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Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause

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.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Sci Rep. 2019 Sep 16;9(1):13407

Editorial: Nature Publishing Group

 Año de publicación: 2019

Nº de páginas: 9

Tipo de publicación: Artículo de Revista

 DOI: 10.1038/s41598-019-49880-w

ISSN: 2045-2322

Url de la publicación: https://doi.org/10.1038/s41598-019-49880-w

Autores/as

IBÁÑEZ-SANZ, GEMMA

DÍEZ-VILLANUEVA, ANNA

RIERA-PONSATI, MARINA

FERNÁNDEZ- VILLA, TANIA

FERNÁNDEZ NAVARRO, PABLO

BUSTAMANTE, MARIONA

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, CAMILO

ALTZIBAR, JONE M.

ARDANAZ, EVA