Apolipoprotein e genotype, plasma cholesterol, and cancer: A mendelian randomization study

Stella Trompet, J. Wouter Jukema, Martijn B. Katan, Gerard J. Blauw, Naveed Sattar, Brendan Buckley, Muriel Caslake, Ian Ford, Jim Shepherd, Rudi G.J. Westendorp, Anton J.M. De Craen

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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.

Original languageEnglish
Pages (from-to)1415-1421
Number of pages7
JournalAmerican Journal of Epidemiology
Volume170
Issue number11
DOIs
StatePublished - 2009
Externally publishedYes

Keywords

  • Apolipoproteins E
  • Cholesterol
  • Genetics
  • Neoplasms
  • Random allocation

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