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dc.contributor.authorBonilla, C
dc.contributor.authorLewis, SJ
dc.contributor.authorRowlands, M-A
dc.contributor.authorGaunt, TR
dc.contributor.authorDavey Smith, G
dc.contributor.authorGunnell, D
dc.contributor.authorPalmer, T
dc.contributor.authorDonovan, JL
dc.contributor.authorHamdy, FC
dc.contributor.authorNeal, DE
dc.contributor.authorEeles, R
dc.contributor.authorEaston, D
dc.contributor.authorKote-Jarai, Z
dc.contributor.authorAl Olama, AA
dc.contributor.authorBenlloch, S
dc.contributor.authorMuir, K
dc.contributor.authorGiles, GG
dc.contributor.authorWiklund, F
dc.contributor.authorGrönberg, H
dc.contributor.authorHaiman, CA
dc.contributor.authorSchleutker, J
dc.contributor.authorNordestgaard, BG
dc.contributor.authorTravis, RC
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.authorPandha, H
dc.contributor.authorPRACTICAL consortium
dc.contributor.authorLathrop, M
dc.contributor.authorMartin, RM
dc.contributor.authorHolly, JMP
dc.date.accessioned2016-11-23T10:50:48Z
dc.date.issued2016-10
dc.identifier.citationInternational journal of cancer, 2016, 139 (7), pp. 1520 - 1533
dc.identifier.issn0020-7136
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/230
dc.identifier.eissn1097-0215
dc.identifier.doi10.1002/ijc.30206
dc.description.abstractCirculating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs. high (≥ 7) Gleason grade, localised vs. advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs. low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker.
dc.formatPrint-Electronic
dc.format.extent1520 - 1533
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectPRACTICAL consortium
dc.subjectHumans
dc.subjectProstatic Neoplasms
dc.subjectSomatomedins
dc.subjectInsulin-Like Growth Factor Binding Proteins
dc.subjectNeoplasm Staging
dc.subjectCase-Control Studies
dc.subjectLongitudinal Studies
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectMale
dc.subjectGenome-Wide Association Study
dc.subjectMendelian Randomization Analysis
dc.subjectNeoplasm Grading
dc.subjectUnited Kingdom
dc.titleAssessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels.
dc.typeJournal Article
dcterms.dateAccepted2016-04-07
rioxxterms.versionofrecord10.1002/ijc.30206
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfInternational journal of cancer
pubs.issue7
pubs.notesNo embargo
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.volume139
pubs.embargo.termsNo embargo
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorEeles, Rosalinden
dc.contributor.icrauthorKote-Jarai, Zsofiaen


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