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Title: | Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer |
Author: | 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 M. 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 |
Keywords: | Càncer colorectal Àcids grassos Genètica Colorectal cancer Fatty acids Genetics |
Issue Date: | 13-Oct-2023 |
Publisher: | BioMed Central |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1186/s12916-023-03104-1 |
It is part of: | BMC Medicine, 2023, vol. 21, num.1 |
URI: | http://hdl.handle.net/2445/208644 |
Related resource: | https://doi.org/10.1186/s12916-023-03104-1 |
ISSN: | 1741-7015 |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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