Faculty, Staff and Student Publications

Language

English

Publication Date

2-1-2026

Journal

International Journal of Cancer

DOI

10.1002/ijc.70090

PMID

40857027

PMCID

PMC12670333

PubMedCentral® Posted Date

8-26-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Human fatty acid binding protein‐4 (FABP‐4), a protein elevated in obesity that promotes colon cancer cell invasiveness and metastasis, may be associated with higher mortality in individuals with colorectal cancer (CRC) and may serve as a mediator of the obesity–mortality association in these individuals. We used a causal diagram to inform covariate selection and applied Cox proportional hazards models to estimate hazard ratios (HRs) for CRC‐specific, non‐CRC‐specific, and all‐cause mortality by FABP‐4 levels measured in baseline blood samples from 1371 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. Competing risk analyses were adapted for CRC and non‐CRC deaths. Mediation analyses were conducted to estimate total effects (TEs), direct effects (DEs), and mediation proportions (MPs) by FABP‐4 of pre‐diagnostic body mass index (BMI) on mortality. In the fully adjusted model including BMI, higher circulating FABP‐4 concentrations were associated with higher CRC mortality (HRQ4vsQ1 = 1.49; 95% CI: 1.11–2.00) and all‐cause mortality (HRQ4vsQ1 = 1.49; 95% CI: 1.15–1.93), but not statistically associated with non‐CRC mortality (HRQ4vsQ1 = 1.51; 95% CI: 0.82–2.76). The TE and DE per 5 kg/m2 of BMI on all‐cause mortality were 1.21; 95% CI: 1.10–1.34, and 1.13; 95% CI: 1.02–1.26, respectively, with a MP of 34.5% (p = .002) by FABP‐4. For CRC‐specific and non‐CRC‐specific mortality, MPs by FABP‐4 were 33.7% (p = .03) and 36.1% (p = .02), respectively. In conclusion, higher concentrations of FABP‐4 were associated with higher CRC‐specific and all‐cause mortality in individuals with CRC. FABP‐4 was a significant partial mediator of the adiposity‐mortality relationship in individuals with CRC.

Keywords

Humans, Fatty Acid-Binding Proteins, Colorectal Neoplasms, Male, Female, Middle Aged, Prospective Studies, Europe, Aged, Body Mass Index, Biomarkers, Tumor, Proportional Hazards Models, Obesity, Risk Factors, EPIC, FABP‐4, human fatty acid binding protein‐4, incident colorectal cancer, mortality

Published Open-Access

yes

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