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dc.contributor.authorRodriguez-Broadbent, Hen_US
dc.contributor.authorLaw, PJen_US
dc.contributor.authorSud, Aen_US
dc.contributor.authorPalin, Ken_US
dc.contributor.authorTuupanen, Sen_US
dc.contributor.authorGylfe, Aen_US
dc.contributor.authorHänninen, UAen_US
dc.contributor.authorCajuso, Ten_US
dc.contributor.authorTanskanen, Ten_US
dc.contributor.authorKondelin, Jen_US
dc.contributor.authorKaasinen, Een_US
dc.contributor.authorSarin, A-Pen_US
dc.contributor.authorRipatti, Sen_US
dc.contributor.authorEriksson, JGen_US
dc.contributor.authorRissanen, Hen_US
dc.contributor.authorKnekt, Pen_US
dc.contributor.authorPukkala, Een_US
dc.contributor.authorJousilahti, Pen_US
dc.contributor.authorSalomaa, Ven_US
dc.contributor.authorPalotie, Aen_US
dc.contributor.authorRenkonen-Sinisalo, Len_US
dc.contributor.authorLepistö, Aen_US
dc.contributor.authorBöhm, Jen_US
dc.contributor.authorMecklin, J-Pen_US
dc.contributor.authorAl-Tassan, NAen_US
dc.contributor.authorPalles, Cen_US
dc.contributor.authorMartin, Len_US
dc.contributor.authorBarclay, Een_US
dc.contributor.authorFarrington, SMen_US
dc.contributor.authorTimofeeva, MNen_US
dc.contributor.authorMeyer, BFen_US
dc.contributor.authorWakil, SMen_US
dc.contributor.authorCampbell, Hen_US
dc.contributor.authorSmith, CGen_US
dc.contributor.authorIdziaszczyk, Sen_US
dc.contributor.authorMaughan, TSen_US
dc.contributor.authorKaplan, Ren_US
dc.contributor.authorKerr, Ren_US
dc.contributor.authorKerr, Den_US
dc.contributor.authorPassarelli, MNen_US
dc.contributor.authorFigueiredo, JCen_US
dc.contributor.authorBuchanan, DDen_US
dc.contributor.authorWin, AKen_US
dc.contributor.authorHopper, JLen_US
dc.contributor.authorJenkins, MAen_US
dc.contributor.authorLindor, NMen_US
dc.contributor.authorNewcomb, PAen_US
dc.contributor.authorGallinger, Sen_US
dc.contributor.authorConti, Den_US
dc.contributor.authorSchumacher, Fen_US
dc.contributor.authorCasey, Gen_US
dc.contributor.authorAaltonen, LAen_US
dc.contributor.authorCheadle, JPen_US
dc.contributor.authorTomlinson, IPen_US
dc.contributor.authorDunlop, MGen_US
dc.contributor.authorHoulston, RSen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2017-04-07T15:05:07Z
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28340513en_US
dc.identifier.citationInt J Cancer, 140 (12), pp. 2701 - 2708en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/567
dc.identifier.eissn1097-0215en_US
dc.identifier.doi10.1002/ijc.30709en_US
dc.description.abstractWhile elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP-CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20-1.79, p = 1.68 × 10-4 ). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92-1.18, p = 0.49), 0.94 (95% CI: 0.84-1.05, p = 0.27), and 0.98 (95% CI: 0.85-1.12, p = 0.75) respectively. A genetic risk score for 3-hydoxy-3-methylglutaryl-coenzyme A reductase (HMGCR) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR = 0.69, 95% CI: 0.49-0.99, p = 0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia.en_US
dc.format.extent2701 - 2708en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.subjectMendelian randomisationen_US
dc.subjectcholesterolen_US
dc.subjectcolorectal canceren_US
dc.subjecthyperlipidaemiaen_US
dc.subjectrisken_US
dc.subjectCholesterolen_US
dc.subjectColorectal Neoplasmsen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectGenome-Wide Association Studyen_US
dc.subjectHumansen_US
dc.subjectHyperlipidemiasen_US
dc.subjectLipoproteins, HDLen_US
dc.subjectLipoproteins, LDLen_US
dc.subjectLogistic Modelsen_US
dc.subjectMendelian Randomization Analysisen_US
dc.subjectOdds Ratioen_US
dc.subjectPolymorphism, Single Nucleotideen_US
dc.subjectRisk Assessmenten_US
dc.subjectRisk Factorsen_US
dc.subjectTriglyceridesen_US
dc.titleMendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-02-08en_US
rioxxterms.versionofrecord10.1002/ijc.30709en_US
rioxxterms.licenseref.startdate2017-02-08en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfInt J Canceren_US
pubs.issue12en_US
pubs.notesNot knownen_US
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/Molecular & Population Genetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics
pubs.publication-statusPublisheden_US
pubs.volume140en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMolecular & Population Geneticsen_US
dc.contributor.icrauthorHoulston, Richarden_US
dc.contributor.icrauthorLaw, Philipen_US
dc.contributor.icrauthorSud, Amiten_US


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