# Epigenetic age acceleration, neighborhood disadvantage, and racial disparities in risk of colon adenoma

> **NIH NIH P20** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $95,845

## Abstract

Summary
 Racial disparities in colorectal cancer (CRC) have been well documented and are widening. Increasing
data strongly suggest that neighborhood socioeconomic disparities contribute to racial/ethnic health disparities
across a variety of health outcomes above and beyond individual-level risk factors. How neighborhood social
and structural disadvantages may modulate an individual's risk, and the molecular mechanisms by which these
multiple-level risk factors may act upon to drive the development of colon neoplasia are largely unexplored.
We propose an innovative epigenetic epidemiology study to comprehensively examine the complex interplay of
neighborhood-level socioeconomic status, individual-level risk factors, and epigenetic age acceleration of normal
colonic tissues in racial disparities and the development early colon neoplasia. Our central hypothesis is that
colonic tissue epigenetic age acceleration, assessed by genome-wide DNA methylation, mediates the race-
differential colon carcinogenic effects of individual-level CRC risk factors. We further hypothesize that
neighborhood disadvantage in part accounts for racial disparities in the association of known individual-level
CRC risk factors and risk of early colon neoplasia. Our proposal capitalizes upon a unique resource established
as part of the parent Cleveland Colon Screening and Risk Factors Cohort Study where extensive epidemiological
data and normal colonic tissues have been collected from 928 (367 African Americans, 561 Caucasians) patients
(436 adenoma cases and 492 adenoma-free controls) undergoing colon screening. By cross-linking the cohort
to the NEO CANDO (NorthEast Ohio Community and Neighborhood Data for Organizing) database that contains
over 20 years of indicators on social, economic and physical conditions in the region's communities, we will use
various census tract-based neighborhood socioeconomic data to assess neighborhood disadvantage for the
current proposal. We will first examine the effect of race and individual-level risk factors on colon specific
epigenetic age acceleration (Aims 1 and 2). We will then investigate the effect of upstream neighborhood
contextual factors on epigenetic age acceleration above and beyond individual-level risk factors (Aim 3). Last,
we will use a structural equation modeling approach to synthesize the information of neighborhood disadvantage
and individual-level risk factors and evaluate both the direct and indirect (i.e., mediated by epigenetic age
acceleration) effects on risk of colon adenoma (Aim 4). Our study will provide novel insight of how neighborhood
disadvantage and individual lifestyle may accelerate epigenetic aging of colon and drive racial disparities in the
development of early colon neoplasia. Our results will have significant implication for developing effective primary
prevention strategy to reduce racial disparities in colon neoplasia.

## Key facts

- **NIH application ID:** 10469705
- **Project number:** 3P20CA233216-03S1
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Li Li
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $95,845
- **Award type:** 3
- **Project period:** 2018-09-18 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469705

## Citation

> US National Institutes of Health, RePORTER application 10469705, Epigenetic age acceleration, neighborhood disadvantage, and racial disparities in risk of colon adenoma (3P20CA233216-03S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10469705. Licensed CC0.

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