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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）：现在已经充分认识到，与其他种族/族裔群体相比，非洲裔美国人经历了不成比例的绝经前乳腺癌负担和更高的死亡率。最近的研究表明，非洲裔美国人更有可能患上三阴性乳腺癌（TNBC）或基底样乳腺癌。我们最近发现，西非土著人，非洲裔美国人的创始人人口，TNBC的比例甚至高于非洲裔美国人。我们在尼日利亚乳腺癌研究（NBCS）的第一阶段招募了1233例乳腺癌病例和1101例对照，另外招募了1500例病例和种族和年龄匹配的1500例对照。此外，我们正在进行一项非洲女性乳腺癌全基因组关联研究（GWAS），以研究乳腺癌的常见变异，结果将于2011年秋季公布。在这里，我们提出了一种高通量的全基因组DNA测序和计算生物学方法来检查乳腺癌的罕见，中度突变变异，并扩展了乳腺癌基因组中种族多样性的分析。我们的具体目标是：1）对来自200个良好表型分型病例和200个对照的正常血液和匹配的原发性乳腺肿瘤的基因组（WGS）进行全测序，以鉴定三阴性乳腺癌的生殖系和体细胞变体。我们将通过比较肿瘤中鉴定的变体与配对的正常血液样品和健康对照来区分遗传性变体和体细胞变体，以评估遗传性变体的病因学作用; 2）在>5000例乳腺癌病例和>5000例非洲和非非洲血统对照中筛选选定的基因/变体。我们将首先将通过全基因组测序鉴定的罕见基因型插补到所有GWAS样本中，以进行计算机模拟复制。然后，我们将在非裔美国人乳腺癌联盟中进行复制，其中包括黑人妇女健康研究和三阴性乳腺癌联盟。我们访问其他联盟，包括BCAC，CIMBA和Post GWAS U19将提供其他队列用于复制我们的研究。这种综合方法将增加我们在一个研究不足但独特的人群中识别罕见遗传变异与最具侵袭性的乳腺癌之间的关联的能力。在其他人群中复制我们的研究结果和我们的数据共享计划将通过利用基因组学和生物技术来改善全球健康公平性和减少健康差距，从而带来巨大的公共卫生利益。