Apolipoprotein E genotype, plasma cholesterol, and cancer: a mendelian randomization study

Trompet, S. et al. (2009) Apolipoprotein E genotype, plasma cholesterol, and cancer: a mendelian randomization study. American Journal of Epidemiology, 170(11), pp. 1415-1421. (doi:10.1093/aje/kwp294)

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Abstract

Observational studies have shown an association between low plasma cholesterol levels and increased risk of cancer, whereas most randomized clinical trials involving cholesterol-lowering medications have not shown this association. Between 1997 and 2002, the authors assessed the association between plasma cholesterol levels and cancer risk, free from confounding and reverse causality, in a Mendelian randomization study using apolipoprotein E (ApoE) genotype. ApoE genotype, plasma cholesterol levels, and cancer incidence and mortality were measured during a 3-year follow-up period among 2,913 participants in the Prospective Study of Pravastatin in the Elderly at Risk. Subjects within the lowest third of plasma cholesterol level at baseline had increased risks of cancer incidence (hazard ratio (HR) = 1.90, 95% confidence interval (CI): 1.34, 2.70) and cancer mortality (HR = 2.03, 95% CI: 1.23, 3.34) relative to subjects within the highest third of plasma cholesterol. However, carriers of the ApoE2 genotype (n = 332), who had 9% lower plasma cholesterol levels than carriers of the ApoE4 genotype (n = 635), did not have increased risk of cancer incidence (HR = 0.86, 95% CI: 0.50, 1.47) or cancer mortality (HR = 0.70, 95% CI: 0.30, 1.60) compared with ApoE4 carriers. These findings suggest that low cholesterol levels are not causally related to increased cancer risk.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Caslake, Professor Muriel and Ford, Professor Ian and Shepherd, Prof James and Sattar, Professor Naveed
Authors: Trompet, S., Jukema, J.W., Katan, M.B., Blauw, G.J., Sattar, N.A., Buckley, B., Caslake, M., Ford, I., Shepherd, J., Westendorp, R.G.J., and de Craen, A.J.M.
Subjects:R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
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Journal Name:American Journal of Epidemiology
ISSN:0002-9262
ISSN (Online):1476-6256
Published Online:04 November 2009

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