Targeting Diet-Driven Inflammation for Colorectal Cancer Prevention in High-Risk Adults: A Biomarker-Guided Approach

SUMMARY Colorectal cancer (CRC) is the second leading cause of cancer death in the United States, with incidence rising alarmingly among younger adults and non-white populations. Chronic inflammation, driven in part by poor diet quality, is a key modifiable risk factor for CRC. However, current clinical tools lack the precision to identify individuals at elevated CRC risk due to pro-inflammatory diets. There is an urgent need for objective, scalable biomarkers that can quantify dietary inflammation and guide personalized prevention strategies. We developed the reversed Empirical Dietary Inflammatory Pattern (rEDIP) biomarker score—a novel, poly- metabolite blood-based biomarker that quantifies the inflammatory potential of diet. Derived from nutritional metabolomics and validated in over 20,000 adults across 12 global cohorts, the rEDIP score reflects habitual dietary intake and predicts CRC risk independent of traditional risk factors. This biomarker captures the synergistic effects of food combinations on systemic inflammation, offering a more precise and culturally adaptable measure than conventional dietary indices. This R01 application proposes to translate the rEDIP biomarker score into clinical practice through three specific aims. Our central hypothesis is that the rEDIP biomarker score is a robust indicator of dietary inflammation that is responsive to diet intervention. Aim 1 will evaluate the association between the rEDIP score and systemic and colon tissue-specific inflammation in 200 adults undergoing colonoscopy, and test for differences by colorectal adenoma severity. Aim 2 will test the efficacy of a 12-week randomized controlled trial of a precision nutrition intervention guided by the rEDIP score in 126 adults with high-risk adenomas, assessing changes in the biomarker and systemic inflammation. Aim 3 will externally validate the rEDIP score using already generated metabolomic data from a tightly controlled 14-day feeding study of habitual diet in 153 adults. This study will establish the rEDIP biomarker score as a clinically actionable tool for identifying individuals at elevated CRC risk due to diet-related inflammation. By integrating this biomarker into gastroenterology workflows and delivering personalized dietary interventions, we aim to intercept inflammation early, reduce CRC incidence, and advance precision nutrition in cancer prevention. Project Number: 1R01CA313949-01 | Fiscal Year: 2026 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: Mary Playdon (+1 co-PI) | Institution: UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH, SALT LAKE CITY, UT | Award Amount: $654,226 | Activity Code: R01 | Study Section: Cancer Prevention Study Section[CPSS] View on NIH RePORTER: https://reporter.nih.gov/project-details/11368842