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dc.contributor.authorJohansson, Mattias
dc.contributor.authorCarreras-Torres, Robert
dc.contributor.authorScelo, Ghislaine
dc.contributor.authorPurdue, Mark P.
dc.contributor.authorMariosa, Daniela
dc.contributor.authorMuller, David C.
dc.contributor.authorTimpson, Nicholas J.
dc.contributor.authorHaycock, Philip C.
dc.contributor.authorBrown, Kevin M.
dc.contributor.authorWang, Zhaoming
dc.contributor.authorYe, Yuanqing
dc.contributor.authorHofmann, Jonathan N.
dc.contributor.authorFoll, Matthieu
dc.contributor.authorGaborieau, Valerie
dc.contributor.authorMachiela, Mitchell J.
dc.contributor.authorColli, Leandro M.
dc.contributor.authorLi, Peng
dc.contributor.authorGarnier, Jean-Guillaume
dc.contributor.authorBlanche, Helene
dc.contributor.authorBoland, Anne
dc.contributor.authorBurdette, Laurie
dc.contributor.authorProkhortchouk, Egor
dc.contributor.authorSkryabin, Konstantin G.
dc.contributor.authorYeager, Meredith
dc.contributor.authorRadojevic-Skodric, Sanja
dc.contributor.authorOgnjanovic, Simona
dc.contributor.authorForetova, Lenka
dc.contributor.authorHolcatova, Ivana
dc.contributor.authorJanout, Vladimir
dc.contributor.authorMates, Dana
dc.contributor.authorMukeriya, Anush
dc.contributor.authorRascu, Stefan
dc.contributor.authorZaridze, David
dc.contributor.authorBencko, Vladimir
dc.contributor.authorCybulski, Cezary
dc.contributor.authorFabianova, Eleonora
dc.contributor.authorJinga, Viorel
dc.contributor.authorLissowska, Jolanta
dc.contributor.authorLubinski, Jan
dc.contributor.authorNavratilova, Marie
dc.contributor.authorRudnai, Peter
dc.contributor.authorBenhamou, Simone
dc.contributor.authorCancel-Tassin, Geraldine
dc.contributor.authorCussenot, Olivier
dc.contributor.authorWeiderpass, Elisabete
dc.contributor.authorLjungberg, Börje
dc.contributor.authorTumkur Sitaram, Raviprakash
dc.contributor.authorHäggström, Christel
dc.contributor.authorBruinsma, Fiona
dc.contributor.authorJordan, Susan J.
dc.contributor.authorSeveri, Gianluca
dc.contributor.authorWinship, Ingrid
dc.contributor.authorHveem, Kristian
dc.contributor.authorVatten, Lars Johan
dc.contributor.authorFletcher, Tony
dc.contributor.authorLarsson, Susanna C.
dc.contributor.authorWolk, Alicja
dc.contributor.authorBanks, Rosamonde E.
dc.contributor.authorSelby, Peter J.
dc.contributor.authorEaston, Douglas F.
dc.contributor.authorAndreotti, Gabriella
dc.contributor.authorBeane Freeman, Laura E.
dc.contributor.authorKoutros, Stella
dc.contributor.authorMännistö, Satu
dc.contributor.authorWeinstein, Stephanie
dc.contributor.authorClark, Peter E.
dc.contributor.authorEdwards, Todd L.
dc.contributor.authorLipworth, Loren
dc.contributor.authorGapstur, Susan M.
dc.contributor.authorStevens, Victoria L.
dc.contributor.authorCarol, Hallie
dc.contributor.authorFreedman, Matthew L.
dc.contributor.authorPomerantz, Mark M.
dc.contributor.authorCho, Eunyoung
dc.contributor.authorWilson, Kathryn M.
dc.contributor.authorGaziano, J. Michael
dc.contributor.authorSesso, Howard D.
dc.contributor.authorFreedman, Neal D.
dc.contributor.authorParker, Alexander S.
dc.contributor.authorEckel-Passow, Jeanette E.
dc.contributor.authorHuang, Wen-Yi
dc.contributor.authorKahnoski, Richard J.
dc.contributor.authorLane, Brian R.
dc.contributor.authorNoyes, Sabrina L.
dc.contributor.authorPetillo, David
dc.contributor.authorTeh, Bin Tean
dc.contributor.authorPeters, Ulrike
dc.contributor.authorWhite, Emily
dc.contributor.authorAnderson, Garnet L.
dc.contributor.authorJohnson, Lisa
dc.contributor.authorLuo, Juhua
dc.contributor.authorBuring, Julie
dc.contributor.authorLee, I-Min
dc.contributor.authorChow, Wong-Ho
dc.contributor.authorMoore, Lee E.
dc.contributor.authorEisen, Timothy
dc.contributor.authorHenrion, Marc
dc.contributor.authorLarkin, James
dc.contributor.authorBarman, Poulami
dc.contributor.authorLeibovich, Bradley C.
dc.contributor.authorChoueiri, Toni K.
dc.contributor.authorLathrop, G. Mark
dc.contributor.authorDeleuze, Jean-François
dc.contributor.authorGunter, Marc
dc.contributor.authorMcKay, James D.
dc.contributor.authorWu, Xifeng
dc.contributor.authorHoulston, Richard S.
dc.contributor.authorChanock, Stephen J.
dc.contributor.authorRelton, Caroline
dc.contributor.authorRichards, J. Brent
dc.contributor.authorMartin, Richard M.
dc.contributor.authorDavey Smith, George
dc.contributor.authorBrennan, Paul
dc.date.accessioned2020-03-09T14:13:18Z
dc.date.available2020-03-09T14:13:18Z
dc.date.issued2019-01-03
dc.description.abstract<i>Background</i> - 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.<p> <p><i>Methods and findings</i> - 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 (OR<sub>SD</sub>) 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 (OR<sub>SD</sub>: 1.63, 95% CI 1.40–1.90) and body fat percentage (OR<sub>SD</sub>: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (OR<sub>SD</sub>: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; OR<sub>SD</sub>: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (OR<sub>SD</sub>: 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.<p> <p><i>Conclusions</i> - 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.en_US
dc.identifier.citationJohansson, M., Carreras-Torres, R., Scelo, G., Purdue, M.P., Mariosa, D., Muller, D.C. ... Brennan, P. (2019). The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study. <i>Plos Medicine, 16</i>(1): e1002724.en_US
dc.identifier.cristinIDFRIDAID 1690521
dc.identifier.doi10.1371/journal.pmed.1002724
dc.identifier.issn1548-7091
dc.identifier.issn1548-7105
dc.identifier.urihttps://hdl.handle.net/10037/17685
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.journalNature Methods
dc.relation.projectIDStiftelsen Kristian Gerhard Jebsen: SKGJ-MED-015en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2019 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700en_US
dc.subjectVDP::Medisinske Fag: 700en_US
dc.titleThe influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization studyen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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