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Circulating Isovale...
Circulating Isovalerylcarnitine and Lung Cancer Risk : evidence from Mendelian Randomization and Prediagnostic Blood Measurements
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- Smith-Byrne, Karl (author)
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France
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- Cerani, Agustin (author)
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Canada/Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada
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- Guida, Florence (author)
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France
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- Zhou, Sirui (author)
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Canada/Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada
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- Agudo, Antonio (author)
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Institut Català d'Oncologia, Spain
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- Aleksandrova, Krasimira (author)
- Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany; University of Potsdam, Institute of Nutritional Science, Potsdam, Germany
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- Barricarte, Aurelio (author)
- Navarra Institute for Health Research (IdiSNA) Pamplona, Spain; CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain
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- Barranco, Miguel Rodríguez (author)
- CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain
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- Bochers, Christoph H. (author)
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Canada/Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; University of Victoria-Genome British Columbia Proteomics Centre, Victoria, BC, Canada/Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
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- Gram, Inger Torhild (author)
- Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, Arctic University of Norway, Norway
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- Han, Jun (author)
- University of Victoria-Genome British Columbia Proteomics Centre, Victoria, BC, Canada/Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
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- Amos, Christopher I. (author)
- Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, TX, Houston, United States
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- Hung, Rayjean J. (author)
- Prosserman Centre for Health Research, Mount Sinai Hospital, Toronto, Canada
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- Grankvist, Kjell (author)
- Umeå universitet,Klinisk kemi
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- Nøst, Therese Haugdhal (author)
- Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, Arctic University of Norway, Norway
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- Imaz, Liher (author)
- Ministry of Health of the Basque Government, Public Health Division of Gipuzkoa, Donostia-San Sebastian, Spain; Biodonostia Health Research Institute, Donostia-San Sebastian, Spain
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- Chirlaque-López, María Dolores (author)
- CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain
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- Johansson, Mikael (author)
- Umeå universitet,Onkologi
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- Kaaks, Rudolf (author)
- German Cancer Research Center (DKFZ), Department of Cancer Epidemiology, Heidelberg, Germany; Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Germany
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- Kühn, Tilman (author)
- German Cancer Research Center (DKFZ), Department of Cancer Epidemiology, Heidelberg, Germany
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- Martin, Richard M. (author)
- Clinical Epidemiology & Public Health, University of Bristol, Bristol, United Kingdom
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- McKay, James D. (author)
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France
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- Pala, Valeria (author)
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
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- Robbins, Hilary A. (author)
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France
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- Sandanger, Torkjel M. (author)
- Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, Arctic University of Norway, Norway
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- Schibli, David (author)
- University of Victoria-Genome British Columbia Proteomics Centre, Victoria, BC, Canada/Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
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- Schulze, Matthias B. (author)
- Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany; University of Potsdam, Institute of Nutritional Science, Potsdam, Germany
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- Travis, Ruth C. (author)
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
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- Vineis, Paolo (author)
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
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- Weiderpass, Elisabete (author)
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France
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- Brennan, Paul (author)
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France
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- Johansson, Mattias (author)
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France
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- Richards, J Brent (author)
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Canada/Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; Division of Endocrinology, Department of Medicine & Department of Human Genetics, McGill University, QC, Montreal, Canada; Department of Twin Research and Genetic Epidemiology, King's College London, Strand, London, United Kingdom
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(creator_code:org_t)
- 2022
- 2022
- English.
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 31:10, s. 1966-1974
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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Abstract
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- BACKGROUND: Tobacco exposure causes 8 of 10 lung cancers, and identifying additional risk factors is challenging due to confounding introduced by smoking in traditional observational studies.MATERIALS AND METHODS: We used Mendelian randomization (MR) to screen 207 metabolites for their role in lung cancer predisposition using independent genome-wide association studies (GWAS) of blood metabolite levels (n = 7,824) and lung cancer risk (n = 29,266 cases/56,450 controls). A nested case-control study (656 cases and 1,296 matched controls) was subsequently performed using prediagnostic blood samples to validate MR association with lung cancer incidence data from population-based cohorts (EPIC and NSHDS).RESULTS: An MR-based scan of 207 circulating metabolites for lung cancer risk identified that blood isovalerylcarnitine (IVC) was associated with a decreased odds of lung cancer after accounting for multiple testing (log10-OR = 0.43; 95% CI, 0.29-0.63). Molar measurement of IVC in prediagnostic blood found similar results (log10-OR = 0.39; 95% CI, 0.21-0.72). Results were consistent across lung cancer subtypes.CONCLUSIONS: Independent lines of evidence support an inverse association of elevated circulating IVC with lung cancer risk through a novel methodologic approach that integrates genetic and traditional epidemiology to efficiently identify novel cancer biomarkers.IMPACT: Our results find compelling evidence in favor of a protective role for a circulating metabolite, IVC, in lung cancer etiology. From the treatment of a Mendelian disease, isovaleric acidemia, we know that circulating IVC is modifiable through a restricted protein diet or glycine and L-carnatine supplementation. IVC may represent a modifiable and inversely associated biomarker for lung cancer.
Subject headings
- 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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- ref (subject category)
- art (subject category)
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- By the author/editor
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Smith-Byrne, Kar ...
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Cerani, Agustin
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Guida, Florence
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Zhou, Sirui
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Agudo, Antonio
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Aleksandrova, Kr ...
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Barricarte, Aure ...
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Barranco, Miguel ...
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Bochers, Christo ...
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Gram, Inger Torh ...
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Han, Jun
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Amos, Christophe ...
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Hung, Rayjean J.
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Grankvist, Kjell
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Nøst, Therese Ha ...
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Imaz, Liher
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Chirlaque-López, ...
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Johansson, Mikae ...
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Kaaks, Rudolf
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Kühn, Tilman
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Martin, Richard ...
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McKay, James D.
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Pala, Valeria
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Robbins, Hilary ...
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Sandanger, Torkj ...
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Schibli, David
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Schulze, Matthia ...
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Travis, Ruth C.
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Vineis, Paolo
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Weiderpass, Elis ...
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Brennan, Paul
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Johansson, Matti ...
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Richards, J Bren ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Cancer Epidemiol ...
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Umeå University