# Kansas Center for Metabolism and Obesity REsearch (KC-MORE)

> **NIH NIH P20** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2024 · $280,142

## Abstract

ABSTRACT
Obesity is a leading cause of health disparities in the general population, being associated with increased risk of
breast cancer, decreased response to treatment and higher rates of cancer-associated mortality. Women with a
germline mutation in BRCA1 or BRCA2 have a 4-7-times increased risk of developing breast cancer compared
to the general population. We have discovered that body mass index (BMI) and poor metabolic health is
associated with more DNA damage in the non-tumor breast glands of BRCA1 and BRCA2 mutation carriers.
DNA damage is credited for the development of cancer from non-cancer cells. In fact, our studies in mice
demonstrate that more mice develop tumors when they are obese (compared to lean) and that these develop at
a younger age. We now have evidence that having a mutation in BRCA may predispose to poor metabolic health,
leading to a potential vicious cycle whereby increased cancer risk may be in part driven by detrimental effects of
BRCA mutations in metabolic tissues, including the liver, adipose tissue, pancreas and muscle.
We hypothesize that carrying a BRCA mutation leads to defects in mitochondria, the powerhouse of the cell, in
metabolic tissues, leading to poor metabolic health and increased cancer risk.
This study aims to:
 1) Understand the mechanism of impaired metabolic health in mice with loss of Brca1
 2) Determine if carrying a mutation in BRCA affects biomarkers of metabolic health in women
These studies will determine whether additional follow up related to metabolic health should be considered after
a BRCA diagnosis. By also exploring metabolic targets, this project has the potential to identify risk reduction
strategies for BRCA mutation carriers for whom standard of care remains prophylactic surgery.

## Key facts

- **NIH application ID:** 10952036
- **Project number:** 3P20GM144269-03S1
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** John P Thyfault
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $280,142
- **Award type:** 3
- **Project period:** 2022-04-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10952036

## Citation

> US National Institutes of Health, RePORTER application 10952036, Kansas Center for Metabolism and Obesity REsearch (KC-MORE) (3P20GM144269-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10952036. Licensed CC0.

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