The DARC side of Breast Cancer Disparities - African Ancestry and Cancer- Related Immune Response

DARC 方面乳腺癌差异 - 非洲血统和癌症相关免疫反应

基本信息

  • 批准号:
    10835674
  • 负责人:
  • 金额:
    $ 46.84万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-09-23 至 2026-08-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY (tech abs) Even with the typical delays in diagnosis, more advanced stage distribution at diagnosis, and inadequate multidisciplinary breast cancer treatment, these combined factors do not completely explain disparities in breast cancer mortality outcomes, which persist after controlling for stage at diagnosis – and have been so for the past 50 years. The approximately two-fold increased risk of TNBC in AA women has been confirmed by population-based incidence rates regionally as well as nationally and across all age intervals. Compared to non-TNBC, triple negative disease has been confirmed to be an adverse prognostic feature in AA patients, driving some of the mortality disparities. We hypothesize that altered mechanisms of tumor immune responses, which underlies TNBC tumor biology differences between SRR, are caused by population-private genetic variants among individuals with shared west African ancestry. These evolutionarily selected variants alter immune cell behavior and inflammatory mechanisms, leading to novel tumor-immune cell types and significant differences in leukocyte infiltration patterns, which may be associated with poor outcomes. We will perform an innovative multiomics investigation of African-specific gene expression in TNBC, linked to immunological tumor phenotypes. We will harness the novelty of rarely-investigated breast cancer patient populations from diverse African regions with TNBC cases from g admixed populations (i.e. African-American and Afro-Caribbean). The most impactful innovation of this study is the characterization of differential gene expression, coupled with integrated proteomics data, to identify novel tumor phenotypes that are shared among women of the African diaspora. This work will be transformative to our understanding of tumor heterogeneity and biological diversity across patient groups. We propose the follow aims: 1- Determine the ancestry- associated differential gene expression profiles of immune and inflammatory-related genes in primary tumors across an African-enriched cohort of 400 clinically annotated TNBC cases, to immune profiles linked to shared west African genetic ancestry. 2- Characterize ancestry-associated differences in pathological tumor immune response characteristics, including differences in tumor inflammation and/or tumor infiltration of specific immune cell types. 3-Create an African-enriched panel of ex vivo models to validate/investigate the ancestry-associated drivers of altered genetic pathways and immune responses. By completing these aims we expect to yield an African-enriched set of population-private, validated eQTLs, associated with TNBC immune response mechanisms that can be further interrogated by our authenticated ex vivo models.
项目总结(技术abs)

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Breast cancer disparities in outcomes; unmasking biological determinants associated with racial and genetic diversity.
  • DOI:
    10.1007/s10585-021-10087-x
  • 发表时间:
    2022-03
  • 期刊:
  • 影响因子:
    4
  • 作者:
    Martini, Rachel;Newman, Lisa;Davis, Melissa
  • 通讯作者:
    Davis, Melissa
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Melissa B Davis其他文献

Recent advances in Drosophila genomics
  • DOI:
    10.1186/gb-2004-5-8-339
  • 发表时间:
    2004-01-01
  • 期刊:
  • 影响因子:
    9.400
  • 作者:
    Melissa B Davis;Kevin P White
  • 通讯作者:
    Kevin P White

Melissa B Davis的其他文献

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{{ truncateString('Melissa B Davis', 18)}}的其他基金

The DARC side of Breast Cancer Disparities - African Ancestry and Cancer- Related Immune Response
DARC 方面乳腺癌差异 - 非洲血统和癌症相关免疫反应
  • 批准号:
    10198536
  • 财政年份:
    2021
  • 资助金额:
    $ 46.84万
  • 项目类别:
The DARC side of Breast Cancer Disparities - African Ancestry and Cancer- Related Immune Response
DARC 方面乳腺癌差异 - 非洲血统和癌症相关免疫反应
  • 批准号:
    10493136
  • 财政年份:
    2021
  • 资助金额:
    $ 46.84万
  • 项目类别:
5th Annual International Symposium: Improving Breast Cancer Management and Outcomes
第五届年度国际研讨会:改善乳腺癌管理和结果
  • 批准号:
    10237622
  • 财政年份:
    2021
  • 资助金额:
    $ 46.84万
  • 项目类别:
The DARC side of Breast Cancer
乳腺癌的 DARC 方面
  • 批准号:
    9301144
  • 财政年份:
    2017
  • 资助金额:
    $ 46.84万
  • 项目类别:
Genome-wide Detection of Cell-specific Ecdysone Targets
细胞特异性蜕皮激素靶标的全基因组检测
  • 批准号:
    6937471
  • 财政年份:
    2005
  • 资助金额:
    $ 46.84万
  • 项目类别:
Genome-wide Detection of Cell-specific Ecdysone Targets
细胞特异性蜕皮激素靶标的全基因组检测
  • 批准号:
    7053328
  • 财政年份:
    2005
  • 资助金额:
    $ 46.84万
  • 项目类别:
ECDYSONE RECEPTOR REQUIREMENTS IN DROSOPHILA DEVELOPMENT
果蝇发育中的蜕皮激素受体需求
  • 批准号:
    6476351
  • 财政年份:
    2001
  • 资助金额:
    $ 46.84万
  • 项目类别:
ECDYSONE RECEPTOR REQUIREMENTS IN DROSOPHILA DEVELOPMENT
果蝇发育中的蜕皮激素受体需求
  • 批准号:
    6329595
  • 财政年份:
    2000
  • 资助金额:
    $ 46.84万
  • 项目类别:
ECDYSONE RECEPTOR REQUIREMENTS IN DROSOPHILA DEVELOPMENT
果蝇发育中的蜕皮激素受体需求
  • 批准号:
    6012990
  • 财政年份:
    1999
  • 资助金额:
    $ 46.84万
  • 项目类别:

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