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dc.contributor.authorBonilla, C
dc.contributor.authorLewis, SJ
dc.contributor.authorMartin, RM
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.authorGronberg, 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.authorLathrop, M
dc.contributor.authorDavey Smith, G
dc.contributor.authorPRACTICAL consortium
dc.date.accessioned2016-11-09T11:41:28Z
dc.date.issued2016-04-04
dc.identifier.citationBMC medicine, 2016, 14 pp. 66 - ?
dc.identifier.issn1741-7015
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/198
dc.identifier.eissn1741-7015
dc.identifier.doi10.1186/s12916-016-0602-x
dc.description.abstractBackground Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain causal estimates, we examined the role of pubertal development in prostate cancer using genetic polymorphisms associated with Tanner stage in adolescent boys in a Mendelian randomization (MR) approach.Methods We derived a weighted genetic risk score for pubertal development, combining 13 SNPs associated with male Tanner stage. A higher score indicated a later puberty onset. We examined the association of this score with prostate cancer risk, stage and grade in the UK-based ProtecT case-control study (n = 2,927), and used the PRACTICAL consortium (n = 43,737) as a replication sample.Results In ProtecT, the puberty genetic score was inversely associated with prostate cancer grade (odds ratio (OR) of high- vs. low-grade cancer, per tertile of the score: 0.76; 95 % CI, 0.64-0.89). In an instrumental variable estimation of the causal OR, later physical development in adolescence (equivalent to a difference of one Tanner stage between pubertal boys of the same age) was associated with a 77 % (95 % CI, 43-91 %) reduced odds of high Gleason prostate cancer. In PRACTICAL, the puberty genetic score was associated with prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95 % CI, 0.91-1.00) and prostate cancer-specific mortality (hazard ratio amongst cases, per tertile: 0.94; 95 % CI, 0.90-0.98), but not with disease grade.Conclusions Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease.
dc.formatElectronic
dc.format.extent66 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectPRACTICAL consortium
dc.subjectHumans
dc.subjectProstatic Neoplasms
dc.subjectNeoplasm Staging
dc.subjectOdds Ratio
dc.subjectRisk Factors
dc.subjectRegression Analysis
dc.subjectSurvival Analysis
dc.subjectCase-Control Studies
dc.subjectRandom Allocation
dc.subjectAge of Onset
dc.subjectPuberty
dc.subjectSexual Maturation
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAdolescent
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectMale
dc.subjectGenome-Wide Association Study
dc.subjectMendelian Randomization Analysis
dc.subjectUnited Kingdom
dc.titlePubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort.
dc.typeJournal Article
dcterms.dateAccepted2016-03-16
rioxxterms.versionofrecord10.1186/s12916-016-0602-x
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-04-04
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBMC medicine
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.volume14
pubs.embargo.termsNo embargo
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorEeles, Rosalinden
dc.contributor.icrauthorKote-Jarai, Zsofiaen


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