# Mathematical Optimization of Surveillance Ages to Intercept colitis-associated Colorectal cancer (MOSAIC)

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2023 · —

## Abstract

The practical goal of this project is to improve screening and surveillance strategies for Veterans living with
inflammatory bowel disease (IBD) who are at increased risk of developing colorectal cancer. Although the risk
in each individual patient is highly heterogenous, the VA surveillance program currently examines over 90,000
patients with IBD colitis under a fairly rigid “one-size-fits-all” paradigm: recommended colonoscopy every 1-3
years starting with an index screening 8 years after IBD diagnosis with hopes to detect early, treatable colitis-
associated colorectal cancers (CA-CRC) before they are more dangerous. These intervals were based on
minimal evidence because trials are difficult to perform, and they have not changed in over 30 years leading to
thousands of unnecessary colonoscopies performed yearly in Veterans who have incredibly low risk of
developing CA-CRC. Our study will address critical knowledge gaps in this field including 1) inherited genetic
risk of CA-CRC in Veterans, and 2) timescales for cellular evolution that define ideal ‘windows of opportunity’ to
intercept early cancers in IBD. Our team has extensive expertise in building computational tools for assessing
screening and surveillance efficacy, deriving and validating clinical decision support tools for CA-CRC, and
analyzing genomic evolution in IBD colitis. Our study will provide an unprecedented level of molecular detail that
has not been achieved in any previous study of pre-cancer evolution in IBD colitis by leveraging thousands of
genomes collected serially from UK patient cohorts. We will focus on risk prediction for patients with IBD colitis
within the Million Veteran Program (MVP) and tailor risk prediction based on findings from genome-wide
association studies that we will perform in the sub-cohort who developed CA-CRC. An impact of this work will
be identification of genetic predictors of CA-CRC in Veterans using data from advanced multi-omic platforms.
 The long-term goal of this research is to shift the paradigm of cancer surveillance used both in the VA
and more broadly to move beyond fixed intervals that mainly rely on presence/absence of dysplasia toward a
conceptual model that incorporates cancer evolution mechanisms and genomics. Our main objective for this
project is to apply these techniques for Veterans with IBD colitis, and herein we will design a novel framework,
MOSAIC, for the Mathematical Optimization of Surveillance Ages to Intercept colitis-associated
Colorectal cancer. To modernize outdated guidelines, we will first understand how CA-CRC arises in patients
with IBD colitis using multiscale data, and then apply and validate this knowledge in a large VA cohort. The three
specific aims for our project are: 1) Quantify IBD colitis incidence rates in MVP and derive polygenic risk scores;
2) Create mathematical models for IBD carcinogenesis that include biophysical details for evolution; and 3)
Optimize patient surveillance strategies to effecti...

## Key facts

- **NIH application ID:** 10581069
- **Project number:** 1I01BX005958-01A1
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Kathleen M. Curtius
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10581069

## Citation

> US National Institutes of Health, RePORTER application 10581069, Mathematical Optimization of Surveillance Ages to Intercept colitis-associated Colorectal cancer (MOSAIC) (1I01BX005958-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10581069. Licensed CC0.

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