# Pilot Project 3: Contribution of Racial Disparity towards the Early Development of Pancreatic Cancer

> **NIH NIH U54** · UNIVERSITY OF FLORIDA · 2020 · $112,953

## Abstract

ABSTRACT: PILOT PROJECT
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most lethal cancer in the USA and is predicted to
become the second most deadly cancer in the country by 2030. Blacks display an overall significantly greater
age adjusted incidence and mortality rate from PDAC compared to Whites. Recognized risk factors for PDAC
while at a higher prevalence in Blacks than Whites, does not account for the increased incidence and mortality
from PDAC in Blacks, suggesting a biological explanation for the observed differences. The process of acinar
ductal metaplasia (ADM) precedes PDAC precursor lesion formation. Since ADM is the earliest known precursor
lesion for PDAC, acinar to ductal transdifferentiation is a key phase in the initiation of pancreatic cancer. We
hypothesize that Blacks undergo ADM to a greater degree than Whites and that genetic as well as epigenetic
factors account for this disparity. Specific Aim 1 will investigate the degree of in vitro ADM quantitatively using
tissue samples from human pancreata of heathy donors obtained from pancreatic islet procurement centers.
Non-islet fractions containing the primary, human pancreatic acini will be cultured and functionality will be
demonstrated by inducing ADM in vitro. The duct formation doubling time and fold change in expression of acinar
and ductal genes between Black and White donors will determine if ADM is enhanced in Blacks. Expression
arrays will be used to identify the top genetic drivers of ADM in Blacks and Whites. Promoter DNA methylation
will determine if epigenetic changes are responsible for the change in gene expression between Blacks and
Whites. Specific Aim 2 will perform a genetic association study to identify SNPs in the genetic drivers of ADM
using nested, case-control cohorts of PDAC data. Successful completion of this project will establish that racial
disparities exist for the ability of pancreatic acini to undergo ADM. We will have also identified a gene expression
signature that will characterize the ADM process by race as well as genetic and epigenetic factors that drive
ADM in Blacks.

## Key facts

- **NIH application ID:** 10006214
- **Project number:** 5U54CA233444-03
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** THOMAS D. SCHMITTGEN
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $112,953
- **Award type:** 5
- **Project period:** 2018-09-17 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10006214

## Citation

> US National Institutes of Health, RePORTER application 10006214, Pilot Project 3: Contribution of Racial Disparity towards the Early Development of Pancreatic Cancer (5U54CA233444-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10006214. Licensed CC0.

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