higher mortality rates in comparison to other racial/ethnic groups. Recent studies demonstrate that African Americans are more likely to develop triple-negative breast cancer (TNBC) or basal- like breast cancer in particular. We recently showed that indigenous West Africans, the founder population of African Americans had even higher proportions of TNBC than do African Americans. We have recruited 1233 breast cancer cases and 1101 controls in Phase 1 of the Nigerian Breast Cancer Study (NBCS) and recruitment of additional 1500 cases and ethnicity & age-matched 1500 controls is ongoing. In addition, we are conducting a genome-wide association study (GWAS) of breast cancer in women of African Ancestry to study common variants for breast cancer and results will be available in autumn 2011. Here, we propose a high- throughput whole genome DNA sequencing and computational biology approach to examine rare, moderate- penetrance variants for breast cancers and expand the analysis of ethnic diversity in breast cancer genomes. Our specific aims are to: 1) fully sequence genomes (WGS) of normal blood and matched primary breast tumors from 200 well-phenotyped cases and 200 controls to identify germline and somatic variants for triple negative breast cancer. We will distinguish inherited from somatic variants by comparing variants identified in tumors with the paired normal blood samples and the healthy controls to evaluate the etiologic effect of the inherited variants; 2) Validate selected genes/variants in >5000 breast cancer cases and >5000 controls of African and non-African ancestry. We will first impute rare genotypes identified by whole genome sequencing into all the GWAS samples to conduct an in silico replication. Then, we will perform replication in the African American Breast Cancer Consortium, which includes Black Women's Health Study and the Triple Negative Breast Cancer Consortium. Our access to other Consortia including BCAC, CIMBA and Post GWAS U19 will provide other cohorts for replicating our studies. This integrative approach will increase our power to identify associations between rare inherited variants and the most aggressive form of breast cancer in an understudied but unique population. The replication of our study findings in other populations and our data sharing plans will bring enormous public health benefit by harnessing genomics and biotechnology to improve global health equity and reduce health disparities.

描述（由申请人提供）：与其他种族/族裔相比，非洲裔美国人的绝经前乳腺癌和更高的死亡率负担不成比例。最近的研究表明，非洲裔美国人更有可能发展三阴性乳腺癌（TNBC）或基础乳腺癌。我们最近表明，西非土著人，非裔美国人的创始人人口的TNBC比例甚至比非洲裔美国人更高。我们已经在尼日利亚乳腺癌研究（NBC）的第1阶段招募了1233例乳腺癌病例和1101例对照，并正在招募其他1500例，种族和年龄匹配的1500个控制正在进行中。此外，我们正在对非洲祖先女性进行全基因组乳腺癌研究（GWAS）研究，以研究乳腺癌的常见变体，结果将于2011年秋季提供。在这里，我们建议一种高吞吐量的整个基因组DNA测序和计算生物学方法，以检查罕见的，中度的，适度的乳腺渗透性变体，用于乳腺癌的乳腺癌和癌症分析癌症的多样性。我们的具体目的是：1）正常血液的完全序列基因组（WGS），并匹配来自200例良好型病例的原发性乳腺肿瘤和200个对照，以鉴定三乳乳腺癌的生殖线和躯体变异。我们将通过比较在肿瘤中鉴定出的变体和配对的正常血液样本和健康对照以评估遗传变体的病因效应，从而区分遗传性变体。 2）验证> 5000例乳腺癌病例和> 5000个非洲和非非洲血统的控制基因/变体。我们将首先将整个基因组测序鉴定的稀有基因型估算为所有GWAS样品，以进行计算机复制。然后，我们将在非裔美国乳腺癌财团中进行复制，其中包括黑人妇女的健康研究和三重阴性乳腺癌联盟。我们进入包括BCAC，CIMBA和GWAS Post U19在内的其他财团的访问将为复制我们的研究提供其他同类。这种综合方法将增加我们确定稀有遗传变体与最具侵略性的乳腺癌形式之间的关联的力量。在其他人群中的研究结果以及我们的数据共享计划的复制将通过利用基因组学和生物技术来改善全球健康公平并降低健康差异来带来巨大的公共卫生益处。