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 : 001761 ( PubMed/Corpus ); précédent : 001760; suivant : 001762Assessing 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 ; Sarah J. Lewis ; Mari-Anne Rowlands ; Tom R. Gaunt ; George Davey Smith ; David Gunnell ; Tom Palmer ; Jenny L. Donovan ; Freddie C. Hamdy ; David E. Neal ; Rosalind Eeles ; Doug Easton ; Zsofia Kote-Jarai ; Ali Amin Al Olama ; Sara Benlloch ; Kenneth Muir ; Graham G. Giles ; Fredrik Wiklund ; Henrik Grönberg ; Christopher A. Haiman ; Johanna Schleutker ; B Rge G. Nordestgaard ; Ruth C. Travis ; Nora Pashayan ; Kay-Tee Khaw ; Janet L. Stanford ; William J. Blot ; Stephen Thibodeau ; Christiane Maier ; Adam S. Kibel ; Cezary Cybulski ; Lisa Cannon-Albright ; Hermann Brenner ; Jong Park ; Radka Kaneva ; Jyotsna Batra ; Manuel R. Teixeira ; Hardev Pandha ; Mark Lathrop ; Richard M. Martin ; Jeff M P. HollySource :
- International journal of cancer [ 1097-0215 ] ; 2016.
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
Links to Exploration step
pubmed:27225428Le document en format XML
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Lewis</name><affiliation><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation></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><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation></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><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation></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><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Gunnell, David" sort="Gunnell, David" uniqKey="Gunnell D" first="David" last="Gunnell">David Gunnell</name><affiliation><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Palmer, Tom" sort="Palmer, Tom" uniqKey="Palmer T" first="Tom" last="Palmer">Tom Palmer</name><affiliation><nlm:affiliation>Department of Mathematics and Statistics, Lancaster University, Lancaster, United Kingdom.</nlm:affiliation></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><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation></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><nlm:affiliation>Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom.</nlm:affiliation></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><nlm:affiliation>Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Eeles, Rosalind" sort="Eeles, Rosalind" uniqKey="Eeles R" first="Rosalind" last="Eeles">Rosalind Eeles</name><affiliation><nlm:affiliation>The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Easton, Doug" sort="Easton, Doug" uniqKey="Easton D" first="Doug" last="Easton">Doug Easton</name><affiliation><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></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:affiliation>The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, United Kingdom.</nlm:affiliation></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><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></affiliation></author><author><name sortKey="Benlloch, Sara" sort="Benlloch, Sara" uniqKey="Benlloch S" first="Sara" last="Benlloch">Sara Benlloch</name><affiliation><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></affiliation></author><author><name sortKey="Muir, Kenneth" sort="Muir, Kenneth" uniqKey="Muir K" first="Kenneth" last="Muir">Kenneth Muir</name><affiliation><nlm:affiliation>University of Warwick, Coventry, United Kingdom.</nlm:affiliation></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:affiliation>The Cancer Council Victoria, 615 St. Kilda Road, Melbourne, Victoria, 3004, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Wiklund, Fredrik" sort="Wiklund, Fredrik" uniqKey="Wiklund F" first="Fredrik" last="Wiklund">Fredrik Wiklund</name><affiliation><nlm:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Gronberg, Henrik" sort="Gronberg, Henrik" uniqKey="Gronberg H" first="Henrik" last="Grönberg">Henrik Grönberg</name><affiliation><nlm:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation></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><nlm:affiliation>Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.</nlm:affiliation></affiliation></author><author><name sortKey="Schleutker, Johanna" sort="Schleutker, Johanna" uniqKey="Schleutker J" first="Johanna" last="Schleutker">Johanna Schleutker</name><affiliation><nlm:affiliation>Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.</nlm:affiliation></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><nlm:affiliation>Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev, DK, 2730, Denmark.</nlm:affiliation></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><nlm:affiliation>Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Pashayan, Nora" sort="Pashayan, Nora" uniqKey="Pashayan N" first="Nora" last="Pashayan">Nora Pashayan</name><affiliation><nlm:affiliation>Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom.</nlm:affiliation></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><nlm:affiliation>Forvie Site, Cambridge Institute of Public Health, University of Cambridge, Robinson Way, Cambridge, CB2 0SR, United Kingdom.</nlm:affiliation></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><nlm:affiliation>Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.</nlm:affiliation></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><nlm:affiliation>International Epidemiology Institute, 1455 Research Blvd, Suite 550, Rockville, Maryland.</nlm:affiliation></affiliation></author><author><name sortKey="Thibodeau, Stephen" sort="Thibodeau, Stephen" uniqKey="Thibodeau S" first="Stephen" last="Thibodeau">Stephen Thibodeau</name><affiliation><nlm:affiliation>Mayo Clinic, Rochester, Minnesota.</nlm:affiliation></affiliation></author><author><name sortKey="Maier, Christiane" sort="Maier, Christiane" uniqKey="Maier C" first="Christiane" last="Maier">Christiane Maier</name><affiliation><nlm:affiliation>Department of Urology, University Hospital Ulm, Germany.</nlm:affiliation></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></affiliation></author><author><name sortKey="Cybulski, Cezary" sort="Cybulski, Cezary" uniqKey="Cybulski C" first="Cezary" last="Cybulski">Cezary Cybulski</name><affiliation><nlm:affiliation>International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.</nlm:affiliation></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><nlm:affiliation>Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah.</nlm:affiliation></affiliation></author><author><name sortKey="Brenner, Hermann" sort="Brenner, Hermann" uniqKey="Brenner H" first="Hermann" last="Brenner">Hermann Brenner</name><affiliation><nlm:affiliation>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Park, Jong" sort="Park, Jong" uniqKey="Park J" first="Jong" last="Park">Jong Park</name><affiliation><nlm:affiliation>Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr, Tampa, Florida.</nlm:affiliation></affiliation></author><author><name sortKey="Kaneva, Radka" sort="Kaneva, Radka" uniqKey="Kaneva R" first="Radka" last="Kaneva">Radka Kaneva</name><affiliation><nlm:affiliation>Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University - Sofia, 2 Zdrave St, Sofia, 1431, Bulgaria.</nlm:affiliation></affiliation></author><author><name sortKey="Batra, Jyotsna" sort="Batra, Jyotsna" uniqKey="Batra J" first="Jyotsna" last="Batra">Jyotsna Batra</name><affiliation><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></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><nlm:affiliation>Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.</nlm:affiliation></affiliation></author><author><name sortKey="Pandha, Hardev" sort="Pandha, Hardev" uniqKey="Pandha H" first="Hardev" last="Pandha">Hardev Pandha</name><affiliation><nlm:affiliation>The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Lathrop, Mark" sort="Lathrop, Mark" uniqKey="Lathrop M" first="Mark" last="Lathrop">Mark Lathrop</name><affiliation><nlm:affiliation>Commissariat à L'Energie Atomique, Center National De Génotypage, Evry, France.</nlm:affiliation></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><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation></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><nlm:affiliation>NIHR Bristol Biomedical Research Unit in Nutrition, Bristol, United Kingdom.</nlm:affiliation></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></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><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation></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><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation></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><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation></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><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation></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><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Gunnell, David" sort="Gunnell, David" uniqKey="Gunnell D" first="David" last="Gunnell">David Gunnell</name><affiliation><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Palmer, Tom" sort="Palmer, Tom" uniqKey="Palmer T" first="Tom" last="Palmer">Tom Palmer</name><affiliation><nlm:affiliation>Department of Mathematics and Statistics, Lancaster University, Lancaster, United Kingdom.</nlm:affiliation></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><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation></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><nlm:affiliation>Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom.</nlm:affiliation></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><nlm:affiliation>Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Eeles, Rosalind" sort="Eeles, Rosalind" uniqKey="Eeles R" first="Rosalind" last="Eeles">Rosalind Eeles</name><affiliation><nlm:affiliation>The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Easton, Doug" sort="Easton, Doug" uniqKey="Easton D" first="Doug" last="Easton">Doug Easton</name><affiliation><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></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:affiliation>The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, United Kingdom.</nlm:affiliation></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><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></affiliation></author><author><name sortKey="Benlloch, Sara" sort="Benlloch, Sara" uniqKey="Benlloch S" first="Sara" last="Benlloch">Sara Benlloch</name><affiliation><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></affiliation></author><author><name sortKey="Muir, Kenneth" sort="Muir, Kenneth" uniqKey="Muir K" first="Kenneth" last="Muir">Kenneth Muir</name><affiliation><nlm:affiliation>University of Warwick, Coventry, United Kingdom.</nlm:affiliation></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:affiliation>The Cancer Council Victoria, 615 St. Kilda Road, Melbourne, Victoria, 3004, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Wiklund, Fredrik" sort="Wiklund, Fredrik" uniqKey="Wiklund F" first="Fredrik" last="Wiklund">Fredrik Wiklund</name><affiliation><nlm:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Gronberg, Henrik" sort="Gronberg, Henrik" uniqKey="Gronberg H" first="Henrik" last="Grönberg">Henrik Grönberg</name><affiliation><nlm:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation></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><nlm:affiliation>Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.</nlm:affiliation></affiliation></author><author><name sortKey="Schleutker, Johanna" sort="Schleutker, Johanna" uniqKey="Schleutker J" first="Johanna" last="Schleutker">Johanna Schleutker</name><affiliation><nlm:affiliation>Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.</nlm:affiliation></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><nlm:affiliation>Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev, DK, 2730, Denmark.</nlm:affiliation></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><nlm:affiliation>Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Pashayan, Nora" sort="Pashayan, Nora" uniqKey="Pashayan N" first="Nora" last="Pashayan">Nora Pashayan</name><affiliation><nlm:affiliation>Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom.</nlm:affiliation></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><nlm:affiliation>Forvie Site, Cambridge Institute of Public Health, University of Cambridge, Robinson Way, Cambridge, CB2 0SR, United Kingdom.</nlm:affiliation></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><nlm:affiliation>Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.</nlm:affiliation></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><nlm:affiliation>International Epidemiology Institute, 1455 Research Blvd, Suite 550, Rockville, Maryland.</nlm:affiliation></affiliation></author><author><name sortKey="Thibodeau, Stephen" sort="Thibodeau, Stephen" uniqKey="Thibodeau S" first="Stephen" last="Thibodeau">Stephen Thibodeau</name><affiliation><nlm:affiliation>Mayo Clinic, Rochester, Minnesota.</nlm:affiliation></affiliation></author><author><name sortKey="Maier, Christiane" sort="Maier, Christiane" uniqKey="Maier C" first="Christiane" last="Maier">Christiane Maier</name><affiliation><nlm:affiliation>Department of Urology, University Hospital Ulm, Germany.</nlm:affiliation></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></affiliation></author><author><name sortKey="Cybulski, Cezary" sort="Cybulski, Cezary" uniqKey="Cybulski C" first="Cezary" last="Cybulski">Cezary Cybulski</name><affiliation><nlm:affiliation>International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.</nlm:affiliation></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><nlm:affiliation>Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah.</nlm:affiliation></affiliation></author><author><name sortKey="Brenner, Hermann" sort="Brenner, Hermann" uniqKey="Brenner H" first="Hermann" last="Brenner">Hermann Brenner</name><affiliation><nlm:affiliation>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Park, Jong" sort="Park, Jong" uniqKey="Park J" first="Jong" last="Park">Jong Park</name><affiliation><nlm:affiliation>Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr, Tampa, Florida.</nlm:affiliation></affiliation></author><author><name sortKey="Kaneva, Radka" sort="Kaneva, Radka" uniqKey="Kaneva R" first="Radka" last="Kaneva">Radka Kaneva</name><affiliation><nlm:affiliation>Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University - Sofia, 2 Zdrave St, Sofia, 1431, Bulgaria.</nlm:affiliation></affiliation></author><author><name sortKey="Batra, Jyotsna" sort="Batra, Jyotsna" uniqKey="Batra J" first="Jyotsna" last="Batra">Jyotsna Batra</name><affiliation><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></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><nlm:affiliation>Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.</nlm:affiliation></affiliation></author><author><name sortKey="Pandha, Hardev" sort="Pandha, Hardev" uniqKey="Pandha H" first="Hardev" last="Pandha">Hardev Pandha</name><affiliation><nlm:affiliation>The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Lathrop, Mark" sort="Lathrop, Mark" uniqKey="Lathrop M" first="Mark" last="Lathrop">Mark Lathrop</name><affiliation><nlm:affiliation>Commissariat à L'Energie Atomique, Center National De Génotypage, Evry, France.</nlm:affiliation></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><nlm:affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</nlm:affiliation></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><nlm:affiliation>NIHR Bristol Biomedical Research Unit in Nutrition, Bristol, United Kingdom.</nlm:affiliation></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="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="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="methods" xml:lang="en"><term>Mendelian Randomization Analysis</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Prostatic Neoplasms</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></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><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27225428</PMID><DateCreated><Year>2016</Year><Month>07</Month><Day>15</Day></DateCreated><DateCompleted><Year>2017</Year><Month>06</Month><Day>23</Day></DateCompleted><DateRevised><Year>2017</Year><Month>09</Month><Day>22</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1097-0215</ISSN><JournalIssue CitedMedium="Internet"><Volume>139</Volume><Issue>7</Issue><PubDate><Year>2016</Year><Month>Oct</Month><Day>01</Day></PubDate></JournalIssue><Title>International journal of cancer</Title><ISOAbbreviation>Int. J. Cancer</ISOAbbreviation></Journal><ArticleTitle>Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels.</ArticleTitle><Pagination><MedlinePgn>1520-33</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/ijc.30206</ELocationID><Abstract><AbstractText>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.</AbstractText><CopyrightInformation>© 2016 UICC.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bonilla</LastName><ForeName>Carolina</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>MRC/University of Bristol Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lewis</LastName><ForeName>Sarah J</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>MRC/University of Bristol Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rowlands</LastName><ForeName>Mari-Anne</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gaunt</LastName><ForeName>Tom R</ForeName><Initials>TR</Initials><AffiliationInfo><Affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>MRC/University of Bristol Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Davey Smith</LastName><ForeName>George</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>MRC/University of Bristol Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gunnell</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Palmer</LastName><ForeName>Tom</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Mathematics and Statistics, Lancaster University, Lancaster, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Donovan</LastName><ForeName>Jenny L</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hamdy</LastName><ForeName>Freddie C</ForeName><Initials>FC</Initials><AffiliationInfo><Affiliation>Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Neal</LastName><ForeName>David E</ForeName><Initials>DE</Initials><AffiliationInfo><Affiliation>Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Surgical Oncology (Uro-Oncology: S4), University of Cambridge, Box 279, Addenbrooke's Hospital, Hills Road, Cambridge, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Eeles</LastName><ForeName>Rosalind</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Royal Marsden NHS Foundation Trust, Fulham and Sutton, London and Surrey, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Easton</LastName><ForeName>Doug</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kote-Jarai</LastName><ForeName>Zsofia</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Al Olama</LastName><ForeName>Ali Amin</ForeName><Initials>AA</Initials><AffiliationInfo><Affiliation>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Benlloch</LastName><ForeName>Sara</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Muir</LastName><ForeName>Kenneth</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>University of Warwick, Coventry, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Population Health, University of Manchester, Manchester, M13 9PL, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Giles</LastName><ForeName>Graham G</ForeName><Initials>GG</Initials><AffiliationInfo><Affiliation>The Cancer Council Victoria, 615 St. Kilda Road, Melbourne, Victoria, 3004, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Victoria, 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wiklund</LastName><ForeName>Fredrik</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Grönberg</LastName><ForeName>Henrik</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Haiman</LastName><ForeName>Christopher A</ForeName><Initials>CA</Initials><AffiliationInfo><Affiliation>Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schleutker</LastName><ForeName>Johanna</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Biomedical Technology/BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nordestgaard</LastName><ForeName>Børge G</ForeName><Initials>BG</Initials><AffiliationInfo><Affiliation>Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev, DK, 2730, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Travis</LastName><ForeName>Ruth C</ForeName><Initials>RC</Initials><AffiliationInfo><Affiliation>Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pashayan</LastName><ForeName>Nora</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Applied Health Research, University College London, 1-19 Torrington Place, London, WC1E 7HB, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Khaw</LastName><ForeName>Kay-Tee</ForeName><Initials>KT</Initials><AffiliationInfo><Affiliation>Forvie Site, Cambridge Institute of Public Health, University of Cambridge, Robinson Way, Cambridge, CB2 0SR, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stanford</LastName><ForeName>Janet L</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Blot</LastName><ForeName>William J</ForeName><Initials>WJ</Initials><AffiliationInfo><Affiliation>International Epidemiology Institute, 1455 Research Blvd, Suite 550, Rockville, Maryland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thibodeau</LastName><ForeName>Stephen</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Mayo Clinic, Rochester, Minnesota.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maier</LastName><ForeName>Christiane</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Urology, University Hospital Ulm, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Human Genetics, University Hospital Ulm, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kibel</LastName><ForeName>Adam S</ForeName><Initials>AS</Initials><AffiliationInfo><Affiliation>Brigham and Women's Hospital/Dana-Farber Cancer Institute, 45 Francis Street-ASB II-3, Boston, Massachussets.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Washington University, St Louis, Missouri.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cybulski</LastName><ForeName>Cezary</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cannon-Albright</LastName><ForeName>Lisa</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brenner</LastName><ForeName>Hermann</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Park</LastName><ForeName>Jong</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr, Tampa, Florida.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kaneva</LastName><ForeName>Radka</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University - Sofia, 2 Zdrave St, Sofia, 1431, Bulgaria.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Batra</LastName><ForeName>Jyotsna</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Teixeira</LastName><ForeName>Manuel R</ForeName><Initials>MR</Initials><AffiliationInfo><Affiliation>Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pandha</LastName><ForeName>Hardev</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>PRACTICAL consortium</CollectiveName></Author><Author ValidYN="Y"><LastName>Lathrop</LastName><ForeName>Mark</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Commissariat à L'Energie Atomique, Center National De Génotypage, Evry, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>McGill University-Génome Québec Innovation Centre, Montreal, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Martin</LastName><ForeName>Richard M</ForeName><Initials>RM</Initials><AffiliationInfo><Affiliation>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>MRC/University of Bristol Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>NIHR Bristol Biomedical Research Unit in Nutrition, Bristol, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Holly</LastName><ForeName>Jeff M P</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>NIHR Bristol Biomedical Research Unit in Nutrition, Bristol, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>IGFs and Metabolic Endocrinology Group, School of Clinical Sciences North Bristol, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>G0600705</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>R01 CA092447</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>102215</GrantID><Agency>Wellcome Trust</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>MC_PC_15018</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>14136</GrantID><Agency>Cancer Research UK</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>G0401527</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>MC_UU_12013/1</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>A19169</GrantID><Agency>Cancer Research UK</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>MC_UU_12013/8</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>06</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Int J Cancer</MedlineTA><NlmUniqueID>0042124</NlmUniqueID><ISSNLinking>0020-7136</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018969">Insulin-Like Growth Factor Binding Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D013002">Somatomedins</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Int J Epidemiol. 2013 Feb;42(1):111-27</RefSource><PMID Version="1">22507743</PMID></CommentsCorrections><CommentsCorrections 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MajorTopicYN="N">prostate cancer</Keyword><Keyword MajorTopicYN="N">single nucleotide polymorphisms</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>11</Month><Day>24</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2016</Year><Month>04</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>04</Month><Day>07</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>5</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>5</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>6</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27225428</ArticleId><ArticleId 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