Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.
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.
Trompet
Stella
S
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
Jukema
J Wouter
JW
Katan
Martijn B
MB
Blauw
Gerard J
GJ
Sattar
Naveed
N
Buckley
Brendan
B
Caslake
Muriel
M
Ford
Ian
I
Shepherd
Jim
J
Westendorp
Rudi G J
RG
de Craen
Anton J M
AJ
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
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D002784:Cholesterol