| 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 |
| Authors: |
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,María-Dolores; Sánchez,Maria-Jose; Crous-Bou,Marta; May, Anne; Heath,Alicia; Aune,Dagfinn; Weiderpass,Elisabete; Pischon,Tobias; Epi Kanker; Cancer; JC onderzoeksprogramma Cancer |
| Publication Year: |
2026 |
| Subject Terms: |
EPIC; FABP-4; human fatty acid binding protein-4; incident colorectal cancer; mortality; Oncology; Cancer Research; Journal Article |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
0020-7136 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/467431 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/467431 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.70FD6AF2 |
| Database: |
BASE |