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dc.contributor.authorJohansson, M
dc.contributor.authorCarreras-Torres, R
dc.contributor.authorScelo, G
dc.contributor.authorPurdue, MP
dc.contributor.authorMariosa, D
dc.contributor.authorMuller, DC
dc.contributor.authorTimpson, NJ
dc.contributor.authorHaycock, PC
dc.contributor.authorBrown, KM
dc.contributor.authorWang, Z
dc.contributor.authorYe, Y
dc.contributor.authorHofmann, JN
dc.contributor.authorFoll, M
dc.contributor.authorGaborieau, V
dc.contributor.authorMachiela, MJ
dc.contributor.authorColli, LM
dc.contributor.authorLi, P
dc.contributor.authorGarnier, J-G
dc.contributor.authorBlanche, H
dc.contributor.authorBoland, A
dc.contributor.authorBurdette, L
dc.contributor.authorProkhortchouk, E
dc.contributor.authorSkryabin, KG
dc.contributor.authorYeager, M
dc.contributor.authorRadojevic-Skodric, S
dc.contributor.authorOgnjanovic, S
dc.contributor.authorForetova, L
dc.contributor.authorHolcatova, I
dc.contributor.authorJanout, V
dc.contributor.authorMates, D
dc.contributor.authorMukeriya, A
dc.contributor.authorRascu, S
dc.contributor.authorZaridze, D
dc.contributor.authorBencko, V
dc.contributor.authorCybulski, C
dc.contributor.authorFabianova, E
dc.contributor.authorJinga, V
dc.contributor.authorLissowska, J
dc.contributor.authorLubinski, J
dc.contributor.authorNavratilova, M
dc.contributor.authorRudnai, P
dc.contributor.authorBenhamou, S
dc.contributor.authorCancel-Tassin, G
dc.contributor.authorCussenot, O
dc.contributor.authorWeiderpass, E
dc.contributor.authorLjungberg, B
dc.contributor.authorTumkur Sitaram, R
dc.contributor.authorHäggström, C
dc.contributor.authorBruinsma, F
dc.contributor.authorJordan, SJ
dc.contributor.authorSeveri, G
dc.contributor.authorWinship, I
dc.contributor.authorHveem, K
dc.contributor.authorVatten, LJ
dc.contributor.authorFletcher, T
dc.contributor.authorLarsson, SC
dc.contributor.authorWolk, A
dc.contributor.authorBanks, RE
dc.contributor.authorSelby, PJ
dc.contributor.authorEaston, DF
dc.contributor.authorAndreotti, G
dc.contributor.authorBeane Freeman, LE
dc.contributor.authorKoutros, S
dc.contributor.authorMännistö, S
dc.contributor.authorWeinstein, S
dc.contributor.authorClark, PE
dc.contributor.authorEdwards, TL
dc.contributor.authorLipworth, L
dc.contributor.authorGapstur, SM
dc.contributor.authorStevens, VL
dc.contributor.authorCarol, H
dc.contributor.authorFreedman, ML
dc.contributor.authorPomerantz, MM
dc.contributor.authorCho, E
dc.contributor.authorWilson, KM
dc.contributor.authorGaziano, JM
dc.contributor.authorSesso, HD
dc.contributor.authorFreedman, ND
dc.contributor.authorParker, AS
dc.contributor.authorEckel-Passow, JE
dc.contributor.authorHuang, W-Y
dc.contributor.authorKahnoski, RJ
dc.contributor.authorLane, BR
dc.contributor.authorNoyes, SL
dc.contributor.authorPetillo, D
dc.contributor.authorTeh, BT
dc.contributor.authorPeters, U
dc.contributor.authorWhite, E
dc.contributor.authorAnderson, GL
dc.contributor.authorJohnson, L
dc.contributor.authorLuo, J
dc.contributor.authorBuring, J
dc.contributor.authorLee, I-M
dc.contributor.authorChow, W-H
dc.contributor.authorMoore, LE
dc.contributor.authorEisen, T
dc.contributor.authorHenrion, M
dc.contributor.authorLarkin, J
dc.contributor.authorBarman, P
dc.contributor.authorLeibovich, BC
dc.contributor.authorChoueiri, TK
dc.contributor.authorLathrop, GM
dc.contributor.authorDeleuze, J-F
dc.contributor.authorGunter, M
dc.contributor.authorMcKay, JD
dc.contributor.authorWu, X
dc.contributor.authorHoulston, RS
dc.contributor.authorChanock, SJ
dc.contributor.authorRelton, C
dc.contributor.authorRichards, JB
dc.contributor.authorMartin, RM
dc.contributor.authorDavey Smith, G
dc.contributor.authorBrennan, P
dc.date.accessioned2020-06-11T12:39:53Z
dc.date.issued2019-01-03
dc.identifier.citationPLoS medicine, 2019, 16 (1), pp. e1002724 - ?
dc.identifier.issn1549-1277
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3728
dc.identifier.eissn1549-1676
dc.identifier.doi10.1371/journal.pmed.1002724
dc.description.abstractBackground Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findings Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40-1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.Conclusions This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
dc.formatElectronic-eCollection
dc.format.extente1002724 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectCarcinoma, Renal Cell
dc.subjectKidney Neoplasms
dc.subjectDiabetes Mellitus, Type 2
dc.subjectObesity
dc.subjectInsulin
dc.subjectBlood Glucose
dc.subjectLipids
dc.subjectGenetic Markers
dc.subjectBody Mass Index
dc.subjectRisk Factors
dc.subjectBlood Pressure
dc.subjectFemale
dc.subjectMale
dc.subjectGenome-Wide Association Study
dc.subjectMendelian Randomization Analysis
dc.titleThe influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study.
dc.typeJournal Article
dcterms.dateAccepted2018-12-07
rioxxterms.versionofrecord10.1371/journal.pmed.1002724
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-01-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfPLoS medicine
pubs.issue1
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume16
pubs.embargo.termsNot known
icr.researchteamMelanoma and Kidney Canceren_US
icr.researchteamCancer Genomicsen_US
dc.contributor.icrauthorLarkin, Jamesen
dc.contributor.icrauthorHoulston, Richarden


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