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Sökning: onr:"swepub:oai:DiVA.org:umu-188614" > The blood metabolom...

The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium

Guida, Florence (författare)
Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
Tan, Vanessa Y. (författare)
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
Corbin, Laura J. (författare)
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
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Smith-Byrne, Karl (författare)
Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
Alcala, Karine (författare)
Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
Langenberg, Claudia (författare)
MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom
Stewart, Isobel D. (författare)
MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom
Butterworth, Adam S. (författare)
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
Surendran, Praveen (författare)
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; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
Achaintre, David (författare)
Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
Adamski, Jerzy (författare)
Institute 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
Exezarreta, Pilar Amiano (författare)
Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
Bergmann, Manuela M. (författare)
German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
Bull, Caroline J. (författare)
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
Dahm, Christina C. (författare)
Department of Public Health, Aarhus University, Aarhus, Denmark
Gicquiau, Audrey (författare)
Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
Giles, Graham G. (författare)
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
Gunter, Marc J. (författare)
Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
Haller, Toomas (författare)
Institute of Genomics, University of Tartu, Tartu, Estonia
Langhammer, Arnulf (författare)
HUNT 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
Larose, Tricia L. (författare)
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
Ljungberg, Börje, Professor, 1949- (författare)
Umeå universitet,Urologi och andrologi
Metspalu, Andres (författare)
Institute of Genomics, University of Tartu, Tartu, Estonia
Milne, Roger L. (författare)
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
Muller, David C. (författare)
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
Nøst, Therese H. (författare)
Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
Sørgjerd, Elin Pettersen (författare)
HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway
Prehn, Cornelia (författare)
Metabolomics and Proteomics Core (MPC), Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
Riboli, Elio (författare)
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
Rinaldi, Sabina (författare)
Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
Rothwell, Joseph A. (författare)
Université Paris-Saclay, UVSQ, Inserm, Gustave Roussy, Équipe “Exposome et Hérédité”, CESP UMR1018, Inserm, Villejuif, France
Scalbert, Augustin (författare)
Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
Schmidt, Julie A. (författare)
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
Severi, Gianluca (författare)
Université 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
Sieri, Sabina (författare)
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy
Vermeulen, Roel (författare)
Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, Netherlands
Vincent, Emma E. (författare)
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
Waldenberger, Melanie (författare)
Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
Timpson, Nicholas J. (författare)
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
Johansson, Mattias (författare)
Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
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 (creator_code:org_t)
2021-09-20
2021
Engelska.
Ingår i: PLoS Medicine. - : Public Library of Science (PLOS). - 1549-1277 .- 1549-1676. ; 18:9
Relaterad länk:
https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
https://journals.plo...
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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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

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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