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The blood metabolom...
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Guida, FlorenceGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
(författare)
The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium
- Artikel/kapitelEngelska2021
Förlag, utgivningsår, omfång ...
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2021-09-20
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Public Library of Science (PLOS),2021
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:umu-188614
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-188614URI
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https://doi.org/10.1371/journal.pmed.1003786DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Background: Excess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI).Methods and findings: We assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case–control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10−8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 × 10−5), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some—but not all—metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., −0.17 SD change [ßBMI] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 × 10−5). BMI was also associated with increased levels of glutamate (ßBMI: 0.12, p = 1.5 × 10−3). While our results were robust across the participating studies, they were limited to study participants of European descent, and it will, therefore, be important to evaluate if our findings can be generalised to populations with different genetic backgrounds.Conclusions: This study suggests a potentially important role of the blood metabolome in kidney cancer aetiology by highlighting a wide range of metabolites associated with the risk of developing kidney cancer and the extent to which changes in levels of these metabolites are driven by BMI - the principal modifiable risk factor of kidney cancer.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Tan, Vanessa Y.MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
(författare)
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Corbin, Laura J.MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
(författare)
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Smith-Byrne, KarlGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
(författare)
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Alcala, KarineGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
(författare)
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Langenberg, ClaudiaMRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom
(författare)
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Stewart, Isobel D.MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom
(författare)
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Butterworth, Adam S.British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, United Kingdom; Health Data Research UK Cambridge, Wellcome Genome Campus, University of Cambridge, Cambridge, United Kingdom; National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, United Kingdom
(författare)
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Surendran, PraveenBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, United Kingdom; Health Data Research UK Cambridge, Wellcome Genome Campus, University of Cambridge, Cambridge, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
(författare)
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Achaintre, DavidNutrition and Metabolism Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
(författare)
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Adamski, JerzyInstitute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany; Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Experimental Genetics, School of Life Science, Weihenstephan, Technische Universität München, Freising, Germany; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
(författare)
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Exezarreta, Pilar AmianoPublic Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
(författare)
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Bergmann, Manuela M.German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
(författare)
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Bull, Caroline J.MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom; Bristol Renal, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
(författare)
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Dahm, Christina C.Department of Public Health, Aarhus University, Aarhus, Denmark
(författare)
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Gicquiau, AudreyNutrition and Metabolism Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
(författare)
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Giles, Graham G.Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia
(författare)
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Gunter, Marc J.Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
(författare)
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Haller, ToomasInstitute of Genomics, University of Tartu, Tartu, Estonia
(författare)
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Langhammer, ArnulfHUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway; Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
(författare)
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Larose, Tricia L.Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France; HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway; Department of Community Medicine and Global Health, Institute of Health and Society, University of Oslo, Oslo, Norway
(författare)
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Ljungberg, Börje,Professor,1949-Umeå universitet,Urologi och andrologi(Swepub:umu)bolj0001
(författare)
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Metspalu, AndresInstitute of Genomics, University of Tartu, Tartu, Estonia
(författare)
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Milne, Roger L.Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia
(författare)
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Muller, David C.Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
(författare)
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Nøst, Therese H.Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
(författare)
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Sørgjerd, Elin PettersenHUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway
(författare)
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Prehn, CorneliaMetabolomics and Proteomics Core (MPC), Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
(författare)
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Riboli, ElioDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
(författare)
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Rinaldi, SabinaNutrition and Metabolism Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
(författare)
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Rothwell, Joseph A.Université Paris-Saclay, UVSQ, Inserm, Gustave Roussy, Équipe “Exposome et Hérédité”, CESP UMR1018, Inserm, Villejuif, France
(författare)
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Scalbert, AugustinNutrition and Metabolism Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
(författare)
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Schmidt, Julie A.Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
(författare)
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Severi, GianlucaUniversité Paris-Saclay, UVSQ, Inserm, Gustave Roussy, Équipe “Exposome et Hérédité”, CESP UMR1018, Inserm, Villejuif, France; Department of Statistics, Computer Science and Applications (DISIA), University of Florence, Florence, Italy
(författare)
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Sieri, SabinaEpidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy
(författare)
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Vermeulen, RoelInstitute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, Netherlands
(författare)
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Vincent, Emma E.MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom; Bristol Renal, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
(författare)
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Waldenberger, MelanieResearch Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
(författare)
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Timpson, Nicholas J.MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
(författare)
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Johansson, MattiasGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
(författare)
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Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, FranceMRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:PLoS Medicine: Public Library of Science (PLOS)18:91549-12771549-1676
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- Av författaren/redakt...
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Guida, Florence
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Tan, Vanessa Y.
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Corbin, Laura J.
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Smith-Byrne, Kar ...
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Alcala, Karine
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Langenberg, Clau ...
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visa fler...
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Stewart, Isobel ...
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Butterworth, Ada ...
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Surendran, Prave ...
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Achaintre, David
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Adamski, Jerzy
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Exezarreta, Pila ...
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Bergmann, Manuel ...
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Bull, Caroline J ...
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Dahm, Christina ...
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Gicquiau, Audrey
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Giles, Graham G.
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Gunter, Marc J.
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Haller, Toomas
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Langhammer, Arnu ...
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Larose, Tricia L ...
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Ljungberg, Börje ...
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Metspalu, Andres
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Milne, Roger L.
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Muller, David C.
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Nøst, Therese H.
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Sørgjerd, Elin P ...
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Prehn, Cornelia
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Riboli, Elio
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Rinaldi, Sabina
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Rothwell, Joseph ...
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Scalbert, August ...
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Schmidt, Julie A ...
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Severi, Gianluca
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Sieri, Sabina
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Vermeulen, Roel
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Vincent, Emma E.
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Waldenberger, Me ...
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Timpson, Nichola ...
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Johansson, Matti ...
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