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

Aged Biomarkers, Tumor / blood Case-Control Studies Cholesterol / blood Genome-Wide Association Study Humans Male Mendelian Randomization Analysis Metabolome Middle Aged Phospholipids / blood Prostate-Specific Antigen / blood Prostatic Neoplasms / blood Triglycerides / blood United Kingdom

Journal

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608

Informations de publication

Date de publication:
01 2019
Historique:
received: 26 01 2018
revised: 25 03 2018
accepted: 15 10 2018
pubmed: 26 10 2018
medline: 12 2 2020
entrez: 25 10 2018
Statut: ppublish

Résumé

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). 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. Thirty-five metabolites were strongly associated with prostate cancer ( 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. The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

Sections du résumé

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 (
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.

Identifiants

DOI: 10.1158/1055-9965.EPI-18-0079 PMID: 30352818 PMC: PMC6746173
pubmed: 30352818
pii: 1055-9965.EPI-18-0079
doi: 10.1158/1055-9965.EPI-18-0079
pmc: PMC6746173
mid: NIHMS1048687
doi:

Substances chimiques

Biomarkers, Tumor 0
Phospholipids 0
Triglycerides 0
Cholesterol 97C5T2UQ7J
Prostate-Specific Antigen EC 3.4.21.77

Types de publication

Journal Article Multicenter Study Observational Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

208-216

Subventions

Organisme : Cancer Research UK
ID : A10118
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C11043/A4286
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A16491
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : UG1 CA189974
Pays : United States
Organisme : Cancer Research UK
ID : C5047/A3354
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N003284/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A10692
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A19169
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 14136
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A16563
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C5047/A17528
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A7357
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C8221/A19170
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U10 CA037429
Pays : United States
Organisme : Cancer Research UK
ID : C5047/A7357
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12013/2
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U01 CA182883
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00011/5
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A3354
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C16913/A6135
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C1287/A16563
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C18281/A8145
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U01 CA188392
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12013/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C5047/A10692
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 108902/15/Z
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C18281/A11326
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : HHSN268201200008C
Pays : United States
Organisme : Cancer Research UK
ID : C18281/A19169
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U19 CA148537
Pays : United States
Organisme : Cancer Research UK
ID : A11326
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C570/A16491
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M012190/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A6135
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A17528
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1000143
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : HHSN268201200008I
Pays : United States
Organisme : Cancer Research UK
ID : C1287/A10118
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : UM1 CA182883
Pays : United States

Informations de copyright

©2018 American Association for Cancer Research.

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Auteurs

Charleen D Adams (CD)

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom. chaadams@coh.org.
University of Bristol, Bristol, United Kingdom.

Rebecca Richmond (R)

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.
University of Bristol, Bristol, United Kingdom.

Diana L Santos Ferreira (DLS)

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.
University of Bristol, Bristol, United Kingdom.

Wes Spiller (W)

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.
University of Bristol, Bristol, United Kingdom.

Vanessa Tan (V)

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.
University of Bristol, Bristol, United Kingdom.

Jie Zheng (J)

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.
University of Bristol, Bristol, United Kingdom.

Peter Würtz (P)

Research Programs Unit, Diabetes and Obesity, University of Helsinki and Nightingale Health Ltd., Helsinki, Finland.

Jenny Donovan (J)

University of Bristol, Bristol, United Kingdom.

Freddie Hamdy (F)

Nuffield Department of Surgical Sciences, University of Oxford and Faculty of Medical Science, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.

David Neal (D)

Nuffield Department of Surgical Sciences, University of Oxford and Faculty of Medical Science, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.

J Athene Lane (JA)

University of Bristol, Bristol, United Kingdom.
Bristol National Institute of Health Research Biomedical Research Centre, Bristol, United Kingdom.

George Davey Smith (GD)

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.
University of Bristol, Bristol, United Kingdom.
Bristol National Institute of Health Research Biomedical Research Centre, Bristol, United Kingdom.

Caroline Relton (C)

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.
University of Bristol, Bristol, United Kingdom.
Bristol National Institute of Health Research Biomedical Research Centre, Bristol, United Kingdom.

Rosalind A Eeles (RA)

The Institute of Cancer Research, London, United Kingdom.
Royal Marsden NHS Foundation Trust, London, United Kingdom.

Christopher A Haiman (CA)

Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.

ZSofia Kote-Jarai (Z)

The Institute of Cancer Research, London, United Kingdom.

Fredrick R Schumacher (FR)

Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio.
Seidman Cancer Center, University Hospitals, Cleveland, Ohio.

Ali Amin Al Olama (AAA)

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
University of Cambridge, Department of Clinical Neurosciences, Cambridge, United Kingdom.

Sara Benlloch (S)

The Institute of Cancer Research, London, United Kingdom.
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.

Kenneth Muir (K)

Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, United Kingdom.
Warwick Medical School, University of Warwick, Coventry, United Kingdom.

Sonja I Berndt (SI)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.

David V Conti (DV)

Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.

Fredrik Wiklund (F)

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.

Stephen J Chanock (SJ)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.

Susan Gapstur (S)

Epidemiology Research Program, American Cancer Society, Atlanta, Georgia.

Victoria L Stevens (VL)

Epidemiology Research Program, American Cancer Society, Atlanta, Georgia.

Catherine M Tangen (CM)

SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Jyotsna Batra (J)

Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, Queensland, Australia.
Translational Research Institute, Brisbane, Queensland, Australia.

Judith A Clements (JA)

Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, Queensland, Australia.
Translational Research Institute, Brisbane, Queensland, Australia.

Henrik Gronberg (H)

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.

Nora Pashayan (N)

University College London, Department of Applied Health Research, London, United Kingdom.
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Laboratory, Cambridge, United Kingdom.

Johanna Schleutker (J)

Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Turku, Finland.
Tyks Microbiology and Genetics, Department of Medical Genetics, Turku University Hospital, Turku, Finland.

Demetrius Albanes (D)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.

Alicja Wolk (A)

Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Catharine M L West (CML)

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.

Lorelei A Mucci (LA)

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Géraldine Cancel-Tassin (G)

CeRePP, Tenon Hospital, Paris, France.
UPMC Sorbonne Universités, GRC N°5 ONCOTYPE-URO, Tenon Hospital, Paris, France.

Stella Koutros (S)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.

Karina Dalsgaard Sorensen (KD)

Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Lovise Maehle (L)

Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.

Ruth C Travis (RC)

Cancer Epidemiology Unit, Nuffield Department of Population Health University of Oxford, Oxford, United Kingdom.

Robert J Hamilton (RJ)

Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.

Sue Ann Ingles (SA)

Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.

Barry S Rosenstein (BS)

Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

Yong-Jie Lu (YJ)

Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, London, United Kingdom.

Graham G Giles (GG)

Cancer Epidemiology & Intelligence Division, The Cancer Council Victoria, Melbourne, Victoria, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.

Adam S Kibel (AS)

Division of Urologic Surgery, Brigham and Women's Hospital, Boston, Massachusetts.

Ana Vega (A)

Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica, CIBERER, IDIS, Santiago de Compostela, Spain.

Manolis Kogevinas (M)

Centre for Research in Environmental Epidemiology (CREAL), Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain.
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
IMIM (Hospital del Mar Research Institute), Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.

Kathryn L Penney (KL)

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts.

Jong Y Park (JY)

Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida.

Janet L Stanford (JL)

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.

Cezary Cybulski (C)

International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

Børge G Nordestgaard (BG)

Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.

Hermann Brenner (H)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.

Christiane Maier (C)

Institute for Human Genetics, University Hospital Ulm, Ulm, Germany.

Jeri Kim (J)

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Esther M John (EM)

Cancer Prevention Institute of California, Fremont, California.
Department of Health Research & Policy (Epidemiology) and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California.

Manuel R Teixeira (MR)

Department of Genetics, Portuguese Oncology Institute of Porto, Porto, Portugal.
Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal.

Susan L Neuhausen (SL)

Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, California.

Kim De Ruyck (K)

Ghent University, Faculty of Medicine and Health Sciences, Basic Medical Sciences, Gent, Belgium.

Azad Razack (A)

Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Lisa F Newcomb (LF)

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Department of Urology, University of Washington, Seattle, Washington.

Davor Lessel (D)

Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Radka P Kaneva (RP)

Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University, Sofia, Bulgaria.

Nawaid Usmani (N)

Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.

Frank Claessens (F)

Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.

Paul A Townsend (PA)

Institute of Cancer Sciences, Manchester Cancer Research Centre, University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Manchester, United Kingdom.

Manuela Gago Dominguez (MG)

Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, Servicio Galego de Saúde, SERGAS, Santiago De Compostela, Spain.
University of California San Diego, Moores Cancer Center, La Jolla, California.

Monique J Roobol (MJ)

Department of Urology, Erasmus University Medical Center, Rotterdam, the Netherlands.

Florence Menegaux (F)

Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France.

Kay-Tee Khaw (KT)

Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom.

Lisa A Cannon-Albright (LA)

Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah.
George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah.

Hardev Pandha (H)

The University of Surrey, Guildford, Surrey, United Kingdom.

Stephen N Thibodeau (SN)

Richard M Martin (RM)

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.
University of Bristol, Bristol, United Kingdom.
Bristol National Institute of Health Research Biomedical Research Centre, Bristol, United Kingdom.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Circulating Metabolic Biomarkers of...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Circulating Metabolic Biomarkers of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › Circulating Metabolic Biomarkers of...
questionsmedicales.fr › Lipides › Lipides membranaires › Stérols › Cholestérol › Circulating Metabolic Biomarkers of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Circulating Metabolic Biomarkers of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Circulating Metabolic Biomarkers of...
questionsmedicales.fr › Techniques d'investigation › Analyse de randomisation mendélienne › Circulating Metabolic Biomarkers of...
questionsmedicales.fr › Métabolisme › Métabolome › Circulating Metabolic Biomarkers of...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Circulating Metabolic Biomarkers of...
questionsmedicales.fr › Lipides › Lipides membranaires › Phospholipides › Circulating Metabolic Biomarkers of...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Antigène spécifique de la prostate › Circulating Metabolic Biomarkers of...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Circulating Metabolic Biomarkers of...
questionsmedicales.fr › Lipides › Glycérides › Triglycéride › Circulating Metabolic Biomarkers of...
questionsmedicales.fr › Régions géographiques › Europe › Royaume-Uni › Circulating Metabolic Biomarkers of...