title: Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.
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.
authors.affiliation: Department of Gerontology and Geriatrics, C-2-R Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, the Netherlands. s.trompet@lumc.nl
authors.forename: Stella
authors.initials: S
authors.lastname: Trompet
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.forename: Martijn B
authors.initials: MB
authors.lastname: Katan
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Blauw
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.forename: Brendan
authors.initials: B
authors.lastname: Buckley
authors.forename: Muriel
authors.initials: M
authors.lastname: Caslake
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.forename: Jim
authors.initials: J
authors.lastname: Shepherd
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053329:Apolipoprotein E2 / Q000235:genetics; D053318:Apolipoprotein E3 / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D016001:Confidence Intervals; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D057182:Mendelian Randomization Analysis; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D002784:Cholesterol