# Mitochondrial dysfunction and chronic stress intersect as mechanisms driving breast cancer racial disparities

> **NIH NIH R21** · VIRGINIA COMMONWEALTH UNIVERSITY · 2022 · $217,738

## Abstract

Project Summary/Abstract PI: Shock, Lisa S.
Breast cancer represents an estimated 30% of all new cancer diagnoses in women and claimed over 40,000
lives in 2020 alone (1). African American (AA) women are disproportionately affected; AA women are more
likely to develop aggressive triple-negative subtypes, and suffer from recurrent or metastatic disease (2-4), and
mortality rates among AA breast cancer patients remain highest compared to all other race/ethnicity groups (2-
5). The biological and non-biological factors underlying these disparities are complex and largely unknown.
Allostatic load (AL) is an effective measure of physiologic dysregulation secondary to stress and is often used
to quantify the physiological burden of breast cancer (10-13). AL has been shown to be positively associated
with breast cancer risk and more aggressive phenotypes among AA women, but not among white women
(10,12-14). These findings support the notion that social and biological factors contribute to breast cancer
features and survival. Mitochondrial DNA (mtDNA) abnormalities including mutations, deletions, and copy
number changes, are frequent events in cancer. A recent pan-cancer study found that tumors from AA patients
were enriched for mitochondrial OXPHOS and contained more mitochondria than the same cancers from white
Americans (15). Increased mitochondrial DNA (mtDNA) copy number in the blood of breast cancer patients
was recently shown to be positively associated with AL, suggesting that mtDNA content is a possible mediator
linking higher AL and aggressive breast tumor characteristics (10). MtDNA is epigenetically modified by
cytosine and adenine methylation, and this represents a powerful mechanism for environmental regulation of
mitochondrial function (Fig 1, 16-19). While genome-wide DNA methylation changes have been linked to
breast tumor characteristics, the role of mtDNA methylation in breast cancer incidence/mortality remains
unexplored. The studies proposed here aim to better understand the social and biological basis for why
black women are disproportionately affected by more severe breast cancer subtypes and higher
mortality rates. Epidemiological, molecular and metabonomic approaches are proposed to examine the
effects of chronic stress on mitochondrial biology as they contribute to breast cancer disparities. First, we will
investigate the impact of AL on mitochondrial biology in breast tumor tissues from both AA and white patients.
We will determine the extent to which AL is associated with mitochondrial abnormalities, including mtDNA
mutations/deletions, copy number, epigenetic modifications and mitochondrial enzyme defects. Second, we will
evaluate the effects of stress hormones on mitochondrial function in a panel of breast cancer and normal cell
lines cultured in 2- and 3-dimensions. Stress-induced changes to mtDNA content, epigenetic modification and
metabolic changes will be quantified. These approaches will explore the interplay between p...

## Key facts

- **NIH application ID:** 10527841
- **Project number:** 1R21CA267975-01A1
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Lisa Sale Shock
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $217,738
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527841

## Citation

> US National Institutes of Health, RePORTER application 10527841, Mitochondrial dysfunction and chronic stress intersect as mechanisms driving breast cancer racial disparities (1R21CA267975-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10527841. Licensed CC0.

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