Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.

Hdl Handle:
http://hdl.handle.net/10147/200739
Title:
Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.
Authors:
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; de Craen, Anton J M
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
Citation:
Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study. 2009, 170 (11):1415-21 Am. J. Epidemiol.
Journal:
American journal of epidemiology
Issue Date:
1-Dec-2009
URI:
http://hdl.handle.net/10147/200739
DOI:
10.1093/aje/kwp294
PubMed ID:
19889709
Additional Links:
http://aje.oxfordjournals.org/content/170/11/1415.full.pdf+html
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.
Item Type:
Article
Language:
en
Description:
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.
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
ISSN:
1476-6256

Full metadata record

DC FieldValue Language
dc.contributor.authorTrompet, Stellaen
dc.contributor.authorJukema, J Wouteren
dc.contributor.authorKatan, Martijn Ben
dc.contributor.authorBlauw, Gerard Jen
dc.contributor.authorSattar, Naveeden
dc.contributor.authorBuckley, Brendanen
dc.contributor.authorCaslake, Murielen
dc.contributor.authorFord, Ianen
dc.contributor.authorShepherd, Jimen
dc.contributor.authorWestendorp, Rudi G Jen
dc.contributor.authorde Craen, Anton J Men
dc.date.accessioned2012-01-06T15:23:07Z-
dc.date.available2012-01-06T15:23:07Z-
dc.date.issued2009-12-01-
dc.identifier.citationApolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study. 2009, 170 (11):1415-21 Am. J. Epidemiol.en
dc.identifier.issn1476-6256-
dc.identifier.pmid19889709-
dc.identifier.doi10.1093/aje/kwp294-
dc.identifier.urihttp://hdl.handle.net/10147/200739-
dc.descriptionObservational 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.en
dc.description.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.-
dc.language.isoenen
dc.relation.urlhttp://aje.oxfordjournals.org/content/170/11/1415.full.pdf+htmlen
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshApolipoprotein E2-
dc.subject.meshApolipoprotein E3-
dc.subject.meshApolipoprotein E4-
dc.subject.meshApolipoproteins E-
dc.subject.meshCholesterol-
dc.subject.meshConfidence Intervals-
dc.subject.meshFemale-
dc.subject.meshGenotype-
dc.subject.meshHumans-
dc.subject.meshLinear Models-
dc.subject.meshMale-
dc.subject.meshMendelian Randomization Analysis-
dc.subject.meshNeoplasms-
dc.subject.meshProportional Hazards Models-
dc.subject.meshProspective Studies-
dc.subject.meshRisk Factors-
dc.titleApolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.en
dc.typeArticleen
dc.contributor.departmentDepartment of Gerontology and Geriatrics, C-2-R Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, the Netherlands. s.trompet@lumc.nlen
dc.identifier.journalAmerican journal of epidemiologyen
dc.description.provinceMunster-

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