Translational Research Program in Colorectal Cancer Disparities (TRPCD)
Fred Hutchinson Cancer Research Center
Principal Investigator(s):
Ulrike Peters, PhD, MPH
Christopher Li, MD, PhD
Timothy Thomas, MD
- Principal Investigator(s) Contact Information
- Overview
- Project 1: Discovery of novel tumor-tissue based predictors of colorectal cancer mortality by race/ethnicity
- Project 2: The colorectal cancer -associated microbiome: Racial/ethnic differences, impact on tumor microenvironment and mortality
- Administrative Core
- Biospecimen and Pathology Core
- Developmental Research Program
- Career Enhancement Program
Principal Investigator(s) Contact Information
Ulrike Peters, PhD, MPH
Professor, Associate Director, Endowed Chair
Public Health Sciences Division
Fred Hutchinson Cancer Research Center
1100 Fairview Ave N, M4-B402
Seattle, WA 98109
(206) 667-2450
Christopher Li, MD, PhD
Professor
Public Health Sciences Division
Faculty Director, Diversity, Equity and Inclusion
Fred Hutchinson Cancer Research Center
1100 Fairview Ave N, M4-C308
Seattle, WA 98109
(206) 667-5948
Timothy Thomas, MD
Division Director, Clinical & Research Services Department In The of Community Health Services
Alaska Native Tribal Health Consortium
4000 Ambassador Dr
Anchorage, AK 99508
Overview
The Fred Hutchinson Cancer Research Center Translational Research Program in Colorectal Cancer Disparities (TRPCD) was specifically developed to address disparities in colorectal cancer incidence (CRC) and mortality in the United States, which are higher among Alaska Native and African American populations.
Our Program includes two translational research projects.
- Project 1: Discovery of novel tumor-tissue based predictors of CRC mortality by race/ethnicity
- Project 2: The CRC-associated microbiome: Racial and ethnic differences and similarities, impact on tumor microenvironment, and mortality
These projects are supported by two shared resources: The Pathology and Biospecimen Core and the Administration Core. The TRPCD also supports a Developmental Research Program to support innovative translational research.
Project 1: Discovery of novel tumor-tissue based predictors of colorectal cancer mortality by race/ethnicity
Project Co-Leaders:
Christopher Li, MD, PhD
William Grady, MD
Previous studies demonstrated important differences in the molecular features of colorectal cancer among different racial and ethnic groups. However, these studies almost exclusively focused on African American versus non-Hispanic white comparisons and have generally been limited by small sample sizes. Some of these differences may be clinically actionable. For example, African American colorectal cancer patients more frequently have PIK3CA mutations compared with non-Hispanic White patients, suggesting that NSAIDs could be particularly beneficial for African American patients. However, despite the persistent disparities in colorectal cancer incidence and mortality rates observed across other racial and ethnic groups, molecular characteristics for other populations are very limited.
The objective of this study is to evaluate molecular differences and similarities in colorectal cancer across four racial/ethnic groups (Alaska Native, African American, Hispanic, and non-Hispanic White) and use these data to: a) investigate their relevance to colorectal cancer epidemiology and prevention; b) identify novel tumor-tissue based predictors of colorectal cancer-specific mortality that could help guide clinical decision making, improve outcomes, and reduce long-standing disparities; and c) discover novel intervention targets that may be particularly relevant to colorectal cancer in specific populations. We are performing RNAseq analysis on RNA extracted from formalin-fixed paraffin embedded (FFPE) tumor blocks.
Project 2: The colorectal cancer -associated microbiome: Racial/ethnic differences, impact on tumor microenvironment and mortality
Project Co-Leaders:
Amanda Phipps, PhD
Susan Bullman, PhD
Ulrike Peters, PhD, MPH
Increasing evidence suggests that enrichment of specific bacteria could play an important role in colorectal cancer initiation and progression. Unbiased genomic analyses have provided strong evidence that Fusobacterium nucleatum is involved in colorectal cancer etiology and progression. Recent studies have also linked other microbiota, such as pks+ Escherichia coli, and enterotoxigenic Bacteroides fragilis, with differing plausible microbial-based mechanisms of action. While promising, studies of these and other bacteria have been primarily conducted among non-Hispanic White patients, thus limiting our understanding as to their relevance and importance to colorectal cancer in other racial and ethnic groups. Given the considerable differences in dietary patterns and environmental exposures across populations, and the known influence of such factors on the gut microbiome, it is plausible that the composition of the tumor-associated microbial community could differ substantially across these groups. However, while racial and ethnic disparities in colorectal cancer burden are clearly recognized, the contribution of the microbiome to these disparities is not understood.
The objective of this study is to use targeted candidate and discovery-based agnostic approaches to identify differences and similarities in the tumor-associated microbiome in colorectal cancer by race and ethnicity (Aim 1), their associations with aspects of the tumor microenvironment (Aim 2), and their impact on colorectal cancer lethality (Aim 3). We are using archival tumor tissue specimens to quantify the abundance of specific oncogenic bacteria via highly sensitive digital droplet PCR (ddPCR); we are also sequencing bacterial 16S rRNA gene segments from tumor tissue specimens and, for a subset of individuals, matched normal tissue specimens. We are utilizing RNAseq data generated on the same subjects in Project 1 to interrogate the tumor-associated bacteria with tumor immune profiles and gene expression patterns.
Administrative Core
Core Directors:
Ulrike Peters, PhD, MPH
Christopher Li, MD, PhD
The Administrative Core facilitates communication and sustains integration among the SPORE members and projects, as well as provides efficient support services for all of the P20 components, in order to maximize synergy in achieving our translational research goals.
Biospecimen and Pathology Core
Core Directors:
Amanda Koehne, DVM, PhD, DACVP
Tabitha Harrison, MPH
Diana Redwood, PhD
The Biospecimen and Pathology Core (BPC) supports Projects 1 and 2, and the Developmental Research Program through organizing and processing specimens contributed by collaborating institutions, as well as by collecting and harmonizing patient clinical data for downstream analyses. The BPC also conducts laboratory analyses and establishes valuable resources for future collaborations by creating tumor microarrays, and banking tumor DNA and RNA.
Developmental Research Program
Program Directors:
Amanda Phipps, PhD
William Grady, MD
The Developmental Research Program (DRP) provides key support to develop novel translational early-phase projects in the area of cancer disparities that, ultimately, will contribute to the reduction in the morbidity and mortality of cancer among medically underserved populations. Through the Career Enhancement Program, operated through the Administrative Core, we aim to advance the career of early-stage investigators, particularly those from underrepresented racial and ethnic backgrounds, and encourage them to apply to the Developmental Research Program. Our goal is to fund Developmental Projects that span a range of translational cancer disparities research, including human molecular biology, epidemiology (primary and secondary prevention), early detection, prognosis, therapeutics, and survivorship.
Career Enhancement Program
Program Directors:
Christopher Li, MD, PhD
Timothy Thomas, MD
The Career Enhancement Program identifies and supports promising junior investigators, and those new to the field of cancer disparities. This is done with a particular emphasis on supporting underrepresented minority scientists.