# Colonic responses to vitamin D and aspirin in African- and European-Americans

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2022 · $363,486

## Abstract

PROJECT SUMMARY/ABSTRACT
 African Americans (AA) have the greatest burden of colorectal cancer (CRC) in the US, and biological
reasons for this disparity remain incompletely understood. Interactions between host and environmental
factors, including chemopreventive treatments, are known to modify CRC risk, and there is emerging evidence
of differences in treatment effects between AA and European Americans (EA) for the two most promising
chemopreventive agents, vitamin D and aspirin. Our broad objective is to model and understand how inter-
ethnic differences in treatment responses could contribute to CRC disparities. Our laboratory has optimized
stem cell-derived human organoid cultures to study cellular responses between individuals that have not been
feasible using traditional models. In this proposal, we use colonic organoids to test the central hypothesis that
transcriptional, chromatin accessibility and cellular responses to vitamin D and/or aspirin differ between AA and
EA, and that these inter-ethnic differences could impact CRC risk and clinical treatment response.
 We previously treated ex vivo primary colon tissue from AA and EA with active vitamin D (1,25D) and
identified several genes with inter-ethnic response differences. The success of finding genes with inter-ethnic
response differences provides rationale for extending our genome-wide approach to 1,25D, aspirin and
combination treatments in a larger sample size of colonic organoids (80 AA & 80 EA) to achieve greater power
to identify inter-ethnic differences in transcriptional networks as well as chromatin accessibility. We will
replicate observed differences in an independent cohort of organoids as well as test for cancer-relevant cellular
treatment phenotypes in a subset of treated organoids (50 AA & 50 EA) (Aim 1). Further, using RNA-seq data
obtained in Aim 1, we will test for a genetic contribution to response differences between individuals and
ethnicities using allele specific expression. The response genes and SNPs identified will be tested for
enrichment among genes and SNPs from NIH-funded CRC GWAS and chemoprevention trials as well as
tested mechanistically using functional assays (Aim 2).
 The outcomes of our innovative study will: i) elucidate underlying biology and genetic architecture of
responses to vitamin D and aspirin in the colon and how they differ by ethnicity, ii) connect cellular response
with CRC risk and response to chemoprevention, and iii) identify genes and SNPs for mechanistic studies as
well as for possible development as novel biomarkers for personalized CRC prevention in order to, ultimately,
reduce CRC disparities.

## Key facts

- **NIH application ID:** 10439767
- **Project number:** 5R01CA220329-05
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Sonia Kupfer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $363,486
- **Award type:** 5
- **Project period:** 2018-07-03 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439767

## Citation

> US National Institutes of Health, RePORTER application 10439767, Colonic responses to vitamin D and aspirin in African- and European-Americans (5R01CA220329-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10439767. Licensed CC0.

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