Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels.
Identifieur interne : 002340 ( Main/Exploration ); précédent : 002339; suivant : 002341Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels.
Auteurs : Carolina Bonilla [Royaume-Uni] ; Sarah J. Lewis [Royaume-Uni] ; Mari-Anne Rowlands [Royaume-Uni] ; Tom R. Gaunt [Royaume-Uni] ; George Davey Smith [Royaume-Uni] ; David Gunnell [Royaume-Uni] ; Tom Palmer [Royaume-Uni] ; Jenny L. Donovan [Royaume-Uni] ; Freddie C. Hamdy [Royaume-Uni] ; David E. Neal [Royaume-Uni] ; Rosalind Eeles [Royaume-Uni] ; Doug Easton [Royaume-Uni] ; Zsofia Kote-Jarai [Royaume-Uni] ; Ali Amin Al Olama [Royaume-Uni] ; Sara Benlloch [Royaume-Uni] ; Kenneth Muir [Royaume-Uni] ; Graham G. Giles [Australie] ; Fredrik Wiklund [Suède] ; Henrik Grönberg [Suède] ; Christopher A. Haiman [États-Unis] ; Johanna Schleutker [Finlande] ; B Rge G. Nordestgaard [Danemark] ; Ruth C. Travis [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 ; Cezary Cybulski [Pologne] ; Lisa Cannon-Albright [États-Unis] ; Hermann Brenner [Allemagne] ; Jong Park [États-Unis] ; Radka Kaneva [Bulgarie] ; Jyotsna Batra [Australie] ; Manuel R. Teixeira [Portugal] ; Hardev Pandha [Royaume-Uni] ; Mark Lathrop [France] ; Richard M. Martin [Royaume-Uni] ; Jeff M P. Holly [Royaume-Uni]Source :
- International journal of cancer [ 1097-0215 ] ; 2016.
Descripteurs français
- KwdFr :
- Adulte d'âge moyen, Analyse de randomisation mendélienne (), Grading des tumeurs, Humains, Mâle, Polymorphisme de nucléotide simple, Protéines de liaison aux IGF (génétique), Protéines de liaison aux IGF (métabolisme), Royaume-Uni (épidémiologie), Somatomédines (génétique), Somatomédines (métabolisme), Stade de la tumeur, Sujet âgé, Tumeurs de la prostate (anatomopathologie), Tumeurs de la prostate (génétique), Tumeurs de la prostate (sang), Tumeurs de la prostate (épidémiologie), Étude d'association pangénomique, Études cas-témoins, Études longitudinales.
- MESH :
- anatomopathologie : Tumeurs de la prostate.
- génétique : Protéines de liaison aux IGF, Somatomédines, Tumeurs de la prostate.
- métabolisme : Protéines de liaison aux IGF, Somatomédines.
- sang : Tumeurs de la prostate.
- épidémiologie : Royaume-Uni, Tumeurs de la prostate.
- Adulte d'âge moyen, Analyse de randomisation mendélienne, Grading des tumeurs, Humains, Mâle, Polymorphisme de nucléotide simple, Stade de la tumeur, Sujet âgé, Étude d'association pangénomique, Études cas-témoins, Études longitudinales.
English descriptors
- KwdEn :
- Aged, Case-Control Studies, Genome-Wide Association Study, Humans, Insulin-Like Growth Factor Binding Proteins (genetics), Insulin-Like Growth Factor Binding Proteins (metabolism), Longitudinal Studies, Male, Mendelian Randomization Analysis (methods), Middle Aged, Neoplasm Grading, Neoplasm Staging, Polymorphism, Single Nucleotide, Prostatic Neoplasms (blood), Prostatic Neoplasms (epidemiology), Prostatic Neoplasms (genetics), Prostatic Neoplasms (pathology), Somatomedins (genetics), Somatomedins (metabolism), United Kingdom (epidemiology).
- MESH :
- chemical , genetics : Insulin-Like Growth Factor Binding Proteins, Somatomedins.
- chemical , metabolism : Insulin-Like Growth Factor Binding Proteins, Somatomedins.
- blood : Prostatic Neoplasms.
- epidemiology : Prostatic Neoplasms, United Kingdom.
- genetics : Prostatic Neoplasms.
- methods : Mendelian Randomization Analysis.
- pathology : Prostatic Neoplasms.
- Aged, Case-Control Studies, Genome-Wide Association Study, Humans, Longitudinal Studies, Male, Middle Aged, Neoplasm Grading, Neoplasm Staging, Polymorphism, Single Nucleotide.
Abstract
Circulating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs. high (≥ 7) Gleason grade, localised vs. advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs. low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker.
DOI: 10.1002/ijc.30206
PubMed: 27225428
Affiliations:
- Allemagne, Australie, Bulgarie, Danemark, Finlande, France, Pologne, Portugal, Royaume-Uni, Suède, États-Unis
- Angleterre, Angleterre de l'Est, Bade-Wurtemberg, Californie, District de Karlsruhe, Finlande occidentale, Floride, Maryland, Minnesota, Oxfordshire, Svealand, Utah, Washington (État), Île-de-France
- Cambridge, Heidelberg, Oxford, Stockholm, Turku, Évry (Essonne)
- Université d'Oxford, Université de Cambridge, Université de Turku
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Le document en format XML
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Giles</name><affiliation wicri:level="1"><nlm:affiliation>The Cancer Council Victoria, 615 St. Kilda Road, Melbourne, Victoria, 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The Cancer Council Victoria, 615 St. Kilda Road, Melbourne, Victoria, 3004</wicri:regionArea><wicri:noRegion>3004</wicri:noRegion></affiliation></author><author><name sortKey="Wiklund, Fredrik" sort="Wiklund, Fredrik" uniqKey="Wiklund F" first="Fredrik" last="Wiklund">Fredrik Wiklund</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Gronberg, Henrik" sort="Gronberg, Henrik" uniqKey="Gronberg H" first="Henrik" last="Grönberg">Henrik Grönberg</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></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:affiliation>Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.</nlm:affiliation><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="4"><nlm:affiliation>Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Medical Biochemistry and Genetics, University of Turku, Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region><settlement type="city">Turku</settlement></placeName><orgName type="university">Université de Turku</orgName></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:affiliation>Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev, DK, 2730, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev, DK, 2730</wicri:regionArea><wicri:noRegion>2730</wicri:noRegion></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="4"><nlm:affiliation>Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Pashayan, Nora" sort="Pashayan, Nora" uniqKey="Pashayan N" first="Nora" last="Pashayan">Nora Pashayan</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><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="Khaw, Kay Tee" sort="Khaw, Kay Tee" uniqKey="Khaw K" first="Kay-Tee" last="Khaw">Kay-Tee Khaw</name><affiliation wicri:level="4"><nlm:affiliation>Forvie Site, Cambridge Institute of Public Health, University of Cambridge, Robinson Way, Cambridge, CB2 0SR, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Forvie Site, Cambridge Institute of Public Health, University of Cambridge, Robinson Way, Cambridge, CB2 0SR</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><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:affiliation>Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.</nlm:affiliation><country xml:lang="fr">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></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:affiliation>International Epidemiology Institute, 1455 Research Blvd, Suite 550, Rockville, Maryland.</nlm:affiliation><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:affiliation>Mayo Clinic, Rochester, Minnesota.</nlm:affiliation><country xml:lang="fr">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:affiliation>Department of Urology, University Hospital Ulm, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Urology, University Hospital Ulm</wicri:regionArea><wicri:noRegion>University Hospital Ulm</wicri:noRegion><wicri:noRegion>University Hospital Ulm</wicri:noRegion><wicri:noRegion>University Hospital Ulm</wicri:noRegion></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><nlm:affiliation>Brigham and Women's Hospital/Dana-Farber Cancer Institute, 45 Francis Street-ASB II-3, Boston, Massachussets.</nlm:affiliation><wicri:noCountry code="subField">Massachussets</wicri:noCountry></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:affiliation>International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.</nlm:affiliation><country xml:lang="fr">Pologne</country><wicri:regionArea>International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin</wicri:regionArea><wicri:noRegion>Szczecin</wicri:noRegion></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:affiliation>Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah.</nlm:affiliation><country xml:lang="fr">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="3"><nlm:affiliation>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></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:affiliation>Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr, Tampa, Florida.</nlm:affiliation><country xml:lang="fr">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:affiliation>Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University - Sofia, 2 Zdrave St, Sofia, 1431, Bulgaria.</nlm:affiliation><country xml:lang="fr">Bulgarie</country><wicri:regionArea>Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University - Sofia, 2 Zdrave St, Sofia, 1431</wicri:regionArea><wicri:noRegion>1431</wicri:noRegion></affiliation></author><author><name sortKey="Batra, Jyotsna" sort="Batra, Jyotsna" uniqKey="Batra J" first="Jyotsna" last="Batra">Jyotsna Batra</name><affiliation wicri:level="1"><nlm:affiliation>Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></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:affiliation>Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.</nlm:affiliation><country xml:lang="fr">Portugal</country><wicri:regionArea>Department of Genetics, Portuguese Oncology Institute, Porto</wicri:regionArea><wicri:noRegion>Porto</wicri:noRegion></affiliation></author><author><name sortKey="Pandha, Hardev" sort="Pandha, Hardev" uniqKey="Pandha H" first="Hardev" last="Pandha">Hardev Pandha</name><affiliation wicri:level="1"><nlm:affiliation>The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The University of Surrey, Guildford, Surrey, GU2 7XH</wicri:regionArea><wicri:noRegion>GU2 7XH</wicri:noRegion></affiliation></author><author><name sortKey="Lathrop, Mark" sort="Lathrop, Mark" uniqKey="Lathrop M" first="Mark" last="Lathrop">Mark Lathrop</name><affiliation wicri:level="3"><nlm:affiliation>Commissariat à L'Energie Atomique, Center National De Génotypage, Evry, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Commissariat à L'Energie Atomique, Center National De Génotypage, Evry</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Évry (Essonne)</settlement></placeName></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:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Holly, Jeff M P" sort="Holly, Jeff M P" uniqKey="Holly J" first="Jeff M P" last="Holly">Jeff M P. Holly</name><affiliation wicri:level="1"><nlm:affiliation>NIHR Bristol Biomedical Research Unit in Nutrition, Bristol, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NIHR Bristol Biomedical Research Unit in Nutrition, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27225428</idno><idno type="pmid">27225428</idno><idno type="doi">10.1002/ijc.30206</idno><idno type="wicri:Area/PubMed/Corpus">001761</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001761</idno><idno type="wicri:Area/PubMed/Curation">001738</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001738</idno><idno type="wicri:Area/PubMed/Checkpoint">001738</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001738</idno><idno type="wicri:Area/Ncbi/Merge">003598</idno><idno type="wicri:Area/Ncbi/Curation">003598</idno><idno type="wicri:Area/Ncbi/Checkpoint">003598</idno><idno type="wicri:Area/Main/Merge">002339</idno><idno type="wicri:Area/Main/Curation">002340</idno><idno type="wicri:Area/Main/Exploration">002340</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels.</title><author><name sortKey="Bonilla, Carolina" sort="Bonilla, Carolina" uniqKey="Bonilla C" first="Carolina" last="Bonilla">Carolina Bonilla</name><affiliation wicri:level="1"><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></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:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Rowlands, Mari Anne" sort="Rowlands, Mari Anne" uniqKey="Rowlands M" first="Mari-Anne" last="Rowlands">Mari-Anne Rowlands</name><affiliation wicri:level="1"><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></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:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Davey Smith, George" sort="Davey Smith, George" uniqKey="Davey Smith G" first="George" last="Davey Smith">George Davey Smith</name><affiliation wicri:level="1"><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Gunnell, David" sort="Gunnell, David" uniqKey="Gunnell D" first="David" last="Gunnell">David Gunnell</name><affiliation wicri:level="1"><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Palmer, Tom" sort="Palmer, Tom" uniqKey="Palmer T" first="Tom" last="Palmer">Tom Palmer</name><affiliation wicri:level="1"><nlm:affiliation>Department of Mathematics and Statistics, Lancaster University, Lancaster, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Mathematics and Statistics, Lancaster University, Lancaster</wicri:regionArea><wicri:noRegion>Lancaster</wicri:noRegion></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:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></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="4"><nlm:affiliation>Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Nuffield Department of Surgery, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Neal, David E" sort="Neal, David E" uniqKey="Neal D" first="David E" last="Neal">David E. Neal</name><affiliation wicri:level="4"><nlm:affiliation>Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Nuffield Department of Surgery, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Eeles, Rosalind" sort="Eeles, Rosalind" uniqKey="Eeles R" first="Rosalind" last="Eeles">Rosalind Eeles</name><affiliation wicri:level="1"><nlm:affiliation>The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG</wicri:regionArea><wicri:noRegion>SM2 5NG</wicri:noRegion></affiliation></author><author><name sortKey="Easton, Doug" sort="Easton, Doug" uniqKey="Easton D" first="Doug" last="Easton">Doug Easton</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><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="Kote Jarai, Zsofia" sort="Kote Jarai, Zsofia" uniqKey="Kote Jarai Z" first="Zsofia" last="Kote-Jarai">Zsofia Kote-Jarai</name><affiliation wicri:level="1"><nlm:affiliation>The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG</wicri:regionArea><wicri:noRegion>SM2 5NG</wicri:noRegion></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="4"><nlm:affiliation>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><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="Benlloch, Sara" sort="Benlloch, Sara" uniqKey="Benlloch S" first="Sara" last="Benlloch">Sara Benlloch</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><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="Muir, Kenneth" sort="Muir, Kenneth" uniqKey="Muir K" first="Kenneth" last="Muir">Kenneth Muir</name><affiliation wicri:level="1"><nlm:affiliation>University of Warwick, Coventry, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>University of Warwick, Coventry</wicri:regionArea><wicri:noRegion>Coventry</wicri:noRegion></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 wicri:level="1"><nlm:affiliation>The Cancer Council Victoria, 615 St. Kilda Road, Melbourne, Victoria, 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The Cancer Council Victoria, 615 St. Kilda Road, Melbourne, Victoria, 3004</wicri:regionArea><wicri:noRegion>3004</wicri:noRegion></affiliation></author><author><name sortKey="Wiklund, Fredrik" sort="Wiklund, Fredrik" uniqKey="Wiklund F" first="Fredrik" last="Wiklund">Fredrik Wiklund</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Gronberg, Henrik" sort="Gronberg, Henrik" uniqKey="Gronberg H" first="Henrik" last="Grönberg">Henrik Grönberg</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></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:affiliation>Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.</nlm:affiliation><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="4"><nlm:affiliation>Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Medical Biochemistry and Genetics, University of Turku, Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region><settlement type="city">Turku</settlement></placeName><orgName type="university">Université de Turku</orgName></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:affiliation>Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev, DK, 2730, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev, DK, 2730</wicri:regionArea><wicri:noRegion>2730</wicri:noRegion></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="4"><nlm:affiliation>Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Pashayan, Nora" sort="Pashayan, Nora" uniqKey="Pashayan N" first="Nora" last="Pashayan">Nora Pashayan</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><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="Khaw, Kay Tee" sort="Khaw, Kay Tee" uniqKey="Khaw K" first="Kay-Tee" last="Khaw">Kay-Tee Khaw</name><affiliation wicri:level="4"><nlm:affiliation>Forvie Site, Cambridge Institute of Public Health, University of Cambridge, Robinson Way, Cambridge, CB2 0SR, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Forvie Site, Cambridge Institute of Public Health, University of Cambridge, Robinson Way, Cambridge, CB2 0SR</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><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:affiliation>Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.</nlm:affiliation><country xml:lang="fr">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></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:affiliation>International Epidemiology Institute, 1455 Research Blvd, Suite 550, Rockville, Maryland.</nlm:affiliation><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:affiliation>Mayo Clinic, Rochester, Minnesota.</nlm:affiliation><country xml:lang="fr">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:affiliation>Department of Urology, University Hospital Ulm, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Urology, University Hospital Ulm</wicri:regionArea><wicri:noRegion>University Hospital Ulm</wicri:noRegion><wicri:noRegion>University Hospital Ulm</wicri:noRegion><wicri:noRegion>University Hospital Ulm</wicri:noRegion></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><nlm:affiliation>Brigham and Women's Hospital/Dana-Farber Cancer Institute, 45 Francis Street-ASB II-3, Boston, Massachussets.</nlm:affiliation><wicri:noCountry code="subField">Massachussets</wicri:noCountry></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:affiliation>International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.</nlm:affiliation><country xml:lang="fr">Pologne</country><wicri:regionArea>International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin</wicri:regionArea><wicri:noRegion>Szczecin</wicri:noRegion></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:affiliation>Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah.</nlm:affiliation><country xml:lang="fr">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="3"><nlm:affiliation>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></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:affiliation>Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr, Tampa, Florida.</nlm:affiliation><country xml:lang="fr">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:affiliation>Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University - Sofia, 2 Zdrave St, Sofia, 1431, Bulgaria.</nlm:affiliation><country xml:lang="fr">Bulgarie</country><wicri:regionArea>Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University - Sofia, 2 Zdrave St, Sofia, 1431</wicri:regionArea><wicri:noRegion>1431</wicri:noRegion></affiliation></author><author><name sortKey="Batra, Jyotsna" sort="Batra, Jyotsna" uniqKey="Batra J" first="Jyotsna" last="Batra">Jyotsna Batra</name><affiliation wicri:level="1"><nlm:affiliation>Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></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:affiliation>Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.</nlm:affiliation><country xml:lang="fr">Portugal</country><wicri:regionArea>Department of Genetics, Portuguese Oncology Institute, Porto</wicri:regionArea><wicri:noRegion>Porto</wicri:noRegion></affiliation></author><author><name sortKey="Pandha, Hardev" sort="Pandha, Hardev" uniqKey="Pandha H" first="Hardev" last="Pandha">Hardev Pandha</name><affiliation wicri:level="1"><nlm:affiliation>The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The University of Surrey, Guildford, Surrey, GU2 7XH</wicri:regionArea><wicri:noRegion>GU2 7XH</wicri:noRegion></affiliation></author><author><name sortKey="Lathrop, Mark" sort="Lathrop, Mark" uniqKey="Lathrop M" first="Mark" last="Lathrop">Mark Lathrop</name><affiliation wicri:level="3"><nlm:affiliation>Commissariat à L'Energie Atomique, Center National De Génotypage, Evry, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Commissariat à L'Energie Atomique, Center National De Génotypage, Evry</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Évry (Essonne)</settlement></placeName></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:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Holly, Jeff M P" sort="Holly, Jeff M P" uniqKey="Holly J" first="Jeff M P" last="Holly">Jeff M P. Holly</name><affiliation wicri:level="1"><nlm:affiliation>NIHR Bristol Biomedical Research Unit in Nutrition, Bristol, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NIHR Bristol Biomedical Research Unit in Nutrition, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author></analytic><series><title level="j">International journal of cancer</title><idno type="eISSN">1097-0215</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Case-Control Studies</term><term>Genome-Wide Association Study</term><term>Humans</term><term>Insulin-Like Growth Factor Binding Proteins (genetics)</term><term>Insulin-Like Growth Factor Binding Proteins (metabolism)</term><term>Longitudinal Studies</term><term>Male</term><term>Mendelian Randomization Analysis (methods)</term><term>Middle Aged</term><term>Neoplasm Grading</term><term>Neoplasm Staging</term><term>Polymorphism, Single Nucleotide</term><term>Prostatic Neoplasms (blood)</term><term>Prostatic Neoplasms (epidemiology)</term><term>Prostatic Neoplasms (genetics)</term><term>Prostatic Neoplasms (pathology)</term><term>Somatomedins (genetics)</term><term>Somatomedins (metabolism)</term><term>United Kingdom (epidemiology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Analyse de randomisation mendélienne ()</term><term>Grading des tumeurs</term><term>Humains</term><term>Mâle</term><term>Polymorphisme de nucléotide simple</term><term>Protéines de liaison aux IGF (génétique)</term><term>Protéines de liaison aux IGF (métabolisme)</term><term>Royaume-Uni (épidémiologie)</term><term>Somatomédines (génétique)</term><term>Somatomédines (métabolisme)</term><term>Stade de la tumeur</term><term>Sujet âgé</term><term>Tumeurs de la prostate (anatomopathologie)</term><term>Tumeurs de la prostate (génétique)</term><term>Tumeurs de la prostate (sang)</term><term>Tumeurs de la prostate (épidémiologie)</term><term>Étude d'association pangénomique</term><term>Études cas-témoins</term><term>Études longitudinales</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Insulin-Like Growth Factor Binding Proteins</term><term>Somatomedins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Insulin-Like Growth Factor Binding Proteins</term><term>Somatomedins</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Tumeurs de la prostate</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Prostatic Neoplasms</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Prostatic Neoplasms</term><term>United Kingdom</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Prostatic Neoplasms</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Protéines de liaison aux IGF</term><term>Somatomédines</term><term>Tumeurs de la prostate</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Mendelian Randomization Analysis</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéines de liaison aux IGF</term><term>Somatomédines</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Prostatic Neoplasms</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Tumeurs de la prostate</term></keywords><keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr"><term>Royaume-Uni</term><term>Tumeurs de la prostate</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Case-Control Studies</term><term>Genome-Wide Association Study</term><term>Humans</term><term>Longitudinal Studies</term><term>Male</term><term>Middle Aged</term><term>Neoplasm Grading</term><term>Neoplasm Staging</term><term>Polymorphism, Single Nucleotide</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Analyse de randomisation mendélienne</term><term>Grading des tumeurs</term><term>Humains</term><term>Mâle</term><term>Polymorphisme de nucléotide simple</term><term>Stade de la tumeur</term><term>Sujet âgé</term><term>Étude d'association pangénomique</term><term>Études cas-témoins</term><term>Études longitudinales</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Circulating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs. high (≥ 7) Gleason grade, localised vs. advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs. low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Bulgarie</li><li>Danemark</li><li>Finlande</li><li>France</li><li>Pologne</li><li>Portugal</li><li>Royaume-Uni</li><li>Suède</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Angleterre de l'Est</li><li>Bade-Wurtemberg</li><li>Californie</li><li>District de Karlsruhe</li><li>Finlande occidentale</li><li>Floride</li><li>Maryland</li><li>Minnesota</li><li>Oxfordshire</li><li>Svealand</li><li>Utah</li><li>Washington (État)</li><li>Île-de-France</li></region><settlement><li>Cambridge</li><li>Heidelberg</li><li>Oxford</li><li>Stockholm</li><li>Turku</li><li>Évry (Essonne)</li></settlement><orgName><li>Université d'Oxford</li><li>Université de Cambridge</li><li>Université de Turku</li></orgName></list><tree><noCountry><name sortKey="Kibel, Adam S" sort="Kibel, Adam S" uniqKey="Kibel A" first="Adam S" last="Kibel">Adam S. Kibel</name></noCountry><country name="Royaume-Uni"><noRegion><name sortKey="Bonilla, Carolina" sort="Bonilla, Carolina" uniqKey="Bonilla C" first="Carolina" last="Bonilla">Carolina Bonilla</name></noRegion><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><name sortKey="Benlloch, Sara" sort="Benlloch, Sara" uniqKey="Benlloch S" first="Sara" last="Benlloch">Sara Benlloch</name><name sortKey="Davey Smith, George" sort="Davey Smith, George" uniqKey="Davey Smith G" first="George" last="Davey Smith">George Davey Smith</name><name sortKey="Donovan, Jenny L" sort="Donovan, Jenny L" uniqKey="Donovan J" first="Jenny L" last="Donovan">Jenny L. Donovan</name><name sortKey="Easton, Doug" sort="Easton, Doug" uniqKey="Easton D" first="Doug" last="Easton">Doug Easton</name><name sortKey="Eeles, Rosalind" sort="Eeles, Rosalind" uniqKey="Eeles R" first="Rosalind" last="Eeles">Rosalind Eeles</name><name sortKey="Gaunt, Tom R" sort="Gaunt, Tom R" uniqKey="Gaunt T" first="Tom R" last="Gaunt">Tom R. Gaunt</name><name sortKey="Gunnell, David" sort="Gunnell, David" uniqKey="Gunnell D" first="David" last="Gunnell">David Gunnell</name><name sortKey="Hamdy, Freddie C" sort="Hamdy, Freddie C" uniqKey="Hamdy F" first="Freddie C" last="Hamdy">Freddie C. Hamdy</name><name sortKey="Holly, Jeff M P" sort="Holly, Jeff M P" uniqKey="Holly J" first="Jeff M P" last="Holly">Jeff M P. Holly</name><name sortKey="Khaw, Kay Tee" sort="Khaw, Kay Tee" uniqKey="Khaw K" first="Kay-Tee" last="Khaw">Kay-Tee Khaw</name><name sortKey="Kote Jarai, Zsofia" sort="Kote Jarai, Zsofia" uniqKey="Kote Jarai Z" first="Zsofia" last="Kote-Jarai">Zsofia Kote-Jarai</name><name sortKey="Lewis, Sarah J" sort="Lewis, Sarah J" uniqKey="Lewis S" first="Sarah J" last="Lewis">Sarah J. Lewis</name><name sortKey="Martin, Richard M" sort="Martin, Richard M" uniqKey="Martin R" first="Richard M" last="Martin">Richard M. Martin</name><name sortKey="Muir, Kenneth" sort="Muir, Kenneth" uniqKey="Muir K" first="Kenneth" last="Muir">Kenneth Muir</name><name sortKey="Neal, David E" sort="Neal, David E" uniqKey="Neal D" first="David E" last="Neal">David E. Neal</name><name sortKey="Palmer, Tom" sort="Palmer, Tom" uniqKey="Palmer T" first="Tom" last="Palmer">Tom Palmer</name><name sortKey="Pandha, Hardev" sort="Pandha, Hardev" uniqKey="Pandha H" first="Hardev" last="Pandha">Hardev Pandha</name><name sortKey="Pashayan, Nora" sort="Pashayan, Nora" uniqKey="Pashayan N" first="Nora" last="Pashayan">Nora Pashayan</name><name sortKey="Rowlands, Mari Anne" sort="Rowlands, Mari Anne" uniqKey="Rowlands M" first="Mari-Anne" last="Rowlands">Mari-Anne Rowlands</name><name sortKey="Travis, Ruth C" sort="Travis, Ruth C" uniqKey="Travis R" first="Ruth C" last="Travis">Ruth C. Travis</name></country><country name="Australie"><noRegion><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G" last="Giles">Graham G. Giles</name></noRegion><name sortKey="Batra, Jyotsna" sort="Batra, Jyotsna" uniqKey="Batra J" first="Jyotsna" last="Batra">Jyotsna Batra</name></country><country name="Suède"><region name="Svealand"><name sortKey="Wiklund, Fredrik" sort="Wiklund, Fredrik" uniqKey="Wiklund F" first="Fredrik" last="Wiklund">Fredrik Wiklund</name></region><name sortKey="Gronberg, Henrik" sort="Gronberg, Henrik" uniqKey="Gronberg H" first="Henrik" last="Grönberg">Henrik Grönberg</name></country><country name="États-Unis"><region name="Californie"><name sortKey="Haiman, Christopher A" sort="Haiman, Christopher A" uniqKey="Haiman C" first="Christopher A" last="Haiman">Christopher A. Haiman</name></region><name sortKey="Blot, William J" sort="Blot, William J" uniqKey="Blot W" first="William J" last="Blot">William J. Blot</name><name sortKey="Cannon Albright, Lisa" sort="Cannon Albright, Lisa" uniqKey="Cannon Albright L" first="Lisa" last="Cannon-Albright">Lisa Cannon-Albright</name><name sortKey="Park, Jong" sort="Park, Jong" uniqKey="Park J" first="Jong" last="Park">Jong Park</name><name sortKey="Stanford, Janet L" sort="Stanford, Janet L" uniqKey="Stanford J" first="Janet L" last="Stanford">Janet L. Stanford</name><name sortKey="Thibodeau, Stephen" sort="Thibodeau, Stephen" uniqKey="Thibodeau S" first="Stephen" last="Thibodeau">Stephen Thibodeau</name></country><country name="Finlande"><region name="Finlande occidentale"><name sortKey="Schleutker, Johanna" sort="Schleutker, Johanna" uniqKey="Schleutker J" first="Johanna" last="Schleutker">Johanna Schleutker</name></region></country><country name="Danemark"><noRegion><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></noRegion></country><country name="Allemagne"><noRegion><name sortKey="Maier, Christiane" sort="Maier, Christiane" uniqKey="Maier C" first="Christiane" last="Maier">Christiane Maier</name></noRegion><name sortKey="Brenner, Hermann" sort="Brenner, Hermann" uniqKey="Brenner H" first="Hermann" last="Brenner">Hermann Brenner</name></country><country name="Pologne"><noRegion><name sortKey="Cybulski, Cezary" sort="Cybulski, Cezary" uniqKey="Cybulski C" first="Cezary" last="Cybulski">Cezary Cybulski</name></noRegion></country><country name="Bulgarie"><noRegion><name sortKey="Kaneva, Radka" sort="Kaneva, Radka" uniqKey="Kaneva R" first="Radka" last="Kaneva">Radka Kaneva</name></noRegion></country><country name="Portugal"><noRegion><name sortKey="Teixeira, Manuel R" sort="Teixeira, Manuel R" uniqKey="Teixeira M" first="Manuel R" last="Teixeira">Manuel R. Teixeira</name></noRegion></country><country name="France"><region name="Île-de-France"><name sortKey="Lathrop, Mark" sort="Lathrop, Mark" uniqKey="Lathrop M" first="Mark" last="Lathrop">Mark Lathrop</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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