Circulating fatty acid binding protein 4 ( <scp>FABP</scp> ‐4) concentrations and mortality in individuals with colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study

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 (HR<sub>Q4vsQ1</sub> = 1.49; 95% CI: 1.11-2.00) and all-cause mortality (HR<sub>Q4vsQ1</sub> = 1.49; 95% CI: 1.15-1.93), but not statistically associated with non-CRC mortality (HR<sub>Q4vsQ1</sub> = 1.51; 95% CI: 0.82-2.76). The TE and DE per 5 kg/m<sup>2</sup> 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.

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Journal
International Journal of Cancer
Published
2025-08-26
DOI
https://doi.org/10.1002/ijc.70090
Primary Topic
Peroxisome Proliferator-Activated Receptors
Type
article
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0.00

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article

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

Simona Signoriello, Alicia K. Heath, Krasimira Aleksandrova, Claire Cadeau et al.
International Journal of Cancer
Peroxisome Proliferator-Activated Receptors
article

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

Simona Signoriello, Alicia K. Heath, Krasimira Aleksandrova, Claire Cadeau, María‐Dolores Chirlaque, Claudia Agnoli, Veronika Fedirko, Carlotta Sacerdote, Matthias Bernd Schulze, Anne M. May, ­Rosario ­Tumino, Mazda Jenab, Renée T. Fortner, Tobias Pischon, Jesús‐Humberto Gómez, Dagfinn Aune, Verena Katzke, Camino Trobajo‐Sanmartín, Marta Crous‐Bou, Elisabete Weiderpass, Anne Marie Tjønneland, Katharina Nimptsch, Gianluca Severi, Thu Thi Pham, María‐José Sánchez, Anja Olsen
article en

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 (HR<sub>Q4vsQ1</sub> = 1.49; 95% CI: 1.11-2.00) and all-cause mortality (HR<sub>Q4vsQ1</sub> = 1.49; 95% CI: 1.15-1.93), but not statistically associated with non-CRC mortality (HR<sub>Q4vsQ1</sub> = 1.51; 95% CI: 0.82-2.76). The TE and DE per 5 kg/m<sup>2</sup> 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.

International Journal of CancerVol. 158(3)
Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), University of Copenhagen (DK), Norwegian Institute of Public Health (NO), The University of Texas MD Anderson Cancer Center (US), Harvard University (US), Emory University (US), Inserm (FR), University of Potsdam (DE), German Cancer Research Center (DE), University of Bremen (DE), OsloMet – Oslo Metropolitan University (NO), Université de Versailles Saint-Quentin-en-Yvelines (FR), Max Delbrück Center (DE), Heidelberg University (DE), Université Paris-Saclay (FR), Aarhus University Hospital (DK), University Medical Center Utrecht (NL), Humboldt-Universität zu Berlin (DE), Instituto de Salud Pública de Navarra (ES), Institut d'Investigació Biomédica de Bellvitge (ES), Institute of Cancer Research (CA), Centre de recherche en Epidémiologie et Santé des Populations (FR), Navarre Institute of Health Research (ES), Instituto de Investigación Biosanitaria de Granada (ES), Leibniz Institute for Prevention Research and Epidemiology - BIPS (DE), University of Campania "Luigi Vanvitelli" (IT), Italian Association for Cancer Research (IT), Cancer Registry of Norway (NO), Instituto Murciano de Investigación Biosanitaria (ES), Danish Cancer Society (DK), Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), Novamont (Italy) (IT), German Institute of Human Nutrition (DE), Centre international de recherche sur le cancer (FR), University of Florence (IT), Imperial College London (GB), Andalusian School of Public Health (ES), Freie Universität Berlin (DE), Charité - Universitätsmedizin Berlin (DE)
World Health Organization, Cancer Prevention and Research Institute of Texas, Kræftens Bekæmpelse, Deutsches Krebsforschungszentrum, Cancer Research UK, National Institute for Health and Care Research, Imperial College London, Institut National de la Santé et de la Recherche Médicale, Bundesministerium für Bildung und Forschung, Cancerfonden, Ligue Contre le Cancer, Vetenskapsrådet, Associazione Italiana per la Ricerca sul Cancro, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, Medical Research Council, World Cancer Research Fund, Instituto de Salud Carlos III, Rijksinstituut voor Volksgezondheid en Milieu, NIHR Imperial Biomedical Research Centre, School of Public Health, Imperial College London
Openalex Percentile: Top 80%
Peroxisome Proliferator-Activated Receptors
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