Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause

Ibáñez Sanz, Gemma; Díez Villanueva, Anna; Riera Ponsati, Marina; Fernández Villa, Tania; Fernández Navarro, Pablo; Bustamante Pineda, Mariona; Llorca, Javier; Amiano, Pilar; Ascunce, Nieves; Fernández Tardón, Guillermo; Salcedo Bellido, Inmaculada; Salas, Dolores; Capelo Álvarez, Rocío; Crous Bou, Marta; Ortega Valín, Luis; Pérez Gómez, Beatriz; Castaño-Vinyals, Gemma; Palazuelos-Calderón, Camilo; Altzibar, Jone M.; Ardanaz, Eva; Tardón, Adonina; Jiménez Moleón, José Juan; Olmos Juste, Valle; Aragonès Sanz, Núria; Pollán, Marina; Kogevinas, Manolis; Moreno Aguado, Víctor

Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause

Dyslipidemia and statin use have been associated with colorectal cancer (CRC), but prospective studies have shown mixed results. We aimed to determine whether dyslipidemia is causally linked to CRC risk using a Mendelian randomization approach and to explore the association of statins with CRC. A ca...

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Autores:	Ibáñez Sanz, Gemma, Díez Villanueva, Anna, Riera Ponsati, Marina, Fernández Villa, Tania, Fernández Navarro, Pablo, Bustamante Pineda, Mariona, Llorca, Javier, Amiano, Pilar, Ascunce, Nieves, Fernández Tardón, Guillermo, Salcedo Bellido, Inmaculada, Salas, Dolores, Capelo Álvarez, Rocío, Crous Bou, Marta, Ortega Valín, Luis, Pérez Gómez, Beatriz, Castaño-Vinyals, Gemma, Palazuelos-Calderón, Camilo, Altzibar, Jone M., Ardanaz, Eva, Tardón, Adonina, Jiménez Moleón, José Juan, Olmos Juste, Valle, Aragonès Sanz, Núria, Pollán, Marina, Kogevinas, Manolis, Moreno Aguado, Víctor
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2019
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/171331
Acceso en línea:	https://hdl.handle.net/2445/171331
Access Level:	acceso abierto
Palabra clave:	Càncer colorectal Malalties de les glàndules endocrines Trastorns del metabolisme Colorectal cancer Endocrine diseases Disorders of metabolism

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spelling	Mendelian randomization analysis rules out disylipidaemia as colorectal cancer causeIbáñez Sanz, GemmaDíez Villanueva, AnnaRiera Ponsati, MarinaFernández Villa, TaniaFernández Navarro, PabloBustamante Pineda, MarionaLlorca, JavierAmiano, PilarAscunce, NievesFernández Tardón, GuillermoSalcedo Bellido, InmaculadaSalas, DoloresCapelo Álvarez, RocíoCrous Bou, MartaOrtega Valín, LuisPérez Gómez, BeatrizCastaño-Vinyals, GemmaPalazuelos-Calderón, CamiloAltzibar, Jone M.Ardanaz, EvaTardón, AdoninaJiménez Moleón, José JuanOlmos Juste, ValleAragonès Sanz, NúriaPollán, MarinaKogevinas, ManolisMoreno Aguado, VíctorCàncer colorectalMalalties de les glàndules endocrinesTrastorns del metabolismeColorectal cancerEndocrine diseasesDisorders of metabolismDyslipidemia and statin use have been associated with colorectal cancer (CRC), but prospective studies have shown mixed results. We aimed to determine whether dyslipidemia is causally linked to CRC risk using a Mendelian randomization approach and to explore the association of statins with CRC. A case-control study was performed including 1336 CRC cases and 2744 controls (MCC-Spain). Subjects were administered an epidemiological questionnaire and were genotyped with an array which included polymorphisms associated with blood lipids levels, selected to avoid pleiotropy. Four genetic lipid scores specific for triglycerides (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), or total cholesterol (TC) were created as the count of risk alleles. The genetic lipid scores were not associated with CRC. The ORs per 10 risk alleles, were for TG 0.91 (95%CI: 0.72-1.16, p = 0.44), for HDL 1.14 (95%CI: 0.95-1.37, p = 0.16), for LDL 0.97 (95%CI: 0.81-1.16, p = 0.73), and for TC 0.98 (95%CI: 0.84-1.17, p = 0.88). The LDL and TC genetic risk scores were associated with statin use, but not the HDL or TG. Statin use, overall, was a non-significant protective factor for CRC (OR 0.84; 95%CI: 0.70-1.01, p = 0.060), but lipophilic statins were associated with a CRC risk reduction (OR 0.78; 95%CI 0.66-0.96, p = 0.018). Using the Mendelian randomization approach, our study does not support the hypothesis that lipid levels are associated with the risk of CRC. This study does not rule out, however, a possible protective effect of statins in CRC by a mechanism unrelated to lipid levels.Nature Publishing Group2020202020192020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion9 p.application/pdfhttps://hdl.handle.net/2445/171331Articles publicats en revistes (Ciències Clíniques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/s41598-019-49880-wScientific Reports, 2019, vol. 9, p. 13407https://doi.org/10.1038/s41598-019-49880-wcc-by (c) Ibáñez Sanz, Gemma et al., 2019http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1713312026-05-29T05:05:01Z
dc.title.none.fl_str_mv	Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause
title	Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause
spellingShingle	Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause Ibáñez Sanz, Gemma Càncer colorectal Malalties de les glàndules endocrines Trastorns del metabolisme Colorectal cancer Endocrine diseases Disorders of metabolism
title_short	Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause
title_full	Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause
title_fullStr	Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause
title_full_unstemmed	Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause
title_sort	Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause
dc.creator.none.fl_str_mv	Ibáñez Sanz, Gemma Díez Villanueva, Anna Riera Ponsati, Marina Fernández Villa, Tania Fernández Navarro, Pablo Bustamante Pineda, Mariona Llorca, Javier Amiano, Pilar Ascunce, Nieves Fernández Tardón, Guillermo Salcedo Bellido, Inmaculada Salas, Dolores Capelo Álvarez, Rocío Crous Bou, Marta Ortega Valín, Luis Pérez Gómez, Beatriz Castaño-Vinyals, Gemma Palazuelos-Calderón, Camilo Altzibar, Jone M. Ardanaz, Eva Tardón, Adonina Jiménez Moleón, José Juan Olmos Juste, Valle Aragonès Sanz, Núria Pollán, Marina Kogevinas, Manolis Moreno Aguado, Víctor
author	Ibáñez Sanz, Gemma
author_facet	Ibáñez Sanz, Gemma Díez Villanueva, Anna Riera Ponsati, Marina Fernández Villa, Tania Fernández Navarro, Pablo Bustamante Pineda, Mariona Llorca, Javier Amiano, Pilar Ascunce, Nieves Fernández Tardón, Guillermo Salcedo Bellido, Inmaculada Salas, Dolores Capelo Álvarez, Rocío Crous Bou, Marta Ortega Valín, Luis Pérez Gómez, Beatriz Castaño-Vinyals, Gemma Palazuelos-Calderón, Camilo Altzibar, Jone M. Ardanaz, Eva Tardón, Adonina Jiménez Moleón, José Juan Olmos Juste, Valle Aragonès Sanz, Núria Pollán, Marina Kogevinas, Manolis Moreno Aguado, Víctor
author_role	author
author2	Díez Villanueva, Anna Riera Ponsati, Marina Fernández Villa, Tania Fernández Navarro, Pablo Bustamante Pineda, Mariona Llorca, Javier Amiano, Pilar Ascunce, Nieves Fernández Tardón, Guillermo Salcedo Bellido, Inmaculada Salas, Dolores Capelo Álvarez, Rocío Crous Bou, Marta Ortega Valín, Luis Pérez Gómez, Beatriz Castaño-Vinyals, Gemma Palazuelos-Calderón, Camilo Altzibar, Jone M. Ardanaz, Eva Tardón, Adonina Jiménez Moleón, José Juan Olmos Juste, Valle Aragonès Sanz, Núria Pollán, Marina Kogevinas, Manolis Moreno Aguado, Víctor
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
dc.subject.none.fl_str_mv	Càncer colorectal Malalties de les glàndules endocrines Trastorns del metabolisme Colorectal cancer Endocrine diseases Disorders of metabolism
topic	Càncer colorectal Malalties de les glàndules endocrines Trastorns del metabolisme Colorectal cancer Endocrine diseases Disorders of metabolism
description	Dyslipidemia and statin use have been associated with colorectal cancer (CRC), but prospective studies have shown mixed results. We aimed to determine whether dyslipidemia is causally linked to CRC risk using a Mendelian randomization approach and to explore the association of statins with CRC. A case-control study was performed including 1336 CRC cases and 2744 controls (MCC-Spain). Subjects were administered an epidemiological questionnaire and were genotyped with an array which included polymorphisms associated with blood lipids levels, selected to avoid pleiotropy. Four genetic lipid scores specific for triglycerides (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), or total cholesterol (TC) were created as the count of risk alleles. The genetic lipid scores were not associated with CRC. The ORs per 10 risk alleles, were for TG 0.91 (95%CI: 0.72-1.16, p = 0.44), for HDL 1.14 (95%CI: 0.95-1.37, p = 0.16), for LDL 0.97 (95%CI: 0.81-1.16, p = 0.73), and for TC 0.98 (95%CI: 0.84-1.17, p = 0.88). The LDL and TC genetic risk scores were associated with statin use, but not the HDL or TG. Statin use, overall, was a non-significant protective factor for CRC (OR 0.84; 95%CI: 0.70-1.01, p = 0.060), but lipophilic statins were associated with a CRC risk reduction (OR 0.78; 95%CI 0.66-0.96, p = 0.018). Using the Mendelian randomization approach, our study does not support the hypothesis that lipid levels are associated with the risk of CRC. This study does not rule out, however, a possible protective effect of statins in CRC by a mechanism unrelated to lipid levels.
publishDate	2019
dc.date.none.fl_str_mv	2019 2020 2020 2020
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/2445/171331
url	https://hdl.handle.net/2445/171331
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/10.1038/s41598-019-49880-w Scientific Reports, 2019, vol. 9, p. 13407 https://doi.org/10.1038/s41598-019-49880-w
dc.rights.none.fl_str_mv	cc-by (c) Ibáñez Sanz, Gemma et al., 2019 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by (c) Ibáñez Sanz, Gemma et al., 2019 http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	9 p. application/pdf
dc.publisher.none.fl_str_mv	Nature Publishing Group
publisher.none.fl_str_mv	Nature Publishing Group
dc.source.none.fl_str_mv	Articles publicats en revistes (Ciències Clíniques) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause

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