# Pilot Research Project   Epigenetic Factors and the Microbiome in Disparities in Colon Cancer Outcomes

> **NIH NIH U54** · HUNTER COLLEGE · 2020 · $21,112

## Abstract

PROJECT SUMMARY
Pilot Research Project
Epigenetic Factors and the Microbiome in Disparities in Colon Cancer Outcomes
TUFCCC: Jean-Pierre Issa, MD and Carmen Sapienza, PhD (Co-Leaders)
 HC: Frida Kleiman, PhD (Co-Leader)
Epidemiological data have demonstrated race and/or ethnicity differences in age-adjusted mortality for cancer,
overall, and for the incidence and mortality rates of individual cancers. There are likely multiple reasons for
such disparities, including socioeconomic factors (SES), such as education, access to healthcare, application
of early detection methods and availability of advanced therapies. However, racial disparities in colorectal
cancer provide one indication that biology-based factors are also likely to be at play. Not only are colorectal
cancer mortality rates for African American men and African American women higher than for Caucasian men
and women but African American patients appear less likely to develop microsatellite instable cancers (a type
of cancer with improved outcomes) and tumors from African American patients appear to have a distinct
mutation profile. Our hypothesis is that much of the racial disparity between African Americans and
Caucasians in colon cancer incidence and outcomes are due to environmental and/or genetic differences
between the two groups. This hypothesis is based on published data from our laboratories as well others,
including the identification of DNA methylation differences in the normal colon mucosa of cancer patients that
distinguish cancer patients from patients without cancer with high sensitivity and specificity. The methylation
differences we identified occur in genes in which cancer-associated genetic and epigenetic changes have been
identified but also include genes involved in the metabolism of lipids and carbohydrates, consistent with the
notion that dietary factors influence risk for colon cancer. In addition, our more recent data identifies cancer-
associated alterations to the gut microbiome, including increases in pathogenic species associated with
inflammation. In this application, we will perform analyses that are exactly parallel to our previously published
analyses and to our very strong preliminary data to test the hypothesis that the racial disparities in colon
cancer are driven by race-associated environmental and genetic differences in the normal mucosa that
interact with the gut microbiome to alter cancer risk. We will compare the DNA methylome of normal colon
mucosa of cancer patients and patients without cancer in a race-stratified way to identify a cancer normal colon
“field-effect” signature that is race-associated and determine whether this signature is associated with
chromatin changes that affect gene expression. We will also identify any microbiome components that are
cancer-enriched and race associated. This study will serve as the exploratory groundwork for more
mechanistic studies that will target the genetic and epigenetic pathways identified as race-a...

## Key facts

- **NIH application ID:** 10018487
- **Project number:** 5U54CA221704-03
- **Recipient organization:** HUNTER COLLEGE
- **Principal Investigator:** FRIDA E KLEIMAN
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $21,112
- **Award type:** 5
- **Project period:** 2018-09-18 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018487

## Citation

> US National Institutes of Health, RePORTER application 10018487, Pilot Research Project   Epigenetic Factors and the Microbiome in Disparities in Colon Cancer Outcomes (5U54CA221704-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10018487. Licensed CC0.

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