Circulating Isovalerylcarnitine and Lung Cancer Risk: evidence from Mendelian Randomization and Prediagnostic Blood Measurements

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Circulating Isovalerylcarnitine and Lung Cancer Risk : evidence from Mendelian Randomization and Prediagnostic Blood Measurements

Smith-Byrne, Karl (författare): Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France

Cerani, Agustin (författare): 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

Guida, Florence (författare): Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France

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Zhou, Sirui (författare): 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

Agudo, Antonio (författare): Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Institut Català d'Oncologia, Spain

Aleksandrova, Krasimira (författare): 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

Barricarte, Aurelio (författare): Navarra Institute for Health Research (IdiSNA) Pamplona, Spain; CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain

Barranco, Miguel Rodríguez (författare): 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

Bochers, Christoph H. (författare): 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

Gram, Inger Torhild (författare): Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, Arctic University of Norway, Norway

Han, Jun (författare): University of Victoria-Genome British Columbia Proteomics Centre, Victoria, BC, Canada/Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada

Amos, Christopher I. (författare): Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, TX, Houston, United States

Hung, Rayjean J. (författare): Prosserman Centre for Health Research, Mount Sinai Hospital, Toronto, Canada

Grankvist, Kjell (författare): Umeå universitet,Klinisk kemi

Nøst, Therese Haugdhal (författare): Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, Arctic University of Norway, Norway

Imaz, Liher (författare): Ministry of Health of the Basque Government, Public Health Division of Gipuzkoa, Donostia-San Sebastian, Spain; Biodonostia Health Research Institute, Donostia-San Sebastian, Spain

Chirlaque-López, María Dolores (författare): CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain

Johansson, Mikael (författare): Umeå universitet,Onkologi

Kaaks, Rudolf (författare): 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

Kühn, Tilman (författare): German Cancer Research Center (DKFZ), Department of Cancer Epidemiology, Heidelberg, Germany

Martin, Richard M. (författare): Clinical Epidemiology & Public Health, University of Bristol, Bristol, United Kingdom

McKay, James D. (författare): Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France

Pala, Valeria (författare): Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Robbins, Hilary A. (författare): Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France

Sandanger, Torkjel M. (författare): Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, Arctic University of Norway, Norway

Schibli, David (författare): University of Victoria-Genome British Columbia Proteomics Centre, Victoria, BC, Canada/Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada

Schulze, Matthias B. (författare): 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

Travis, Ruth C. (författare): Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom

Vineis, Paolo (författare): Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom

Weiderpass, Elisabete (författare): Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France

Brennan, Paul (författare): Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France

Johansson, Mattias (författare): Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France

Richards, J Brent (författare): 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
Engelska.
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 31:10, s. 1966-1974

Relaterad länk:: https://doi.org/10.1...; visa fler...; https://umu.diva-por... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; visa färre...

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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.

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Cancer Epidemiology, Biomarkers and Prevention (Sök värdpublikationen i LIBRIS)

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

Artiklar i publikationen: Cancer Epidemiol ...

Av lärosätet: Umeå universitet

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Circulating Isovalerylcarnitine and Lung Cancer Risk : evidence from Mendelian Randomization and Prediagnostic Blood Measurements

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