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

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...

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Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/208644
Acceso en línea:https://hdl.handle.net/2445/208644
Access Level:acceso abierto
Palabra clave:Càncer colorectal
Àcids grassos
Genètica
Colorectal cancer
Fatty acids
Genetics
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spelling Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancerWeiderpass, ElisabeteNimptsch, KatharinaAleksandrova, KrasimiraPham, Thu ThiPapadimitriou, NikosJanke, JürgenChristakoudi, SofiaHeath, Alicia K.Olsen, AnjaTjønneland, AnneSchulze, Matthias B.Katzke, VerenaKaaks, RudolfVan Guelpen, BethanyHarbs, JustinPalli, DomenicoMacciotta, AlessandraPasanisi, FabrizioColorado-Yohar, SandraGuevara, MarcelaAmiano, PilarGrioni, SaraJakszyn, PaulaFigueiredo, Jane C.Samadder, N. JewelLi, Christopher I.Moreno Aguado, VíctorPotter, John D.Schoen, Robert E.Um, Caroline Y.Jenab, MazdaGunter, Marc J.Pischon, TobiasCàncer colorectalÀcids grassosGenèticaColorectal cancerFatty acidsGeneticsBackground: 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 Central2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/208644Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s12916-023-03104-1BMC Medicine, 2023, vol. 21, num.1https://doi.org/10.1186/s12916-023-03104-1cc-by (c) Nimptsch, K. et al., 2023http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2086442026-05-27T06:46:51Z
dc.title.none.fl_str_mv Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer
title Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer
spellingShingle Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer
Weiderpass, Elisabete
Càncer colorectal
Àcids grassos
Genètica
Colorectal cancer
Fatty acids
Genetics
title_short Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer
title_full Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer
title_fullStr Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer
title_full_unstemmed Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer
title_sort Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer
dc.creator.none.fl_str_mv 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
author Weiderpass, Elisabete
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer colorectal
Àcids grassos
Genètica
Colorectal cancer
Fatty acids
Genetics
topic Càncer colorectal
Àcids grassos
Genètica
Colorectal cancer
Fatty acids
Genetics
description 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.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/208644
url https://hdl.handle.net/2445/208644
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s12916-023-03104-1
BMC Medicine, 2023, vol. 21, num.1
https://doi.org/10.1186/s12916-023-03104-1
dc.rights.none.fl_str_mv cc-by (c) Nimptsch, K. et al., 2023
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Nimptsch, K. et al., 2023
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Clíniques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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