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| Item Type: | Article |
|---|---|
| Title: | 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 |
| Creators Name: | Pham, Thu Thi, Nimptsch, Katharina, Aleksandrova, Krasimira, Jenab, Mazda, Fedirko, Veronika, Olsen, Anja, Tjønneland, Anne, Cadeau, Claire, Severi, Gianluca, Schulze, Matthias B., Fortner, Renée Turzanski, Katzke, Verena, Agnoli, Claudia, Sacerdote, Carlotta, Tumino, Rosario, Signoriello, Simona, Trobajo-Sanmartín, Camino, Gómez, Jesús-Humberto, Chirlaque, Maria-Dolores, Sánchez, Maria Jose, Crous-Bou, Marta, May, Anne, Heath, Alicia K., Aune, Dagfinn, Weiderpass, Elisabete and Pischon, Tobias |
| 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(Q4vsQ1) = 1.49; 95% CI: 1.11–2.00) and all-cause mortality (HR(Q4vsQ1) = 1.49; 95% CI: 1.15–1.93), but not statistically associated with non-CRC mortality (HR(Q4vsQ1) = 1.51; 95% CI: 0.82–2.76). The TE and DE per 5 kg/m(2) 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: | EPIC, FABP-4, Human Fatty Acid Binding Protein-4, Incident Colorectal Cancer, Mortality |
| Source: | International Journal of Cancer |
| ISSN: | 0020-7136 |
| Publisher: | Wiley |
| Date: | 26 August 2025 |
| Official Publication: | https://doi.org/10.1002/ijc.70090 |
| PubMed: | View item in PubMed |
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