The effects of height and BMI on prostate cancer incidence and mortality: a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium
Identifieur interne : 000B26 ( Pmc/Curation ); précédent : 000B25; suivant : 000B27The effects of height and BMI on prostate cancer incidence and mortality: a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium
Auteurs : Neil M. Davies [Royaume-Uni] ; Tom R. Gaunt [Royaume-Uni] ; Sarah J. Lewis [Royaume-Uni] ; Jeff Holly ; Jenny L. Donovan [Royaume-Uni] ; Freddie C. Hamdy [Royaume-Uni] ; John P. Kemp [Royaume-Uni] ; Rosalind Eeles ; Doug Easton [Royaume-Uni] ; Zsofia Kote-Jarai ; Ali Amin Al Olama [Royaume-Uni] ; Sara Benlloch [Royaume-Uni] ; Kenneth Muir [Royaume-Uni] ; Graham G. Giles [Australie] ; Fredrik Wiklund [Suède] ; Henrik Gronberg [Suède] ; Christopher A. Haiman [États-Unis] ; Johanna Schleutker [Finlande] ; B Rge G. Nordestgaard [Danemark] ; Ruth C. Travis [Royaume-Uni] ; David Neal [Royaume-Uni] ; Nora Pashayan [Royaume-Uni] ; Kay-Tee Khaw [Royaume-Uni] ; Janet L. Stanford [États-Unis] ; William J. Blot [États-Unis] ; Stephen Thibodeau [États-Unis] ; Christiane Maier [Allemagne] ; Adam S. Kibel [États-Unis] ; Cezary Cybulski [Pologne] ; Lisa Cannon-Albright [États-Unis] ; Hermann Brenner [Allemagne] ; Jong Park [États-Unis] ; Radka Kaneva [Bulgarie] ; Jyotsna Batra ; Manuel R. Teixeira [Portugal] ; Hardev Pandha ; Mark Lathrop [France, Canada] ; George Davey Smith [Royaume-Uni] ; Richard M. Martin [Royaume-Uni]Source :
- Cancer Causes & Control [ 0957-5243 ] ; 2015.
Abstract
Epidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality.
We conducted a case–control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man’s number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies.
The genetic risk scores explained 6.31 and 1.46 % of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95 % CI 0.96, 1.00;
We found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication.
The online version of this article (doi:10.1007/s10552-015-0654-9) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1007/s10552-015-0654-9
PubMed: 26387087
PubMed Central: 4596899
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Jeff Holly<affiliation><nlm:aff id="Aff3">School of Clinical Sciences, University of Bristol, Bristol, BS10 5NB UK</nlm:aff><wicri:noCountry code="subfield">BS10 5NB UK</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff5">University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD Australia</nlm:aff><wicri:noCountry code="subfield">QLD Australia</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff6">The Institute of Cancer Research, London, SM2 5NG UK</nlm:aff><wicri:noCountry code="subfield">SM2 5NG UK</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff7">The Royal Marsden NHS Foundation Trust, London, SW3 6JJ UK</nlm:aff><wicri:noCountry code="subfield">SW3 6JJ UK</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff7">The Royal Marsden NHS Foundation Trust, London, SW3 6JJ UK</nlm:aff><wicri:noCountry code="subfield">SW3 6JJ UK</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff6">The Institute of Cancer Research, London, SM2 5NG UK</nlm:aff><wicri:noCountry code="subfield">SM2 5NG UK</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff10">Cancer Epidemiology Centre, The Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="Aff11">Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC Australia</nlm:aff><orgName type="university">Université de Melbourne</orgName><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation><nlm:aff id="Aff37">Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD Australia</nlm:aff><wicri:noCountry code="subfield">QLD Australia</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff40">The University of Surrey, Guildford, Surrey GU2 7XH UK</nlm:aff><wicri:noCountry code="subfield">Surrey GU2 7XH UK</wicri:noCountry></affiliation>Le document en format XML
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Davies</name><affiliation wicri:level="1"><nlm:aff id="Aff1">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, University of Bristol, Bristol</wicri:regionArea></affiliation></author><author><name sortKey="Gaunt, Tom R" sort="Gaunt, Tom R" uniqKey="Gaunt T" first="Tom R." last="Gaunt">Tom R. Gaunt</name><affiliation wicri:level="1"><nlm:aff id="Aff1">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, University of Bristol, Bristol</wicri:regionArea></affiliation></author><author><name sortKey="Lewis, Sarah J" sort="Lewis, Sarah J" uniqKey="Lewis S" first="Sarah J." last="Lewis">Sarah J. Lewis</name><affiliation wicri:level="1"><nlm:aff id="Aff1">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, University of Bristol, Bristol</wicri:regionArea></affiliation></author><author><name sortKey="Holly, Jeff" sort="Holly, Jeff" uniqKey="Holly J" first="Jeff" last="Holly">Jeff Holly</name><affiliation><nlm:aff id="Aff3">School of Clinical Sciences, University of Bristol, Bristol, BS10 5NB UK</nlm:aff><wicri:noCountry code="subfield">BS10 5NB UK</wicri:noCountry></affiliation></author><author><name sortKey="Donovan, Jenny L" sort="Donovan, Jenny L" uniqKey="Donovan J" first="Jenny L." last="Donovan">Jenny L. Donovan</name><affiliation wicri:level="1"><nlm:aff id="Aff1">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea></affiliation></author><author><name sortKey="Hamdy, Freddie C" sort="Hamdy, Freddie C" uniqKey="Hamdy F" first="Freddie C." last="Hamdy">Freddie C. Hamdy</name><affiliation wicri:level="1"><nlm:aff id="Aff4">Nuffield Department of Surgery, University of Oxford, Oxford, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Nuffield Department of Surgery, University of Oxford, Oxford</wicri:regionArea></affiliation></author><author><name sortKey="Kemp, John P" sort="Kemp, John P" uniqKey="Kemp J" first="John P." last="Kemp">John P. Kemp</name><affiliation wicri:level="1"><nlm:aff id="Aff2">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, University of Bristol, Bristol</wicri:regionArea></affiliation><affiliation><nlm:aff id="Aff5">University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD Australia</nlm:aff><wicri:noCountry code="subfield">QLD Australia</wicri:noCountry></affiliation></author><author><name sortKey="Eeles, Rosalind" sort="Eeles, Rosalind" uniqKey="Eeles R" first="Rosalind" last="Eeles">Rosalind Eeles</name><affiliation><nlm:aff id="Aff6">The Institute of Cancer Research, London, SM2 5NG UK</nlm:aff><wicri:noCountry code="subfield">SM2 5NG UK</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff7">The Royal Marsden NHS Foundation Trust, London, SW3 6JJ UK</nlm:aff><wicri:noCountry code="subfield">SW3 6JJ UK</wicri:noCountry></affiliation></author><author><name sortKey="Easton, Doug" sort="Easton, Doug" uniqKey="Easton D" first="Doug" last="Easton">Doug Easton</name><affiliation wicri:level="1"><nlm:aff id="Aff8">Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Kote Jarai, Zsofia" sort="Kote Jarai, Zsofia" uniqKey="Kote Jarai Z" first="Zsofia" last="Kote-Jarai">Zsofia Kote-Jarai</name><affiliation><nlm:aff id="Aff6">The Institute of Cancer Research, London, SM2 5NG UK</nlm:aff><wicri:noCountry code="subfield">SM2 5NG UK</wicri:noCountry></affiliation></author><author><name sortKey="Al Olama, Ali Amin" sort="Al Olama, Ali Amin" uniqKey="Al Olama A" first="Ali Amin" last="Al Olama">Ali Amin Al Olama</name><affiliation wicri:level="1"><nlm:aff id="Aff8">Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Benlloch, Sara" sort="Benlloch, Sara" uniqKey="Benlloch S" first="Sara" last="Benlloch">Sara Benlloch</name><affiliation wicri:level="1"><nlm:aff id="Aff8">Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Muir, Kenneth" sort="Muir, Kenneth" uniqKey="Muir K" first="Kenneth" last="Muir">Kenneth Muir</name><affiliation wicri:level="1"><nlm:aff id="Aff9">Institute of Population Health, University of Manchester, Manchester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Population Health, University of Manchester, Manchester</wicri:regionArea></affiliation></author><author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name><affiliation><nlm:aff id="Aff10">Cancer Epidemiology Centre, The Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="Aff11">Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC Australia</nlm:aff><orgName type="university">Université de Melbourne</orgName><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Wiklund, Fredrik" sort="Wiklund, Fredrik" uniqKey="Wiklund F" first="Fredrik" last="Wiklund">Fredrik Wiklund</name><affiliation wicri:level="1"><nlm:aff id="Aff12">Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm</wicri:regionArea></affiliation></author><author><name sortKey="Gronberg, Henrik" sort="Gronberg, Henrik" uniqKey="Gronberg H" first="Henrik" last="Gronberg">Henrik Gronberg</name><affiliation wicri:level="1"><nlm:aff id="Aff12">Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm</wicri:regionArea></affiliation></author><author><name sortKey="Haiman, Christopher A" sort="Haiman, Christopher A" uniqKey="Haiman C" first="Christopher A." last="Haiman">Christopher A. Haiman</name><affiliation wicri:level="2"><nlm:aff id="Aff13">Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles</wicri:cityArea></affiliation></author><author><name sortKey="Schleutker, Johanna" sort="Schleutker, Johanna" uniqKey="Schleutker J" first="Johanna" last="Schleutker">Johanna Schleutker</name><affiliation wicri:level="1"><nlm:aff id="Aff14">Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Medical Biochemistry and Genetics, University of Turku, Turku</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff15">Institute of Biomedical Technology/BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute of Biomedical Technology/BioMediTech, University of Tampere and FimLab Laboratories, Tampere</wicri:regionArea></affiliation></author><author><name sortKey="Nordestgaard, B Rge G" sort="Nordestgaard, B Rge G" uniqKey="Nordestgaard B" first="B Rge G." last="Nordestgaard">B Rge G. Nordestgaard</name><affiliation wicri:level="1"><nlm:aff id="Aff16">Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, 2730 Herlev</wicri:regionArea></affiliation></author><author><name sortKey="Travis, Ruth C" sort="Travis, Ruth C" uniqKey="Travis R" first="Ruth C." last="Travis">Ruth C. Travis</name><affiliation wicri:level="1"><nlm:aff id="Aff17">Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford</wicri:regionArea></affiliation></author><author><name sortKey="Neal, David" sort="Neal, David" uniqKey="Neal D" first="David" last="Neal">David Neal</name><affiliation wicri:level="1"><nlm:aff id="Aff18">Surgical Oncology (Uro-Oncology: S4), University of Cambridge, Addenbrooke’s Hospital, Hills Road, Box 279, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Surgical Oncology (Uro-Oncology: S4), University of Cambridge, Addenbrooke’s Hospital, Hills Road, Box 279, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff19">Li Ka Shing Centre, Cancer Research UK Cambridge Research Institute, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Li Ka Shing Centre, Cancer Research UK Cambridge Research Institute, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Pashayan, Nora" sort="Pashayan, Nora" uniqKey="Pashayan N" first="Nora" last="Pashayan">Nora Pashayan</name><affiliation wicri:level="1"><nlm:aff id="Aff20">Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Worts Causeway, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Worts Causeway, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="4"><nlm:aff id="Aff41">Department of Applied Health Research, University College London, 1-19 Torrington Place, London, WC1E 7HB UK</nlm:aff><orgName type="university">University College de Londres</orgName><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Khaw, Kay Tee" sort="Khaw, Kay Tee" uniqKey="Khaw K" first="Kay-Tee" last="Khaw">Kay-Tee Khaw</name><affiliation wicri:level="4"><nlm:aff id="Aff21">Cambridge Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0SR UK</nlm:aff><orgName type="university">Université de Cambridge</orgName><country>Royaume-Uni</country><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation></author><author><name sortKey="Stanford, Janet L" sort="Stanford, Janet L" uniqKey="Stanford J" first="Janet L." last="Stanford">Janet L. Stanford</name><affiliation wicri:level="2"><nlm:aff id="Aff22">Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff23">Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Department of Epidemiology, School of Public Health, University of Washington, Seattle</wicri:cityArea></affiliation></author><author><name sortKey="Blot, William J" sort="Blot, William J" uniqKey="Blot W" first="William J." last="Blot">William J. Blot</name><affiliation wicri:level="2"><nlm:aff id="Aff24">International Epidemiology Institute, 1455 Research Blvd., Suite 550, Rockville, MD 20850 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>International Epidemiology Institute, 1455 Research Blvd., Suite 550, Rockville</wicri:cityArea></affiliation></author><author><name sortKey="Thibodeau, Stephen" sort="Thibodeau, Stephen" uniqKey="Thibodeau S" first="Stephen" last="Thibodeau">Stephen Thibodeau</name><affiliation wicri:level="2"><nlm:aff id="Aff25">Mayo Clinic, Rochester, MN USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>Mayo Clinic, Rochester</wicri:cityArea></affiliation></author><author><name sortKey="Maier, Christiane" sort="Maier, Christiane" uniqKey="Maier C" first="Christiane" last="Maier">Christiane Maier</name><affiliation wicri:level="1"><nlm:aff id="Aff26">Department of Urology, University Hospital Ulm, Ulm, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Urology, University Hospital Ulm, Ulm</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff27">Institute of Human Genetics, University Hospital Ulm, Ulm, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Human Genetics, University Hospital Ulm, Ulm</wicri:regionArea></affiliation></author><author><name sortKey="Kibel, Adam S" sort="Kibel, Adam S" uniqKey="Kibel A" first="Adam S." last="Kibel">Adam S. Kibel</name><affiliation wicri:level="2"><nlm:aff id="Aff28">Brigham and Women’s Hospital/Dana-Farber Cancer Institute, 45 Francis Street-ASB II-3, Boston, MA 02115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Brigham and Women’s Hospital/Dana-Farber Cancer Institute, 45 Francis Street-ASB II-3, Boston</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff29">Washington University, St. Louis, Missouri</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Missouri (État)</region></placeName><wicri:cityArea>Washington University, St. Louis</wicri:cityArea></affiliation></author><author><name sortKey="Cybulski, Cezary" sort="Cybulski, Cezary" uniqKey="Cybulski C" first="Cezary" last="Cybulski">Cezary Cybulski</name><affiliation wicri:level="1"><nlm:aff id="Aff30">International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland</nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea>International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin</wicri:regionArea></affiliation></author><author><name sortKey="Cannon Albright, Lisa" sort="Cannon Albright, Lisa" uniqKey="Cannon Albright L" first="Lisa" last="Cannon-Albright">Lisa Cannon-Albright</name><affiliation wicri:level="2"><nlm:aff id="Aff31">Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City</wicri:cityArea></affiliation></author><author><name sortKey="Brenner, Hermann" sort="Brenner, Hermann" uniqKey="Brenner H" first="Hermann" last="Brenner">Hermann Brenner</name><affiliation wicri:level="1"><nlm:aff id="Aff32">Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff33">Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff34">German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea></affiliation></author><author><name sortKey="Park, Jong" sort="Park, Jong" uniqKey="Park J" first="Jong" last="Park">Jong Park</name><affiliation wicri:level="2"><nlm:aff id="Aff35">Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr., Tampa, FL USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr., Tampa</wicri:cityArea></affiliation></author><author><name sortKey="Kaneva, Radka" sort="Kaneva, Radka" uniqKey="Kaneva R" first="Radka" last="Kaneva">Radka Kaneva</name><affiliation wicri:level="1"><nlm:aff id="Aff36">Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University Sofia, 2 Zdrave St, 1431 Sofia, Bulgaria</nlm:aff><country xml:lang="fr">Bulgarie</country><wicri:regionArea>Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University Sofia, 2 Zdrave St, 1431 Sofia</wicri:regionArea></affiliation></author><author><name sortKey="Batra, Jyotsna" sort="Batra, Jyotsna" uniqKey="Batra J" first="Jyotsna" last="Batra">Jyotsna Batra</name><affiliation><nlm:aff id="Aff37">Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD Australia</nlm:aff><wicri:noCountry code="subfield">QLD Australia</wicri:noCountry></affiliation></author><author><name sortKey="Teixeira, Manuel R" sort="Teixeira, Manuel R" uniqKey="Teixeira M" first="Manuel R." last="Teixeira">Manuel R. Teixeira</name><affiliation wicri:level="1"><nlm:aff id="Aff38">Department of Genetics, Portuguese Oncology Institute, Porto, Portugal</nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>Department of Genetics, Portuguese Oncology Institute, Porto</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff39">Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal</nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>Biomedical Sciences Institute (ICBAS), Porto University, Porto</wicri:regionArea></affiliation></author><author><name sortKey="Pandha, Hardev" sort="Pandha, Hardev" uniqKey="Pandha H" first="Hardev" last="Pandha">Hardev Pandha</name><affiliation><nlm:aff id="Aff40">The University of Surrey, Guildford, Surrey GU2 7XH UK</nlm:aff><wicri:noCountry code="subfield">Surrey GU2 7XH UK</wicri:noCountry></affiliation></author><author><name sortKey="Lathrop, Mark" sort="Lathrop, Mark" uniqKey="Lathrop M" first="Mark" last="Lathrop">Mark Lathrop</name><affiliation wicri:level="1"><nlm:aff id="Aff42">Commissariat à l’Energie Atomique, Center National de Génotypage, Evry, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Commissariat à l’Energie Atomique, Center National de Génotypage, Evry</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff43">McGill University-Génome Québec Innovation Centre, Montreal, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>McGill University-Génome Québec Innovation Centre, Montreal</wicri:regionArea></affiliation></author><author><name sortKey="Smith, George Davey" sort="Smith, George Davey" uniqKey="Smith G" first="George Davey" last="Smith">George Davey Smith</name><affiliation wicri:level="1"><nlm:aff id="Aff1">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, University of Bristol, Bristol</wicri:regionArea></affiliation></author><author><name sortKey="Martin, Richard M" sort="Martin, Richard M" uniqKey="Martin R" first="Richard M." last="Martin">Richard M. Martin</name><affiliation wicri:level="1"><nlm:aff id="Aff1">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, University of Bristol, Bristol</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff44">Bristol Nutrition Biomedical Research Unit, National Institute for Health Research, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Bristol Nutrition Biomedical Research Unit, National Institute for Health Research, Bristol</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26387087</idno><idno type="pmc">4596899</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596899</idno><idno type="RBID">PMC:4596899</idno><idno type="doi">10.1007/s10552-015-0654-9</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000B49</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B49</idno><idno type="wicri:Area/Pmc/Curation">000B26</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000B26</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The effects of height and BMI on prostate cancer incidence and mortality: a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium</title><author><name sortKey="Davies, Neil M" sort="Davies, Neil M" uniqKey="Davies N" first="Neil M." last="Davies">Neil M. Davies</name><affiliation wicri:level="1"><nlm:aff id="Aff1">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, University of Bristol, Bristol</wicri:regionArea></affiliation></author><author><name sortKey="Gaunt, Tom R" sort="Gaunt, Tom R" uniqKey="Gaunt T" first="Tom R." last="Gaunt">Tom R. Gaunt</name><affiliation wicri:level="1"><nlm:aff id="Aff1">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, University of Bristol, Bristol</wicri:regionArea></affiliation></author><author><name sortKey="Lewis, Sarah J" sort="Lewis, Sarah J" uniqKey="Lewis S" first="Sarah J." last="Lewis">Sarah J. Lewis</name><affiliation wicri:level="1"><nlm:aff id="Aff1">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, University of Bristol, Bristol</wicri:regionArea></affiliation></author><author><name sortKey="Holly, Jeff" sort="Holly, Jeff" uniqKey="Holly J" first="Jeff" last="Holly">Jeff Holly</name><affiliation><nlm:aff id="Aff3">School of Clinical Sciences, University of Bristol, Bristol, BS10 5NB UK</nlm:aff><wicri:noCountry code="subfield">BS10 5NB UK</wicri:noCountry></affiliation></author><author><name sortKey="Donovan, Jenny L" sort="Donovan, Jenny L" uniqKey="Donovan J" first="Jenny L." last="Donovan">Jenny L. Donovan</name><affiliation wicri:level="1"><nlm:aff id="Aff1">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea></affiliation></author><author><name sortKey="Hamdy, Freddie C" sort="Hamdy, Freddie C" uniqKey="Hamdy F" first="Freddie C." last="Hamdy">Freddie C. Hamdy</name><affiliation wicri:level="1"><nlm:aff id="Aff4">Nuffield Department of Surgery, University of Oxford, Oxford, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Nuffield Department of Surgery, University of Oxford, Oxford</wicri:regionArea></affiliation></author><author><name sortKey="Kemp, John P" sort="Kemp, John P" uniqKey="Kemp J" first="John P." last="Kemp">John P. Kemp</name><affiliation wicri:level="1"><nlm:aff id="Aff2">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, University of Bristol, Bristol</wicri:regionArea></affiliation><affiliation><nlm:aff id="Aff5">University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD Australia</nlm:aff><wicri:noCountry code="subfield">QLD Australia</wicri:noCountry></affiliation></author><author><name sortKey="Eeles, Rosalind" sort="Eeles, Rosalind" uniqKey="Eeles R" first="Rosalind" last="Eeles">Rosalind Eeles</name><affiliation><nlm:aff id="Aff6">The Institute of Cancer Research, London, SM2 5NG UK</nlm:aff><wicri:noCountry code="subfield">SM2 5NG UK</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff7">The Royal Marsden NHS Foundation Trust, London, SW3 6JJ UK</nlm:aff><wicri:noCountry code="subfield">SW3 6JJ UK</wicri:noCountry></affiliation></author><author><name sortKey="Easton, Doug" sort="Easton, Doug" uniqKey="Easton D" first="Doug" last="Easton">Doug Easton</name><affiliation wicri:level="1"><nlm:aff id="Aff8">Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Kote Jarai, Zsofia" sort="Kote Jarai, Zsofia" uniqKey="Kote Jarai Z" first="Zsofia" last="Kote-Jarai">Zsofia Kote-Jarai</name><affiliation><nlm:aff id="Aff6">The Institute of Cancer Research, London, SM2 5NG UK</nlm:aff><wicri:noCountry code="subfield">SM2 5NG UK</wicri:noCountry></affiliation></author><author><name sortKey="Al Olama, Ali Amin" sort="Al Olama, Ali Amin" uniqKey="Al Olama A" first="Ali Amin" last="Al Olama">Ali Amin Al Olama</name><affiliation wicri:level="1"><nlm:aff id="Aff8">Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Benlloch, Sara" sort="Benlloch, Sara" uniqKey="Benlloch S" first="Sara" last="Benlloch">Sara Benlloch</name><affiliation wicri:level="1"><nlm:aff id="Aff8">Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Muir, Kenneth" sort="Muir, Kenneth" uniqKey="Muir K" first="Kenneth" last="Muir">Kenneth Muir</name><affiliation wicri:level="1"><nlm:aff id="Aff9">Institute of Population Health, University of Manchester, Manchester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Population Health, University of Manchester, Manchester</wicri:regionArea></affiliation></author><author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name><affiliation><nlm:aff id="Aff10">Cancer Epidemiology Centre, The Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="Aff11">Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC Australia</nlm:aff><orgName type="university">Université de Melbourne</orgName><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Wiklund, Fredrik" sort="Wiklund, Fredrik" uniqKey="Wiklund F" first="Fredrik" last="Wiklund">Fredrik Wiklund</name><affiliation wicri:level="1"><nlm:aff id="Aff12">Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm</wicri:regionArea></affiliation></author><author><name sortKey="Gronberg, Henrik" sort="Gronberg, Henrik" uniqKey="Gronberg H" first="Henrik" last="Gronberg">Henrik Gronberg</name><affiliation wicri:level="1"><nlm:aff id="Aff12">Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm</wicri:regionArea></affiliation></author><author><name sortKey="Haiman, Christopher A" sort="Haiman, Christopher A" uniqKey="Haiman C" first="Christopher A." last="Haiman">Christopher A. Haiman</name><affiliation wicri:level="2"><nlm:aff id="Aff13">Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles</wicri:cityArea></affiliation></author><author><name sortKey="Schleutker, Johanna" sort="Schleutker, Johanna" uniqKey="Schleutker J" first="Johanna" last="Schleutker">Johanna Schleutker</name><affiliation wicri:level="1"><nlm:aff id="Aff14">Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Medical Biochemistry and Genetics, University of Turku, Turku</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff15">Institute of Biomedical Technology/BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute of Biomedical Technology/BioMediTech, University of Tampere and FimLab Laboratories, Tampere</wicri:regionArea></affiliation></author><author><name sortKey="Nordestgaard, B Rge G" sort="Nordestgaard, B Rge G" uniqKey="Nordestgaard B" first="B Rge G." last="Nordestgaard">B Rge G. Nordestgaard</name><affiliation wicri:level="1"><nlm:aff id="Aff16">Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, 2730 Herlev</wicri:regionArea></affiliation></author><author><name sortKey="Travis, Ruth C" sort="Travis, Ruth C" uniqKey="Travis R" first="Ruth C." last="Travis">Ruth C. Travis</name><affiliation wicri:level="1"><nlm:aff id="Aff17">Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford</wicri:regionArea></affiliation></author><author><name sortKey="Neal, David" sort="Neal, David" uniqKey="Neal D" first="David" last="Neal">David Neal</name><affiliation wicri:level="1"><nlm:aff id="Aff18">Surgical Oncology (Uro-Oncology: S4), University of Cambridge, Addenbrooke’s Hospital, Hills Road, Box 279, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Surgical Oncology (Uro-Oncology: S4), University of Cambridge, Addenbrooke’s Hospital, Hills Road, Box 279, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff19">Li Ka Shing Centre, Cancer Research UK Cambridge Research Institute, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Li Ka Shing Centre, Cancer Research UK Cambridge Research Institute, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Pashayan, Nora" sort="Pashayan, Nora" uniqKey="Pashayan N" first="Nora" last="Pashayan">Nora Pashayan</name><affiliation wicri:level="1"><nlm:aff id="Aff20">Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Worts Causeway, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Worts Causeway, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="4"><nlm:aff id="Aff41">Department of Applied Health Research, University College London, 1-19 Torrington Place, London, WC1E 7HB UK</nlm:aff><orgName type="university">University College de Londres</orgName><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Khaw, Kay Tee" sort="Khaw, Kay Tee" uniqKey="Khaw K" first="Kay-Tee" last="Khaw">Kay-Tee Khaw</name><affiliation wicri:level="4"><nlm:aff id="Aff21">Cambridge Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0SR UK</nlm:aff><orgName type="university">Université de Cambridge</orgName><country>Royaume-Uni</country><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation></author><author><name sortKey="Stanford, Janet L" sort="Stanford, Janet L" uniqKey="Stanford J" first="Janet L." last="Stanford">Janet L. Stanford</name><affiliation wicri:level="2"><nlm:aff id="Aff22">Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff23">Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Department of Epidemiology, School of Public Health, University of Washington, Seattle</wicri:cityArea></affiliation></author><author><name sortKey="Blot, William J" sort="Blot, William J" uniqKey="Blot W" first="William J." last="Blot">William J. Blot</name><affiliation wicri:level="2"><nlm:aff id="Aff24">International Epidemiology Institute, 1455 Research Blvd., Suite 550, Rockville, MD 20850 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>International Epidemiology Institute, 1455 Research Blvd., Suite 550, Rockville</wicri:cityArea></affiliation></author><author><name sortKey="Thibodeau, Stephen" sort="Thibodeau, Stephen" uniqKey="Thibodeau S" first="Stephen" last="Thibodeau">Stephen Thibodeau</name><affiliation wicri:level="2"><nlm:aff id="Aff25">Mayo Clinic, Rochester, MN USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>Mayo Clinic, Rochester</wicri:cityArea></affiliation></author><author><name sortKey="Maier, Christiane" sort="Maier, Christiane" uniqKey="Maier C" first="Christiane" last="Maier">Christiane Maier</name><affiliation wicri:level="1"><nlm:aff id="Aff26">Department of Urology, University Hospital Ulm, Ulm, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Urology, University Hospital Ulm, Ulm</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff27">Institute of Human Genetics, University Hospital Ulm, Ulm, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Human Genetics, University Hospital Ulm, Ulm</wicri:regionArea></affiliation></author><author><name sortKey="Kibel, Adam S" sort="Kibel, Adam S" uniqKey="Kibel A" first="Adam S." last="Kibel">Adam S. Kibel</name><affiliation wicri:level="2"><nlm:aff id="Aff28">Brigham and Women’s Hospital/Dana-Farber Cancer Institute, 45 Francis Street-ASB II-3, Boston, MA 02115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Brigham and Women’s Hospital/Dana-Farber Cancer Institute, 45 Francis Street-ASB II-3, Boston</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff29">Washington University, St. Louis, Missouri</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Missouri (État)</region></placeName><wicri:cityArea>Washington University, St. Louis</wicri:cityArea></affiliation></author><author><name sortKey="Cybulski, Cezary" sort="Cybulski, Cezary" uniqKey="Cybulski C" first="Cezary" last="Cybulski">Cezary Cybulski</name><affiliation wicri:level="1"><nlm:aff id="Aff30">International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland</nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea>International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin</wicri:regionArea></affiliation></author><author><name sortKey="Cannon Albright, Lisa" sort="Cannon Albright, Lisa" uniqKey="Cannon Albright L" first="Lisa" last="Cannon-Albright">Lisa Cannon-Albright</name><affiliation wicri:level="2"><nlm:aff id="Aff31">Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City</wicri:cityArea></affiliation></author><author><name sortKey="Brenner, Hermann" sort="Brenner, Hermann" uniqKey="Brenner H" first="Hermann" last="Brenner">Hermann Brenner</name><affiliation wicri:level="1"><nlm:aff id="Aff32">Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff33">Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff34">German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea></affiliation></author><author><name sortKey="Park, Jong" sort="Park, Jong" uniqKey="Park J" first="Jong" last="Park">Jong Park</name><affiliation wicri:level="2"><nlm:aff id="Aff35">Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr., Tampa, FL USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr., Tampa</wicri:cityArea></affiliation></author><author><name sortKey="Kaneva, Radka" sort="Kaneva, Radka" uniqKey="Kaneva R" first="Radka" last="Kaneva">Radka Kaneva</name><affiliation wicri:level="1"><nlm:aff id="Aff36">Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University Sofia, 2 Zdrave St, 1431 Sofia, Bulgaria</nlm:aff><country xml:lang="fr">Bulgarie</country><wicri:regionArea>Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University Sofia, 2 Zdrave St, 1431 Sofia</wicri:regionArea></affiliation></author><author><name sortKey="Batra, Jyotsna" sort="Batra, Jyotsna" uniqKey="Batra J" first="Jyotsna" last="Batra">Jyotsna Batra</name><affiliation><nlm:aff id="Aff37">Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD Australia</nlm:aff><wicri:noCountry code="subfield">QLD Australia</wicri:noCountry></affiliation></author><author><name sortKey="Teixeira, Manuel R" sort="Teixeira, Manuel R" uniqKey="Teixeira M" first="Manuel R." last="Teixeira">Manuel R. Teixeira</name><affiliation wicri:level="1"><nlm:aff id="Aff38">Department of Genetics, Portuguese Oncology Institute, Porto, Portugal</nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>Department of Genetics, Portuguese Oncology Institute, Porto</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff39">Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal</nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>Biomedical Sciences Institute (ICBAS), Porto University, Porto</wicri:regionArea></affiliation></author><author><name sortKey="Pandha, Hardev" sort="Pandha, Hardev" uniqKey="Pandha H" first="Hardev" last="Pandha">Hardev Pandha</name><affiliation><nlm:aff id="Aff40">The University of Surrey, Guildford, Surrey GU2 7XH UK</nlm:aff><wicri:noCountry code="subfield">Surrey GU2 7XH UK</wicri:noCountry></affiliation></author><author><name sortKey="Lathrop, Mark" sort="Lathrop, Mark" uniqKey="Lathrop M" first="Mark" last="Lathrop">Mark Lathrop</name><affiliation wicri:level="1"><nlm:aff id="Aff42">Commissariat à l’Energie Atomique, Center National de Génotypage, Evry, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Commissariat à l’Energie Atomique, Center National de Génotypage, Evry</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff43">McGill University-Génome Québec Innovation Centre, Montreal, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>McGill University-Génome Québec Innovation Centre, Montreal</wicri:regionArea></affiliation></author><author><name sortKey="Smith, George Davey" sort="Smith, George Davey" uniqKey="Smith G" first="George Davey" last="Smith">George Davey Smith</name><affiliation wicri:level="1"><nlm:aff id="Aff1">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, University of Bristol, Bristol</wicri:regionArea></affiliation></author><author><name sortKey="Martin, Richard M" sort="Martin, Richard M" uniqKey="Martin R" first="Richard M." last="Martin">Richard M. Martin</name><affiliation wicri:level="1"><nlm:aff id="Aff1">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, University of Bristol, Bristol</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff44">Bristol Nutrition Biomedical Research Unit, National Institute for Health Research, Bristol, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Bristol Nutrition Biomedical Research Unit, National Institute for Health Research, Bristol</wicri:regionArea></affiliation></author></analytic><series><title level="j">Cancer Causes & Control</title><idno type="ISSN">0957-5243</idno><idno type="eISSN">1573-7225</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Epidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality.</p></sec><sec><title>Methods</title><p>We conducted a case–control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man’s number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies.</p></sec><sec><title>Results</title><p>The genetic risk scores explained 6.31 and 1.46 % of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95 % CI 0.96, 1.00; <italic>p</italic> = 0.07). Genetic variants associated with increased height were not associated with prostate cancer incidence (OR 0.99; 95 % CI 0.97, 1.01; <italic>p</italic> = 0.23), but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in prostate cancer mortality among low-grade disease (<italic>p</italic> heterogeneity, low vs. high grade <0.001). Genetic variants associated with increased BMI were associated with an increase (OR 1.08; 95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade disease (<italic>p</italic> heterogeneity = 0.03).</p></sec><sec><title>Conclusions</title><p>We found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1007/s10552-015-0654-9) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Gronberg, H" uniqKey="Gronberg H">H Grönberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Discacciati, A" uniqKey="Discacciati A">A Discacciati</name></author><author><name sortKey="Orsini, N" uniqKey="Orsini N">N Orsini</name></author><author><name sortKey="Wolk, A" uniqKey="Wolk A">A Wolk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cao, Y" uniqKey="Cao Y">Y 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Cancer Causes Control</journal-id><journal-id journal-id-type="iso-abbrev">Cancer Causes Control</journal-id><journal-title-group><journal-title>Cancer Causes & Control</journal-title></journal-title-group><issn pub-type="ppub">0957-5243</issn><issn pub-type="epub">1573-7225</issn><publisher><publisher-name>Springer International Publishing</publisher-name><publisher-loc>Cham</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26387087</article-id><article-id pub-id-type="pmc">4596899</article-id><article-id pub-id-type="publisher-id">654</article-id><article-id pub-id-type="doi">10.1007/s10552-015-0654-9</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Paper</subject></subj-group></article-categories><title-group><article-title>The effects of height and BMI on prostate cancer incidence and mortality: a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Davies</surname><given-names>Neil M.</given-names></name><address><email>neil.davies@bristol.ac.uk</email></address><xref ref-type="aff" rid="Aff1"></xref><xref ref-type="aff" rid="Aff2"></xref></contrib><contrib contrib-type="author"><name><surname>Gaunt</surname><given-names>Tom R.</given-names></name><xref ref-type="aff" rid="Aff1"></xref><xref ref-type="aff" rid="Aff2"></xref></contrib><contrib contrib-type="author"><name><surname>Lewis</surname><given-names>Sarah J.</given-names></name><xref ref-type="aff" rid="Aff1"></xref><xref ref-type="aff" rid="Aff2"></xref></contrib><contrib contrib-type="author"><name><surname>Holly</surname><given-names>Jeff</given-names></name><xref ref-type="aff" rid="Aff3"></xref></contrib><contrib contrib-type="author"><name><surname>Donovan</surname><given-names>Jenny L.</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Hamdy</surname><given-names>Freddie C.</given-names></name><xref ref-type="aff" rid="Aff4"></xref></contrib><contrib contrib-type="author"><name><surname>Kemp</surname><given-names>John P.</given-names></name><xref ref-type="aff" rid="Aff2"></xref><xref ref-type="aff" rid="Aff5"></xref></contrib><contrib contrib-type="author"><name><surname>Eeles</surname><given-names>Rosalind</given-names></name><xref ref-type="aff" rid="Aff6"></xref><xref ref-type="aff" rid="Aff7"></xref></contrib><contrib contrib-type="author"><name><surname>Easton</surname><given-names>Doug</given-names></name><xref ref-type="aff" rid="Aff8"></xref></contrib><contrib contrib-type="author"><name><surname>Kote-Jarai</surname><given-names>Zsofia</given-names></name><xref ref-type="aff" rid="Aff6"></xref></contrib><contrib contrib-type="author"><name><surname>Al Olama</surname><given-names>Ali Amin</given-names></name><xref ref-type="aff" rid="Aff8"></xref></contrib><contrib contrib-type="author"><name><surname>Benlloch</surname><given-names>Sara</given-names></name><xref ref-type="aff" rid="Aff8"></xref></contrib><contrib contrib-type="author"><name><surname>Muir</surname><given-names>Kenneth</given-names></name><xref ref-type="aff" rid="Aff9"></xref></contrib><contrib contrib-type="author"><name><surname>Giles</surname><given-names>Graham G.</given-names></name><xref ref-type="aff" rid="Aff10"></xref><xref ref-type="aff" rid="Aff11"></xref></contrib><contrib contrib-type="author"><name><surname>Wiklund</surname><given-names>Fredrik</given-names></name><xref ref-type="aff" rid="Aff12"></xref></contrib><contrib contrib-type="author"><name><surname>Gronberg</surname><given-names>Henrik</given-names></name><xref ref-type="aff" rid="Aff12"></xref></contrib><contrib contrib-type="author"><name><surname>Haiman</surname><given-names>Christopher A.</given-names></name><xref ref-type="aff" rid="Aff13"></xref></contrib><contrib contrib-type="author"><name><surname>Schleutker</surname><given-names>Johanna</given-names></name><xref ref-type="aff" rid="Aff14"></xref><xref ref-type="aff" rid="Aff15"></xref></contrib><contrib contrib-type="author"><name><surname>Nordestgaard</surname><given-names>Børge G.</given-names></name><xref ref-type="aff" rid="Aff16"></xref></contrib><contrib contrib-type="author"><name><surname>Travis</surname><given-names>Ruth C.</given-names></name><xref ref-type="aff" rid="Aff17"></xref></contrib><contrib contrib-type="author"><name><surname>Neal</surname><given-names>David</given-names></name><xref ref-type="aff" rid="Aff18"></xref><xref ref-type="aff" rid="Aff19"></xref></contrib><contrib contrib-type="author"><name><surname>Pashayan</surname><given-names>Nora</given-names></name><xref ref-type="aff" rid="Aff20"></xref><xref ref-type="aff" rid="Aff41"></xref></contrib><contrib contrib-type="author"><name><surname>Khaw</surname><given-names>Kay-Tee</given-names></name><xref ref-type="aff" rid="Aff21"></xref></contrib><contrib contrib-type="author"><name><surname>Stanford</surname><given-names>Janet L.</given-names></name><xref ref-type="aff" rid="Aff22"></xref><xref ref-type="aff" rid="Aff23"></xref></contrib><contrib contrib-type="author"><name><surname>Blot</surname><given-names>William J.</given-names></name><xref ref-type="aff" rid="Aff24"></xref></contrib><contrib contrib-type="author"><name><surname>Thibodeau</surname><given-names>Stephen</given-names></name><xref ref-type="aff" rid="Aff25"></xref></contrib><contrib contrib-type="author"><name><surname>Maier</surname><given-names>Christiane</given-names></name><xref ref-type="aff" rid="Aff26"></xref><xref ref-type="aff" rid="Aff27"></xref></contrib><contrib contrib-type="author"><name><surname>Kibel</surname><given-names>Adam S.</given-names></name><xref ref-type="aff" rid="Aff28"></xref><xref ref-type="aff" rid="Aff29"></xref></contrib><contrib contrib-type="author"><name><surname>Cybulski</surname><given-names>Cezary</given-names></name><xref ref-type="aff" rid="Aff30"></xref></contrib><contrib contrib-type="author"><name><surname>Cannon-Albright</surname><given-names>Lisa</given-names></name><xref ref-type="aff" rid="Aff31"></xref></contrib><contrib contrib-type="author"><name><surname>Brenner</surname><given-names>Hermann</given-names></name><xref ref-type="aff" rid="Aff32"></xref><xref ref-type="aff" rid="Aff33"></xref><xref ref-type="aff" rid="Aff34"></xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>Jong</given-names></name><xref ref-type="aff" rid="Aff35"></xref></contrib><contrib contrib-type="author"><name><surname>Kaneva</surname><given-names>Radka</given-names></name><xref ref-type="aff" rid="Aff36"></xref></contrib><contrib contrib-type="author"><name><surname>Batra</surname><given-names>Jyotsna</given-names></name><xref ref-type="aff" rid="Aff37"></xref></contrib><contrib contrib-type="author"><name><surname>Teixeira</surname><given-names>Manuel R.</given-names></name><xref ref-type="aff" rid="Aff38"></xref><xref ref-type="aff" rid="Aff39"></xref></contrib><contrib contrib-type="author"><name><surname>Pandha</surname><given-names>Hardev</given-names></name><xref ref-type="aff" rid="Aff40"></xref></contrib><contrib contrib-type="author"><collab>PRACTICAL consortium</collab></contrib><contrib contrib-type="author"><name><surname>Lathrop</surname><given-names>Mark</given-names></name><xref ref-type="aff" rid="Aff42"></xref><xref ref-type="aff" rid="Aff43"></xref></contrib><contrib contrib-type="author"><name><surname>Smith</surname><given-names>George Davey</given-names></name><xref ref-type="aff" rid="Aff1"></xref><xref ref-type="aff" rid="Aff2"></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Martin</surname><given-names>Richard M.</given-names></name><address><phone>0117 9287321</phone><email>richard.martin@bristol.ac.uk</email></address><xref ref-type="aff" rid="Aff1"></xref><xref ref-type="aff" rid="Aff2"></xref><xref ref-type="aff" rid="Aff44"></xref></contrib><aff id="Aff1"><label></label>School of Social and Community Medicine, University of Bristol, Bristol, UK</aff><aff id="Aff2"><label></label>MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK</aff><aff id="Aff3"><label></label>School of Clinical Sciences, University of Bristol, Bristol, BS10 5NB UK</aff><aff id="Aff4"><label></label>Nuffield Department of Surgery, University of Oxford, Oxford, UK</aff><aff id="Aff5"><label></label>University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD Australia</aff><aff id="Aff6"><label></label>The Institute of Cancer Research, London, SM2 5NG UK</aff><aff id="Aff7"><label></label>The Royal Marsden NHS Foundation Trust, London, SW3 6JJ UK</aff><aff id="Aff8"><label></label>Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge, UK</aff><aff id="Aff9"><label></label>Institute of Population Health, University of Manchester, Manchester, UK</aff><aff id="Aff10"><label></label>Cancer Epidemiology Centre, The Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC Australia</aff><aff id="Aff11"><label></label>Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC Australia</aff><aff id="Aff12"><label></label>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden</aff><aff id="Aff13"><label></label>Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA USA</aff><aff id="Aff14"><label></label>Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland</aff><aff id="Aff15"><label></label>Institute of Biomedical Technology/BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland</aff><aff id="Aff16"><label></label>Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark</aff><aff id="Aff17"><label></label>Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK</aff><aff id="Aff18"><label></label>Surgical Oncology (Uro-Oncology: S4), University of Cambridge, Addenbrooke’s Hospital, Hills Road, Box 279, Cambridge, UK</aff><aff id="Aff19"><label></label>Li Ka Shing Centre, Cancer Research UK Cambridge Research Institute, Cambridge, UK</aff><aff id="Aff20"><label></label>Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Worts Causeway, Cambridge, UK</aff><aff id="Aff21"><label></label>Cambridge Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0SR UK</aff><aff id="Aff22"><label></label>Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA USA</aff><aff id="Aff23"><label></label>Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA USA</aff><aff id="Aff24"><label></label>International Epidemiology Institute, 1455 Research Blvd., Suite 550, Rockville, MD 20850 USA</aff><aff id="Aff25"><label></label>Mayo Clinic, Rochester, MN USA</aff><aff id="Aff26"><label></label>Department of Urology, University Hospital Ulm, Ulm, Germany</aff><aff id="Aff27"><label></label>Institute of Human Genetics, University Hospital Ulm, Ulm, Germany</aff><aff id="Aff28"><label></label>Brigham and Women’s Hospital/Dana-Farber Cancer Institute, 45 Francis Street-ASB II-3, Boston, MA 02115 USA</aff><aff id="Aff29"><label></label>Washington University, St. Louis, Missouri</aff><aff id="Aff30"><label></label>International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland</aff><aff id="Aff31"><label></label>Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT USA</aff><aff id="Aff32"><label></label>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany</aff><aff id="Aff33"><label></label>Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany</aff><aff id="Aff34"><label></label>German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany</aff><aff id="Aff35"><label></label>Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr., Tampa, FL USA</aff><aff id="Aff36"><label></label>Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University Sofia, 2 Zdrave St, 1431 Sofia, Bulgaria</aff><aff id="Aff37"><label></label>Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD Australia</aff><aff id="Aff38"><label></label>Department of Genetics, Portuguese Oncology Institute, Porto, Portugal</aff><aff id="Aff39"><label></label>Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal</aff><aff id="Aff40"><label></label>The University of Surrey, Guildford, Surrey GU2 7XH UK</aff><aff id="Aff41"><label></label>Department of Applied Health Research, University College London, 1-19 Torrington Place, London, WC1E 7HB UK</aff><aff id="Aff42"><label></label>Commissariat à l’Energie Atomique, Center National de Génotypage, Evry, France</aff><aff id="Aff43"><label></label>McGill University-Génome Québec Innovation Centre, Montreal, Canada</aff><aff id="Aff44"><label></label>Bristol Nutrition Biomedical Research Unit, National Institute for Health Research, Bristol, UK</aff></contrib-group><pub-date pub-type="epub"><day>19</day><month>9</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>19</day><month>9</month><year>2015</year></pub-date><pub-date pub-type="ppub"><year>2015</year></pub-date><volume>26</volume><issue>11</issue><fpage>1603</fpage><lpage>1616</lpage><history><date date-type="received"><day>9</day><month>4</month><year>2015</year></date><date date-type="accepted"><day>12</day><month>8</month><year>2015</year></date></history><permissions><copyright-statement>© The Author(s) 2015</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold>This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.</license-p></license></permissions><abstract id="Abs1"><sec><title>Background</title><p>Epidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality.</p></sec><sec><title>Methods</title><p>We conducted a case–control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man’s number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies.</p></sec><sec><title>Results</title><p>The genetic risk scores explained 6.31 and 1.46 % of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95 % CI 0.96, 1.00; <italic>p</italic> = 0.07). Genetic variants associated with increased height were not associated with prostate cancer incidence (OR 0.99; 95 % CI 0.97, 1.01; <italic>p</italic> = 0.23), but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in prostate cancer mortality among low-grade disease (<italic>p</italic> heterogeneity, low vs. high grade <0.001). Genetic variants associated with increased BMI were associated with an increase (OR 1.08; 95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade disease (<italic>p</italic> heterogeneity = 0.03).</p></sec><sec><title>Conclusions</title><p>We found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1007/s10552-015-0654-9) contains supplementary material, which is available to authorized users.</p></sec></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>Height</kwd><kwd>Body mass index</kwd><kwd>Prostate cancer</kwd><kwd>Mendelian randomization</kwd><kwd>Single nucleotide polymorphisms</kwd><kwd>Instrumental variables analysis</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© Springer International Publishing Switzerland 2015</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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