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dc.contributor.authorTelomeres Mendelian Randomization Collaboration
dc.contributor.authorHaycock, PC
dc.contributor.authorBurgess, S
dc.contributor.authorNounu, A
dc.contributor.authorZheng, J
dc.contributor.authorOkoli, GN
dc.contributor.authorBowden, J
dc.contributor.authorWade, KH
dc.contributor.authorTimpson, NJ
dc.contributor.authorEvans, DM
dc.contributor.authorWilleit, P
dc.contributor.authorAviv, A
dc.contributor.authorGaunt, TR
dc.contributor.authorHemani, G
dc.contributor.authorMangino, M
dc.contributor.authorEllis, HP
dc.contributor.authorKurian, KM
dc.contributor.authorPooley, KA
dc.contributor.authorEeles, RA
dc.contributor.authorLee, JE
dc.contributor.authorFang, S
dc.contributor.authorChen, WV
dc.contributor.authorLaw, MH
dc.contributor.authorBowdler, LM
dc.contributor.authorIles, MM
dc.contributor.authorYang, Q
dc.contributor.authorWorrall, BB
dc.contributor.authorMarkus, HS
dc.contributor.authorHung, RJ
dc.contributor.authorAmos, CI
dc.contributor.authorSpurdle, AB
dc.contributor.authorThompson, DJ
dc.contributor.authorO'Mara, TA
dc.contributor.authorWolpin, B
dc.contributor.authorAmundadottir, L
dc.contributor.authorStolzenberg-Solomon, R
dc.contributor.authorTrichopoulou, A
dc.contributor.authorOnland-Moret, NC
dc.contributor.authorLund, E
dc.contributor.authorDuell, EJ
dc.contributor.authorCanzian, F
dc.contributor.authorSeveri, G
dc.contributor.authorOvervad, K
dc.contributor.authorGunter, MJ
dc.contributor.authorTumino, R
dc.contributor.authorSvenson, U
dc.contributor.authorvan Rij, A
dc.contributor.authorBaas, AF
dc.contributor.authorBown, MJ
dc.contributor.authorSamani, NJ
dc.contributor.authorvan t'Hof, FNG
dc.contributor.authorTromp, G
dc.contributor.authorJones, GT
dc.contributor.authorKuivaniemi, H
dc.contributor.authorElmore, JR
dc.contributor.authorJohansson, M
dc.contributor.authorMckay, J
dc.contributor.authorScelo, G
dc.contributor.authorCarreras-Torres, R
dc.contributor.authorGaborieau, V
dc.contributor.authorBrennan, P
dc.contributor.authorBracci, PM
dc.contributor.authorNeale, RE
dc.contributor.authorOlson, SH
dc.contributor.authorGallinger, S
dc.contributor.authorLi, D
dc.contributor.authorPetersen, GM
dc.contributor.authorRisch, HA
dc.contributor.authorKlein, AP
dc.contributor.authorHan, J
dc.contributor.authorAbnet, CC
dc.contributor.authorFreedman, ND
dc.contributor.authorTaylor, PR
dc.contributor.authorMaris, JM
dc.contributor.authorAben, KK
dc.contributor.authorKiemeney, LA
dc.contributor.authorVermeulen, SH
dc.contributor.authorWiencke, JK
dc.contributor.authorWalsh, KM
dc.contributor.authorWrensch, M
dc.contributor.authorRice, T
dc.contributor.authorTurnbull, C
dc.contributor.authorLitchfield, K
dc.contributor.authorPaternoster, L
dc.contributor.authorStandl, M
dc.contributor.authorAbecasis, GR
dc.contributor.authorSanGiovanni, JP
dc.contributor.authorLi, Y
dc.contributor.authorMijatovic, V
dc.contributor.authorSapkota, Y
dc.contributor.authorLow, S-K
dc.contributor.authorZondervan, KT
dc.contributor.authorMontgomery, GW
dc.contributor.authorNyholt, DR
dc.contributor.authorvan Heel, DA
dc.contributor.authorHunt, K
dc.contributor.authorArking, DE
dc.contributor.authorAshar, FN
dc.contributor.authorSotoodehnia, N
dc.contributor.authorWoo, D
dc.contributor.authorRosand, J
dc.contributor.authorComeau, ME
dc.contributor.authorBrown, WM
dc.contributor.authorSilverman, EK
dc.contributor.authorHokanson, JE
dc.contributor.authorCho, MH
dc.contributor.authorHui, J
dc.contributor.authorFerreira, MA
dc.contributor.authorThompson, PJ
dc.contributor.authorMorrison, AC
dc.contributor.authorFelix, JF
dc.contributor.authorSmith, NL
dc.contributor.authorChristiano, AM
dc.contributor.authorPetukhova, L
dc.contributor.authorBetz, RC
dc.contributor.authorFan, X
dc.contributor.authorZhang, X
dc.contributor.authorZhu, C
dc.contributor.authorLangefeld, CD
dc.contributor.authorThompson, SD
dc.contributor.authorWang, F
dc.contributor.authorLin, X
dc.contributor.authorSchwartz, DA
dc.contributor.authorFingerlin, T
dc.contributor.authorRotter, JI
dc.contributor.authorCotch, MF
dc.contributor.authorJensen, RA
dc.contributor.authorMunz, M
dc.contributor.authorDommisch, H
dc.contributor.authorSchaefer, AS
dc.contributor.authorHan, F
dc.contributor.authorOllila, HM
dc.contributor.authorHillary, RP
dc.contributor.authorAlbagha, O
dc.contributor.authorRalston, SH
dc.contributor.authorZeng, C
dc.contributor.authorZheng, W
dc.contributor.authorShu, X-O
dc.contributor.authorReis, A
dc.contributor.authorUebe, S
dc.contributor.authorHüffmeier, U
dc.contributor.authorKawamura, Y
dc.contributor.authorOtowa, T
dc.contributor.authorSasaki, T
dc.contributor.authorHibberd, ML
dc.contributor.authorDavila, S
dc.contributor.authorXie, G
dc.contributor.authorSiminovitch, K
dc.contributor.authorBei, J-X
dc.contributor.authorZeng, Y-X
dc.contributor.authorFörsti, A
dc.contributor.authorChen, B
dc.contributor.authorLandi, S
dc.contributor.authorFranke, A
dc.contributor.authorFischer, A
dc.contributor.authorEllinghaus, D
dc.contributor.authorFlores, C
dc.contributor.authorNoth, I
dc.contributor.authorMa, S-F
dc.contributor.authorFoo, JN
dc.contributor.authorLiu, J
dc.contributor.authorKim, J-W
dc.contributor.authorCox, DG
dc.contributor.authorDelattre, O
dc.contributor.authorMirabeau, O
dc.contributor.authorSkibola, CF
dc.contributor.authorTang, CS
dc.contributor.authorGarcia-Barcelo, M
dc.contributor.authorChang, K-P
dc.contributor.authorSu, W-H
dc.contributor.authorChang, Y-S
dc.contributor.authorMartin, NG
dc.contributor.authorGordon, S
dc.contributor.authorWade, TD
dc.contributor.authorLee, C
dc.contributor.authorKubo, M
dc.contributor.authorCha, P-C
dc.contributor.authorNakamura, Y
dc.contributor.authorLevy, D
dc.contributor.authorKimura, M
dc.contributor.authorHwang, S-J
dc.contributor.authorHunt, S
dc.contributor.authorSpector, T
dc.contributor.authorSoranzo, N
dc.contributor.authorManichaikul, AW
dc.contributor.authorBarr, RG
dc.contributor.authorKahali, B
dc.contributor.authorSpeliotes, E
dc.contributor.authorYerges-Armstrong, LM
dc.contributor.authorCheng, C-Y
dc.contributor.authorJonas, JB
dc.contributor.authorWong, TY
dc.contributor.authorFogh, I
dc.contributor.authorLin, K
dc.contributor.authorPowell, JF
dc.contributor.authorRice, K
dc.contributor.authorRelton, CL
dc.contributor.authorMartin, RM
dc.contributor.authorDavey Smith, G
dc.date.accessioned2017-11-01T16:11:55Z
dc.date.issued2017-05
dc.identifier.citationJAMA oncology, 2017, 3 (5), pp. 636 - 651
dc.identifier.issn2374-2437
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/895
dc.identifier.eissn2374-2445
dc.identifier.doi10.1001/jamaoncol.2016.5945
dc.description.abstractImportance The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation.Objective To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.Data sources Genomewide association studies (GWAS) published up to January 15, 2015.Study selection GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available.Data extraction and synthesis Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.Main outcomes and measures Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.Results Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]).Conclusions and relevance It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
dc.formatPrint
dc.format.extent636 - 651
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectTelomeres Mendelian Randomization Collaboration
dc.subjectTelomere
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectCardiovascular Diseases
dc.subjectGenetic Predisposition to Disease
dc.subjectRisk Assessment
dc.subjectGerm-Line Mutation
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectGenome-Wide Association Study
dc.subjectMendelian Randomization Analysis
dc.subjectTelomere Homeostasis
dc.titleAssociation Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study.
dc.typeJournal Article
dcterms.dateAccepted2016-10-21
rioxxterms.funderThe Institute of Cancer Research
rioxxterms.identifier.projectUnspecified
rioxxterms.versionofrecord10.1001/jamaoncol.2016.5945
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2017-05
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJAMA oncology
pubs.issue5
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/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics
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/Primary Group/Royal Marsden Clinical Units
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/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics
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/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume3
pubs.embargo.termsNot known
icr.researchteamMolecular & Population Geneticsen_US
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorTurnbull, Clareen
dc.contributor.icrauthorEeles, Rosalinden
dc.contributor.icrauthorMarsden,en
dc.contributor.icrauthorLitchfield, Kevinen


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