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2023-10-13

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cc-by (c) Nimptsch, K. et al., 2023
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/208644

Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer

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https://doi.org/10.1186/s12916-023-03104-1

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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.

Matèries

Càncer colorectal, Àcids grassos, Genètica

Matèries (anglès)

Colorectal cancer, Fatty acids, Genetics

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Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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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. Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer. _BMC Medicine_. 2023. Vol. 21, núm. 1. [consulta: 25 de gener de 2026]. ISSN: 1741-7015. [Disponible a: https://hdl.handle.net/2445/208644]

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