Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany; Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Biobank Technology Platform, Berlin, Germany.
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Inflammation Biology, School of Immunology and Microbial Sciences, King’s College London, London, United Kingdom.
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, University of Århus, Århus, Denmark.
Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nutehtal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.
Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia.
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Instituto de Salud Pública de Navarra, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain; Epidemiology of Chronic and Communicable Diseases Group, Biodonostia Health Research Institute, San Sebastián, Spain.
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain.
Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute, CA, Los Angeles, United States.
Division of Gastroenterology and Hepatology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, AZ, Phoenix, United States.
Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States.
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain; Department 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.
Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Research Centre for Hauora and Health, Massey University, Wellington, New Zealand.
Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, PA, Pittsburgh, United States.
Department of Population Science, American Cancer Society, GA, Atlanta, United States.
International Agency for Research on Cancer, World Health Organization, Lyon, France.
Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany; Charité - Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, Berlin, Germany; Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Biobank Technology Platform, Berlin, Germany.
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.
BioMed Central (BMC), 2023. Vol. 21, no 1, article id 391