Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer BMC Medicine
Abstract Methods Results Consent for publication Competing interests Footnotes References Associated Data Supplementary Materials Data Availability Statement 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. Supplementary Information The online version contains supplementary material available at 10.1186/s12916-023-03104-1. Keywords: FABP-4, Colorectal cancer, Mendelian randomization
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Katharina Nimptsch, Krasimira Aleksandrova, Thu Thi Pham et al.. 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). https://doi.org/10.1186/s12916-023-03104-1 Katharina Nimptsch, Krasimira Aleksandrova, Thu Thi Pham, Nikos Papadimitriou, Jürgen Janke, Sofia Christakoudi, Alicia Heath, Anja Olsen, Anne Tjønneland, Matthias B Schulze, Verena Katzke, Rudolf Kaaks, Bethany van Guelpen, Justin Harbs, Domenico Palli, Alessandra Macciotta, Fabrizio Pasanisi, Sandra Milena Colorado Yohar, Marcela Guevara, Pilar Amiano, Sara Grioni, Paula Gabriela Jakszyn, Jane C Figueiredo, N Jewel Samadder, Christopher I Li, Victor Moreno, John D Potter, Robert E Schoen, Caroline Y Um, Elisabete Weiderpass, Mazda Jenab, Marc J Gunter, Tobias Pischon
1Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany 2Department Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany 3Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany 4Charité - Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, Berlin, Germany 5Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France 6Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Biobank Technology Platform, Berlin, Germany 7Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK 8Department of Inflammation Biology, School of Immunology and Microbial Sciences, King’s College London, London, UK 9Danish Cancer Society Research Center, Copenhagen, Denmark 10Department of Public Health, University of Århus, Århus, Denmark 11Department of Public Health, University of Copenhagen, Copenhagen, Denmark 12Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nutehtal, Germany 13Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany 14Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany 15Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden 16Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden 17Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy 18Department of Clinical and Biological Sciences, University of Turin, Turin, Italy 19Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy 20Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain 21CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain 22Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia 23Instituto de Salud Pública de Navarra, Pamplona, 31003 Spain 24Navarra Institute for Health Research (IdiSNA), Pamplona, 31008 Spain 25Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain 26Epidemiology of Chronic and Communicable Diseases Group, Biodonostia Health Research Institute, San Sebastián, Spain 27Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, 20133 Italy 28Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain 29Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain 30Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA USA 31Division of Gastroenterology and Hepatology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Phoenix, AZ USA 32Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA USA 33Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain 34Department of Clinical Sciences, Faculty of Medicine and Health Sciences and Universitat de Barcelona Institute of Complex Systems (UBICS), University of Barcelona (UB), L’Hospitalet de Llobregat, Barcelona, Spain 35Research Centre for Hauora and Health, Massey University, Wellington, New Zealand 36Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA USA 37Department of Population Science, American Cancer Society, Atlanta, GA USA 38International Agency for Research on Cancer, World Health Organization, Lyon, France 