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dc.contributor.authorBull, CJ
dc.contributor.authorBonilla, C
dc.contributor.authorHolly, JMP
dc.contributor.authorPerks, CM
dc.contributor.authorDavies, N
dc.contributor.authorHaycock, P
dc.contributor.authorYu, OHY
dc.contributor.authorRichards, JB
dc.contributor.authorEeles, R
dc.contributor.authorEaston, D
dc.contributor.authorKote-Jarai, Z
dc.contributor.authorAmin Al Olama, A
dc.contributor.authorBenlloch, S
dc.contributor.authorMuir, K
dc.contributor.authorGiles, GG
dc.contributor.authorMacInnis, RJ
dc.contributor.authorWiklund, F
dc.contributor.authorGronberg, H
dc.contributor.authorHaiman, CA
dc.contributor.authorSchleutker, J
dc.contributor.authorNordestgaard, BG
dc.contributor.authorTravis, RC
dc.contributor.authorNeal, D
dc.contributor.authorPashayan, N
dc.contributor.authorKhaw, K-T
dc.contributor.authorStanford, JL
dc.contributor.authorBlot, WJ
dc.contributor.authorThibodeau, S
dc.contributor.authorMaier, C
dc.contributor.authorKibel, AS
dc.contributor.authorCybulski, C
dc.contributor.authorCannon-Albright, L
dc.contributor.authorBrenner, H
dc.contributor.authorPark, J
dc.contributor.authorKaneva, R
dc.contributor.authorBatra, J
dc.contributor.authorTeixeira, MR
dc.contributor.authorMicheal, A
dc.contributor.authorPandha, H
dc.contributor.authorSmith, GD
dc.contributor.authorLewis, SJ
dc.contributor.authorMartin, RM
dc.contributor.authorPRACTICAL consortium
dc.date.accessioned2018-10-18T10:16:22Z
dc.date.issued2016-06
dc.identifier.citationCancer medicine, 2016, 5 (6), pp. 1125 - 1136
dc.identifier.issn2045-7634
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2902
dc.identifier.eissn2045-7634
dc.identifier.doi10.1002/cam4.695
dc.description.abstractGenetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL consortium were analyzed. Allele scores based on single nucleotide polymorphisms (SNPs) previously reported to be uniquely associated with each of low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels, were first validated in an independent dataset, and then entered into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL, comparing high- (≥7 Gleason score) versus low-grade (<7 Gleason score) cancers was 1.50 (95% CI: 0.92, 2.46; P = 0.11). A genetically instrumented SD increase in TGs was weakly associated with stage: the OR for advanced versus localized cancer per unit increase in genetic risk score was 1.68 (95% CI: 0.95, 3.00; P = 0.08). The rs12916-T variant in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk. We found weak evidence that higher LDL and TG levels increase aggressive prostate cancer risk, and that a variant in HMGCR (that mimics the LDL lowering effect of statin drugs) reduces risk. However, inferences are limited by sample size and evidence of pleiotropy.
dc.formatPrint-Electronic
dc.format.extent1125 - 1136
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectPRACTICAL consortium
dc.subjectHumans
dc.subjectProstatic Neoplasms
dc.subjectGenetic Predisposition to Disease
dc.subjectLipids
dc.subjectNeoplasm Staging
dc.subjectPopulation Surveillance
dc.subjectOdds Ratio
dc.subjectCase-Control Studies
dc.subjectQuantitative Trait, Heritable
dc.subjectPolymorphism, Single Nucleotide
dc.subjectMale
dc.subjectMeta-Analysis as Topic
dc.subjectGenetic Variation
dc.subjectGenome-Wide Association Study
dc.subjectGenetic Association Studies
dc.subjectMendelian Randomization Analysis
dc.subjectNeoplasm Grading
dc.titleBlood lipids and prostate cancer: a Mendelian randomization analysis.
dc.typeJournal Article
dcterms.dateAccepted2016-02-08
rioxxterms.versionofrecord10.1002/cam4.695
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer medicine
pubs.issue6
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.publication-statusPublished
pubs.volume5
pubs.embargo.termsNot known
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorEeles, Rosalinden
dc.contributor.icrauthorKote-Jarai, Zsofiaen


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