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Sci Rep. 2019 Sep 16;9(1):13407. doi: 10.1038/s41598-019-49880-w.

Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause.

Author information

1
Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO) and ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain.
2
Gastroenterology Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Spain.
3
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
4
Grupo de Investigación en Interacciones Gen-Ambiente y Salud. Instituto de Biomedicina (IBIOMED). University of León, León, Spain.
5
Environmental and Cancer Epidemiology Department, National Center of Epidemiology - Instituto de Salud Carlos III, Madrid, Spain.
6
Oncology and Hematology Area, IIS Puerta de Hierro, Cancer Epidemiology Research Group, Madrid, Spain.
7
ISGlobal, Barcelona, Spain.
8
IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
9
University of Pompeu Fabra, Barcelona, Spain.
10
University of Cantabria - IDIVAL, Santander, Spain.
11
Public Health Division of Gipuzkoa, Biodonostia Research Institute, San Sebastian, Spain.
12
Navarra Public Health Institute, Pamplona, Spain.
13
IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
14
University Institute of Oncology of Asturias (IUOPA), Universidad de Oviedo, Oviedo, Spain.
15
Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Hospitales Universitarios de Granada/ University of Granada, Granada, Spain.
16
Department of Preventive Medicine and Public Health, Faculty of Medicine, University of Granada, Granada, Spain.
17
Cancer and Public Health Area, FISABIO - Public Health, Valencia, Spain.
18
General Directorate Public Health, Valencia, Spain.
19
Centro de Investigación en Recursos Naturales, Salud, y Medio Ambiente (RENSMA), University of Huelva, Huelva, Spain.
20
Barcelonaβeta Brain Research Center - Pasqual Maragall Foundation, Barcelona, Spain.
21
CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain.
22
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
23
Department of Pharmacy, Complejo Asistencial Universitario de León, León, Spain.
24
Department of General and Gastrointestinal Surgery, Complejo Asistencial Universitario de León, León, Spain.
25
Dirección General de Salud Pública, Consejería de Sanidad de la Comunidad de Madrid, Madrid, Spain.
26
Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO) and ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain. v.moreno@iconcologia.net.
27
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. v.moreno@iconcologia.net.
28
Department of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain. v.moreno@iconcologia.net.

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 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.

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