Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.
Trompet, Stella Jukema, J Wouter Katan, Martijn B Blauw, Gerard J Sattar, Naveed Buckley, Brendan Caslake, Muriel Ford, Ian Shepherd, Jim Westendorp, Rudi G J
Trompet, Stella
Jukema, J Wouter
Katan, Martijn B
Blauw, Gerard J
Sattar, Naveed
Buckley, Brendan
Caslake, Muriel
Ford, Ian
Shepherd, Jim
Westendorp, Rudi G J
Advisors
Editors
Other Contributors
Date
2009-12-01
Date Submitted
Keywords
Other Subjects
Subject Mesh
Aged
Aged, 80 and over
Apolipoprotein E2
Apolipoprotein E3
Apolipoprotein E4
Apolipoproteins E
Cholesterol
Confidence Intervals
Female
Genotype
Humans
Linear Models
Male
Mendelian Randomization Analysis
Neoplasms
Proportional Hazards Models
Prospective Studies
Risk Factors
Aged, 80 and over
Apolipoprotein E2
Apolipoprotein E3
Apolipoprotein E4
Apolipoproteins E
Cholesterol
Confidence Intervals
Female
Genotype
Humans
Linear Models
Male
Mendelian Randomization Analysis
Neoplasms
Proportional Hazards Models
Prospective Studies
Risk Factors
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
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.
Language
en
ISSN
1476-6256
eISSN
ISBN
DOI
10.1093/aje/kwp294
PMID
19889709