1. Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause
- Author
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Adonina Tardón, Marina Riera-Ponsati, Pablo Fernández Navarro, Eva Ardanaz, Mariona Bustamante, Beatriz Pérez-Gómez, Anna Díez-Villanueva, Gemma Ibáñez-Sanz, Inmaculada Salcedo Bellido, Gemma Castaño-Vinyals, Victor Moreno, José Juan Jiménez Moleón, Luis Ortega-Valín, Nieves Ascunce, Jone M. Altzibar, Tania Fernández-Villa, Dolores Salas, Javier Llorca, Marina Pollán, Nuria Aragonés, Valle Olmos Juste, Guillermo Fernández-Tardón, Camilo Palazuelos, Marta Crous-Bou, Pilar Amiano, Rocío Capelo Álvarez, Manolis Kogevinas, Universidad de Cantabria, Instituto de Salud Carlos III, Fundación Marqués de Valdecilla, Junta de Castilla y León (España), Regional Government of Andalusia (España), Generalitat Valenciana (España), Fundación La Caixa, Basque Government (España), Gobierno de la Región de Murcia (España), Unión Europea. Comisión Europea, Fundación Vencer el Cáncer, Government of Catalonia (España), Fundación Caja de Ahorros de Asturias, University of Oviedo (España), and Sociedad Catalana de Digestología
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Male ,0301 basic medicine ,Trastorns del metabolisme ,lcsh:Medicine ,Endocrine diseases ,Disylipidaemia ,Cancer prevention ,0302 clinical medicine ,Risk Factors ,Cost action ,European commission ,lcsh:Science ,Aged, 80 and over ,Multidisciplinary ,Incidence ,Middle Aged ,Prognosis ,Lipids ,Disorders of metabolism ,Còlon -- Càncer ,030220 oncology & carcinogenesis ,language ,Female ,Christian ministry ,lipids (amino acids, peptides, and proteins) ,Colorectal Neoplasms ,Adult ,Lípids--Metabolisme--Trastorns ,Polymorphism, Single Nucleotide ,Article ,Young Adult ,03 medical and health sciences ,Cancer epidemiology ,Càncer colorectal ,Political science ,Mendelian randomization ,Humans ,Genetic Predisposition to Disease ,Malalties de les glàndules endocrines ,Aged ,Dyslipidemias ,lcsh:R ,Mendelian Randomization Analysis ,Colorectal cancer ,language.human_language ,030104 developmental biology ,Spain ,Case-Control Studies ,lcsh:Q ,Catalan ,Humanities ,Follow-Up Studies ,Genome-Wide Association Study - Abstract
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 casecontrol 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., This work was supported by the ‘Acción Transversal del Cancer’, approved by the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III, co-founded by FEDER funds –‘a way to build Europe’ [grants PI08/1770, PI08/0533, PI08/1359, PI09/00773, PI09/01286, PI09/01903, PI09/02078, PI09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/00613, PI17/00092 and PI15/00069]. Support was also provided by the Fundación Marqués de Valdecilla (grant API 10/09]; the Junta de Castilla y León [grant LE22A10-2]; the Consejería de Salud of the Junta de Andalucía [2009-S0143]; the Conselleria de Sanitat of the Generalitat Valenciana [grant AP 061/10]; the Recercaixa [grant 2010ACUP 00310]; the Regional Government of the Basque Country; the Consejería de Sanidad de la Región de Murcia; European Commission grants FOOD-CT-2006-036224-HIWATE; the Spanish Association Against Cancer (AECC) Scientific Foundation; the Catalan Government DURSI [grants 2017SGR723 and 2014SGR850]; the Fundación Caja de Ahorros de Asturias; the University of Oviedo; Societat Catalana de Digestologia; and COST action CA17118 Transcoloncan.
- Published
- 2019
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