Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/22/2025
Publication Date: 10/28/2025
Citation: Shi, N., Hoobler, R., Harewood, R., Toland, A.E., Albanes, D., Bouras, E., Gunter, M.J., Liao, L.M., Moore, S.C., Ricceri, F., Rotter, J.I., Sinha, R., Stolzenberg-Solomon, R., Tjonneland, A., Wood, A.C., Yu, D., Playdon, M.C., Tabung, F.K. 2025. Insulinemic and inflammatory dietary patterns in relation to colorectal cancer risk: A dietary data harmonization study of one million participants across six cohorts in the COMETS Consortium. The American Journal of Clinical Nutrition. https://doi.org/10.1016/j.ajcnut.2025.10.016.
DOI: https://doi.org/10.1016/j.ajcnut.2025.10.016

Interpretive Summary: Colorectal cancer is one of the most common cancers worldwide and is strongly influenced by diet, but scientists have struggled to pinpoint which types of eating patterns raise or lower risk. This study combined data from over one million adults across six major population studies in the U.S. and Europe to examine whether diets that lower inflammation or insulin levels are linked to reduced colorectal cancer risk. Researchers in Houston collaborated with teams across the US to create harmonized measures of diet quality, and used these to compare three dietary patterns, including the Healthy Eating Index (HEI) score – a measure of adherence to the USDA's Dietary Guidelines for Americans - as well as two data-driven scores that reflect the diet's potential to cause inflammation or raise insulin levels. People who ate diets with lower inflammatory and insulinemic potential had up to a 23% lower risk of developing colorectal cancer compared to those with higher-risk diets. These findings suggest that eating patterns that keep blood sugar and inflammation low may help prevent colorectal cancer. The results are important for clinicians and policymakers designing dietary guidelines and for the public seeking evidence-based ways to reduce cancer risk.

Technical Abstract: Inflammatory and insulinemic dietary patterns have been associated with colorectal cancer (CRC) risk, but generalizability across diverse populations with heterogeneous food supplies and dietary behaviors has not been established. We harmonized disparate dietary and covariate data on a large scale to compute the reverse Empirical Dietary Index for Hyperinsulinemia-rEDIH, reverse Empirical Dietary Inflammatory Pattern-rEDIP, and Healthy Eating Index (HEI)-2015 scores, and tested their associations with CRC risk. We leveraged data among 501,892 women and 407,390 men from six cohorts across the U.S. (NIH-AARP, MESA, PLCO, SCCS) and Europe (EPIC, ATBC) with varying sociodemographic characteristics, participating in the Consortium of Metabolomics Studies. We harmonized nomenclature and nutritional information for more than 800 unique food items across cohorts. We used multivariable-adjusted Cox regression, adjusting for demographic, clinical, and lifestyle factors, to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between the dietary indices and CRC risk per cohort, then meta-analyzed the estimates. During a median follow-up of 14.9 years, 16,525 incident CRC cases were diagnosed. Participants in the highest quintile of rEDIH (low-insulinemic diet) had an 18% reduced risk of CRC (HR 0.82; 95% CI: 0.78, 0.86) compared to those in the lowest quintile. For the same comparison, similar risk reductions were observed for rEDIP (anti-inflammatory diet) (HR 0.84; 95% CI: 0.80, 0.89) and HEI-2015 (overall dietary quality) (HR 0.80; 95% CI: 0.76, 0.85). Heterogeneity between cohorts in the meta-analyzed estimates was low for rEDIH (I**2=22.3%) compared to rEDIP (I**2=62.5%) and HEI-2015 (I**2=83.9%). Using carefully harmonized data from nearly one million individuals in the U.S. and Europe, we observed significant CRC risk reduction with habitual intake of low-insulinemic and anti-inflammatory dietary patterns, comparable to higher overall dietary quality. Study findings underscore the utility of these dietary patterns for global cancer prevention efforts.