Translational Research Program in Cancer Differences across Populations (TRPCDP)

Colorectal cancer (CRC) remains a leading cause of cancer death in the United States, with substantial differences in incidence and mortality rates across population groups. Colorectal cancer etiology is multi-dimensional and is influenced by diet, lifestyle factors, medical history, gut microbiome, and genetics. However, research to understand the biological bases for CRC differences in incidence and mortality have only been done to a limited extend.

The Translational Research Program in Cancer Differences across Populations (TRPCDP) will conduct innovative research focused on developing clinically impactful strategies to understand and address cancer differences across the US, with particular emphasis on colorectal cancer. Our overarching goal is to reduce morbidity and mortality by addressing critical knowledge gaps:

• Enhancement of risk-stratified screening and early detection across genetic ancestral groups to inform primary prevention strategies
• Molecular and microbial characterization of colorectal cancer across populations
• Identification of high-risk patients who could benefit from intensified surveillance or additional treatment modalities
• Discovery and validation of novel molecular/biological markers related to lethal disease risk that may serve as therapeutic targets
  

Program Foundation and Resources

During the P20 phase, we assembled a comprehensive biorepository containing varied biospecimen types and detailed clinical data from different CRC patient populations. Combined with our established leadership in genetic epidemiology, we have access to the world's largest CRC germline genetic dataset spanning multiple genetic ancestries. Building upon these unique resources, our P50 program will implement four translational research projects supported by three essential cores, along with robust Career Enhancement Program (CEP) and Developmental Research Program (DRP) components.

Specific Aims

Aim 1: Improve risk-stratified screening and early detection across genetic ancestral groups. We will develop clinically actionable risk prediction models that perform consistently across population groups and inform primary prevention strategy selection (SPORE Project 1).

Aim 2: Reduce differences in CRC-specific mortality. We will discover and validate novel molecular and biological markers associated with lethal CRC risk and treatment response to guide surveillance strategies and treatment selection for CRC survivors (SPORE Projects 2 and 3).

Aim 3: Discover novel therapeutic targets and test clinical interventions to reduce CRC mortality. We will elucidate the genetic, molecular, and microbial characteristics that distinguish CRC across different populations, leading to targeted therapeutic strategy development. We will evaluate intervention effectiveness through rigorous clinical trials (SPORE Projects 1, 2, 3, and 4).

Multi-Institutional Collaboration

This research effort leverages strong collaborative partnerships across leading institutions:

• Alaska Native Tribal Health Consortium, Alaska
• Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, California
• Fred Hutch, Washington
• Ochsner Clinical Foundation, Louisiana