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

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $517,362

## Abstract

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.

## Key facts

- **NIH application ID:** 10198536
- **Project number:** 1R01CA259396-01
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Melissa B Davis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $517,362
- **Award type:** 1
- **Project period:** 2021-09-23 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198536

## Citation

> US National Institutes of Health, RePORTER application 10198536, The DARC side of Breast Cancer Disparities - African Ancestry and Cancer- Related Immune Response (1R01CA259396-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10198536. Licensed CC0.

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