Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.
Jukema, J Wouter
Katan, Martijn B
Blauw, Gerard J
Westendorp, Rudi G J
de Craen, Anton J M
AffiliationDepartment of Gerontology and Geriatrics, C-2-R Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, the Netherlands. firstname.lastname@example.org
Aged, 80 and over
Mendelian Randomization Analysis
Proportional Hazards Models
MetadataShow full item record
CitationApolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study. 2009, 170 (11):1415-21 Am. J. Epidemiol.
JournalAmerican journal of epidemiology
AbstractObservational 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.
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