Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer
-
Published:2023-10-13
Issue:1
Volume:21
Page:
-
ISSN:1741-7015
-
Container-title:BMC Medicine
-
language:en
-
Short-container-title:BMC Med
Author:
Nimptsch Katharina,Aleksandrova Krasimira,Pham Thu Thi,Papadimitriou Nikos,Janke Jürgen,Christakoudi Sofia,Heath Alicia,Olsen Anja,Tjønneland Anne,Schulze Matthias B.,Katzke Verena,Kaaks Rudolf,van Guelpen Bethany,Harbs Justin,Palli Domenico,Macciotta Alessandra,Pasanisi Fabrizio,Yohar Sandra Milena Colorado,Guevara Marcela,Amiano Pilar,Grioni Sara,Jakszyn Paula Gabriela,Figueiredo Jane C.,Samadder N. Jewel,Li Christopher I.,Moreno Victor,Potter John D.,Schoen Robert E.,Um Caroline Y.,Weiderpass Elisabete,Jenab Mazda,Gunter Marc J.,Pischon Tobias
Abstract
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.
Funder
Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft (MDC)
Publisher
Springer Science and Business Media LLC
Reference60 articles.
1. Boord JB, Fazio S, Linton MF. Cytoplasmic fatty acid-binding proteins: emerging roles in metabolism and atherosclerosis. Curr Opin Lipidol. 2002;13(2):141–7. 2. Xu A, Tso AW, Cheung BM, Wang Y, Wat NM, Fong CH, et al. Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study. Circulation. 2007;115(12):1537–43. 3. Xu A, Wang Y, Xu JY, Stejskal D, Tam S, Zhang J, et al. Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clin Chem. 2006;52(3):405–13. 4. Aleksandrova K, Drogan D, Weikert C, Schulze MB, Fritsche A, Boeing H, et al. Fatty acid-binding protein 4 and risk of type 2 diabetes, myocardial infarction, and stroke: a prospective cohort study. J Clin Endocrinol Metab. 2019;104(12):5991–6002. 5. Makowski L, Brittingham KC, Reynolds JM, Suttles J, Hotamisligil GS. The fatty acid-binding protein, aP2, coordinates macrophage cholesterol trafficking and inflammatory activity. Macrophage expression of aP2 impacts peroxisome proliferator-activated receptor gamma and IkappaB kinase activities. J Biol Chem. 2005;280(13):12888–95.
|
|