# Pancreatic cancer variant analysis of the All of Us cohort

> **NIH NIH P20** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2022 · $115,125

## Abstract

PROJECT SUMMARY
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that is refractory to current treatment strategies
due in part to adaptive mechanisms of chemoresistance. Racial health disparities also confound the treatment
and care of these patients. Blacks have significantly higher incidence rates of PDAC and decreased survival
times compared to Whites and Latino/Hispanics (L/H) even after socioeconomic status and tumor stages are
controlled. Therefore, it is likely different racial groups exhibit unique molecular characteristics in PDAC tumors
that contribute to these health disparities. The molecular characteristics that distinguish PDAC tumors between
racial groups have the potential to identify novel therapeutic targets required to overcome the disparities. Indeed,
delineating the underlying molecular basis for health disparities in lung, breast and prostate cancers has led to
therapeutic advancements and improved patient outcomes. Similar breakthroughs for PDAC are possible and
needed for this deadly disease, but this field of research has not yet been adequately explored. We identified 4
distinct subtypes of PDAC (Metabolic, Progenitor-like, Proliferative, and Inflammatory) that can be distinguished
using multivariate analysis of quantitative mass spectrometry data. These PDAC subtypes are predictive of
therapeutic response, but this has not yet been analyzed in a racially diverse population. We have examined the
proteomes of primary PDAC tumors using quantitative mass spectrometry and identified unique protein
signatures for Blacks, L/H, and Whites. In PDAC tumors from Black patients, we observed features consistent
with the Inflammatory subtype of PDAC, which is characterized by an inflammatory microenvironment and
resistance to chemotherapy. Therefore, it is possible that race influences subtype and Blacks could preferentially
develop the more aggressive and treatment refractory Inflammatory subtype. However, the underlying genetic
variants associated with PDAC subtype specification have not been examined. Toward this goal, our project will
utilize the All of Us database to identify variants in a diverse cohort pancreatic cancer patients and evaluate
specific gene sets associated with PDAC tumorigenesis, including alcohol responsive genes, and differentially
expressed proteins in PDACs originating in Blacks. In addition, we will perform a discovery GWAS analysis to
identify variants associated with PDAC development in the All of Us cohort and examine their predicted functional
consequences in selected PDAC subtype specification genes. The successful completion of these aims outlined
in this proposal has the potential to improve our understanding of the drivers of PDAC subtype specification,
which could be developed to improve overall patient survival by optimizing treatment strategies.

## Key facts

- **NIH application ID:** 10660291
- **Project number:** 3P20GM121316-05S2
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Robert E. Lewis
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $115,125
- **Award type:** 3
- **Project period:** 2022-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10660291

## Citation

> US National Institutes of Health, RePORTER application 10660291, Pancreatic cancer variant analysis of the All of Us cohort (3P20GM121316-05S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10660291. Licensed CC0.

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