2026-04-14T04:11:19Zhttps://recercat.cat/oai/requestoai:recercat.cat:2445/2086442025-12-05T13:15:18Zcom_2072_1057col_2072_478798col_2072_478916col_2072_478917
Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer
Weiderpass, Elisabete
Nimptsch, Katharina
Aleksandrova, Krasimira
Pham, Thu Thi
Papadimitriou, Nikos
Janke, Jürgen
Christakoudi, Sofia
Heath, Alicia K.
Olsen, Anja
Tjønneland, Anne
Schulze, Matthias B.
Katzke, Verena
Kaaks, Rudolf
Van Guelpen, Bethany
Harbs, Justin
Palli, Domenico
Macciotta, Alessandra
Pasanisi, Fabrizio
Colorado-Yohar, Sandra
Guevara, Marcela
Amiano, Pilar
Grioni, Sara
Jakszyn, Paula
Figueiredo, Jane C.
Samadder, N. Jewel
Li, Christopher I.
Moreno Aguado, Víctor
Potter, John D.
Schoen, Robert E.
Um, Caroline Y.
Jenab, Mazda
Gunter, Marc J.
Pischon, Tobias
Càncer colorectal
Àcids grassos
Genètica
Colorectal cancer
Fatty acids
Genetics
Background: Fatty acid binding protein 4 (FABP-4) is a lipid-binding adipokine upregulated in obesity, which may facilitate fatty acid supply for tumor growth and promote insulin resistance and inflammation and may thus play a role in colorectal cancer (CRC) development. We aimed to investigate the association between circulating FABP-4 and CRC and to assess potential causality using a Mendelian randomization (MR) approach. Methods: The association between pre-diagnostic plasma measurements of FABP-4 and CRC risk was investigated in a nested case-control study in 1324 CRC cases and the same number of matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A two-sample Mendelian randomization study was conducted based on three genetic variants (1 cis, 2 trans) associated with circulating FABP-4 identified in a published genome-wide association study (discovery n = 20,436) and data from 58,131 CRC cases and 67,347 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Results: In conditional logistic regression models adjusted for potential confounders including body size, the estimated relative risk, RR (95% confidence interval, CI) per one standard deviation, SD (8.9 ng/mL) higher FABP-4 concentration was 1.01 (0.92, 1.12) overall, 0.95 (0.80, 1.13) in men and 1.09 (0.95, 1.25) in women. Genetically determined higher FABP-4 was not associated with colorectal cancer risk (RR per FABP-4 SD was 1.10 (0.95, 1.27) overall, 1.03 (0.84, 1.26) in men and 1.21 (0.98, 1.48) in women). However, in a cis-MR approach, a statistically significant association was observed in women (RR 1.56, 1.09, 2.23) but not overall (RR 1.23, 0.97, 1.57) or in men (0.99, 0.71, 1.37). Conclusions: Taken together, these analyses provide no support for a causal role of circulating FABP-4 in the development of CRC, although the cis-MR provides some evidence for a positive association in women, which may deserve to be investigated further.
2024-03-11T18:06:29Z
2024-03-11T18:06:29Z
2023-10-13
2024-03-11T18:06:29Z
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
1741-7015
https://hdl.handle.net/2445/208644
743677
eng
Reproducció del document publicat a: https://doi.org/10.1186/s12916-023-03104-1
BMC Medicine, 2023, vol. 21, num.1
https://doi.org/10.1186/s12916-023-03104-1
cc-by (c) Nimptsch, K. et al., 2023
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
16 p.
application/pdf
BioMed Central
Articles publicats en revistes (Ciències Clíniques)