Journal Article

DKFZ-2025-01786

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Circulating fatty acid binding protein 4 (FABP-4) concentrations and mortality in individuals with colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study.

Pham, T. T. ; Nimptsch, K. ; Aleksandrova, K. ; Jenab, M. ; Fedirko, V. ; Olsen, A. ; Tjønneland, A. ; Cadeau, C. ; Severi, G. ; Schulze, M. B. ; Turzanski-Fortner, R.DKFZ* ; Katzke, V.DKFZ* ; Agnoli, C. ; Sacerdote, C. ; Tumino, R. ; Signoriello, S. ; Trobajo-Sanmartín, C. ; Gómez, J.-H. ; Chirlaque, M.-D. ; Sánchez, M.-J. ; Crous-Bou, M. ; May, A. ; Heath, A. ; Aune, D. ; Weiderpass, E. ; Pischon, T.

2026
Wiley-Liss Bognor Regis

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.

Keyword(s): EPIC ; FABP‐4 ; human fatty acid binding protein‐4 ; incident colorectal cancer ; mortality

Note: 2026 Feb 1;158(3):546-559

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Contributing Institute(s):

1. Krebsepidemiologie (C180)
2. Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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