# Colorectal cancer risk factors, risk prediction and blood-based biomarker by tumor consensus molecular subtype

> **NIH NIH U01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $392,221

## Abstract

PLCO Project Summary
Despite the availability of effective screening techniques, only 40% of colorectal cancer (CRC) cases are
diagnosed at a localized stage of disease. This is likely due to a combination of factors, including screening non-
compliance, limitations in the screening sensitivity and specificity, and heterogeneity of CRC biology. Specifically
the existence of more aggressive tumor subtypes, which may have a shorter natural history, combined with
screening inadequacies hinder our ability to detect more early stage disease and further reduce CRC morbidity
and mortality.
 The recently described consensus molecular subtypes (CMS) of CRC include a more aggressive,
mesenchymal subtype and provide a framework for stratified risk assessment, screening recommendations and
prevention interventions. The four subtypes identified have distinct biology and clinical outcomes, suggesting the
possibility of unique risk factors, prevention, and screening strategies. Specifically, CMS1 (Immune, 14% of
cases) is associated with high micro-satellite instability (MSI), BRAF mutations and immune infiltration, CMS2
(Canonical, 37%) accounts for the largest percent of tumors and is characterized by activation of WNT and MYC,
CMS3 (Metabolic, 13%) is characterized by low somatic copy number alterations, KRAS mutations and tumor
metabolic dysregulation, CMS4 (Mesenchymal, 23%) is characterized by stromal infiltration, TGF-β activation,
angiogenesis and worse overall and relapse-free survival (Nat Med. 2015, 21:1350). The studies in this proposal
utilize the CMS framework to develop and test a risk-prediction tool and test the CMS-specific performance of a
validated blood-based three-marker panel.
 Building on our preliminary data and using the high-quality, longitudinal data and tumor RNA from the
Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we plan to test the associations of CMS with
age, smoking status, and tumor stage at diagnosis (Aim 1). Using the associations from aim 1, we plan to build
and test a CMS-specific CRC risk prediction tool to facilitate screening and prevention efforts (Aim 2). We also
plan to further test the performance of our validated blood-based three-marker panel across CMS and in the
years prior to diagnosis (Aim 3).
 The combination of a CMS-specific risk prediction tool and a validated blood-based biomarker has the
potential to greatly improve CRC screening compliance and early detection, leading to a reduction in morbidity
and mortality from CRC.

## Key facts

- **NIH application ID:** 10021547
- **Project number:** 5U01CA222163-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** ROBERT S BRESALIER
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $392,221
- **Award type:** 5
- **Project period:** 2019-09-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10021547

## Citation

> US National Institutes of Health, RePORTER application 10021547, Colorectal cancer risk factors, risk prediction and blood-based biomarker by tumor consensus molecular subtype (5U01CA222163-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10021547. Licensed CC0.

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