Karina Dalsgaard Sørensen

Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Charleen D Adams, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
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  • Rebecca Richmond, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
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  • Diana L Santos Ferreira, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
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  • Wes Spiller, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
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  • Vanessa Tan, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
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  • Jie Zheng, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
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  • Peter Würtz, Research Programs Unit, Diabetes and Obesity, University of Helsinki and Nightingale Health Ltd., Helsinki, Finland.
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  • Jenny Donovan, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
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  • Freddie Hamdy, Nuffield Department of Surgical Sciences, University of Oxford and Faculty of Medical Science, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
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  • David Neal, Nuffield Department of Surgical Sciences, University of Oxford and Faculty of Medical Science, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
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  • J Athene Lane, Bristol National Institute of Health Research Biomedical Research Centre, Bristol, United Kingdom.
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  • George Davey Smith, Bristol National Institute of Health Research Biomedical Research Centre, Bristol, United Kingdom.
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  • Caroline Relton, Bristol National Institute of Health Research Biomedical Research Centre, Bristol, United Kingdom.
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  • Rosalind A Eeles, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom.
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  • Christopher A Haiman, Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
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  • ZSofia Kote-Jarai, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
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  • Fredrick R Schumacher, Seidman Cancer Center, University Hospitals, Cleveland, Ohio.
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  • Ali Amin Al Olama, Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Addenbrookes Hospital, Neurology Unit, Cambridge, United Kingdom
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  • Sara Benlloch, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom.
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  • Kenneth Muir, Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom.
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  • Sonja I Berndt, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
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  • David V Conti, Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
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  • Fredrik Wiklund, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
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  • Stephen J Chanock, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
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  • Susan Gapstur, Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA.
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  • Victoria L Stevens, Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA.
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  • Catherine M Tangen, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
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  • Jyotsna Batra, University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
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  • Judith A Clements, University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
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  • Henrik Gronberg, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
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  • Nora Pashayan, Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Laboratory, Cambridge, United Kingdom.
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  • Johanna Schleutker, Tyks Microbiology and Genetics, Department of Medical Genetics, Turku University Hospital, 20521, Turku, Finland.
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  • Demetrius Albanes, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
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  • Alicja Wolk, Department of Food Science, BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden; Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
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  • Catharine M L West, Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research, Manchester NIHR Biomedical Research Centre, The Christie Hospital NHS Foundation Trust, Manchester, United Kingdom.
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  • Lorelei A Mucci, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
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  • Géraldine Cancel-Tassin, UPMC Sorbonne Universités, GRC N°5 ONCOTYPE-URO, Tenon Hospital, Paris, France.
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  • Stella Koutros, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
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  • Karina Dalsgaard Sorensen
  • Lovise Maehle, Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
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  • Ruth C Travis, Cancer Epidemiology Unit, Nuffield Department of Population Health University of Oxford, United Kingdom.
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  • Robert J Hamilton, Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, ON, M5G 2M9, Canada.
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  • Sue Ann Ingles, Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
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  • Barry S Rosenstein, Icahn Institute for Genomics and Multiscale Biology and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
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  • Yong-Jie Lu, Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, London, United Kingdom.
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  • Graham G Giles, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia.
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  • Adam S Kibel, Division of Urologic Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
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  • Ana Vega, Fundacion Publica Galega de Medicina Xenomica-SERGAS, Grupo de Medicina Xenomica-USC, IDIS, CIBERER, Santiago de Compostela, Spain.
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  • Manolis Kogevinas, Departament de Ciències Experimentals i de la Salut (UPF), Universitat Pompeu Fabra, Barcelona, Spain.
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  • Kathryn L Penney, 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
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  • The PRACTICAL Consortium
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  • Richard M Martin, University of Bristol, United Kingdom
  • Børge G. Nordestgaard, University of Copenhagen, Gentofte Hospital

BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).

METHODS: The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.

RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.

CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.

IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

Original languageEnglish
JournalCancer Epidemiology, Biomarkers & Prevention
Volume28
Issue1
Pages (from-to)208-216
Number of pages9
ISSN1055-9965
DOIs
Publication statusPublished - Jan 2019

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