Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts
AbstractObjectivesTo develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age.DesignAnalysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. The...
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| creator | Seibert, Tyler M Fan, Chun Chieh Wang, Yunpeng Zuber, Verena Karunamuni, Roshan Parsons, J Kellogg Eeles, Rosalind A Easton, Douglas F Kote-Jarai, ZSofia Al Olama, Ali Amin Garcia, Sara Benlloch Muir, Kenneth Grönberg, Henrik Wiklund, Fredrik Aly, Markus Schleutker, Johanna Sipeky, Csilla Tammela, Teuvo LJ Nordestgaard, Børge G Nielsen, Sune F Weischer, Maren Bisbjerg, Rasmus Røder, M Andreas Iversen, Peter Key, Tim J Travis, Ruth C Neal, David E Donovan, Jenny L Hamdy, Freddie C Pharoah, Paul Pashayan, Nora Khaw, Kay-Tee Maier, Christiane Vogel, Walther Luedeke, Manuel Herkommer, Kathleen Kibel, Adam S Cybulski, Cezary Wokolorczyk, Dominika Kluzniak, Wojciech Cannon-Albright, Lisa Brenner, Hermann Cuk, Katarina Saum, Kai-Uwe Park, Jong Y Sellers, Thomas A Slavov, Chavdar Kaneva, Radka Mitev, Vanio Batra, Jyotsna Clements, Judith A Spurdle, Amanda Teixeira, Manuel R Paulo, Paula Maia, Sofia Pandha, Hardev Michael, Agnieszka Kierzek, Andrzej Karow, David S Mills, Ian G Andreassen, Ole A Dale, Anders M |
| description | AbstractObjectivesTo develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age.DesignAnalysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa.SettingMultiple institutions that were members of international PRACTICAL consortium.ParticipantsAll consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men.Main outcome measuresPrediction with hazard score of age of onset of aggressive cancer in validation set.ResultsIn the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score.ConclusionsPolygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa. |
| doi_str_mv | 10.1136/bmj.j5757 |
| format | Article |
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These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa.SettingMultiple institutions that were members of international PRACTICAL consortium.ParticipantsAll consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men.Main outcome measuresPrediction with hazard score of age of onset of aggressive cancer in validation set.ResultsIn the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P<10−16). When men in the validation set with high scores (>98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score.ConclusionsPolygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa.</description><identifier>ISSN: 0959-8138</identifier><identifier>ISSN: 0959-535X</identifier><identifier>EISSN: 1756-1833</identifier><identifier>DOI: 10.1136/bmj.j5757</identifier><identifier>PMID: 29321194</identifier><language>eng</language><publisher>England: BMJ Publishing Group LTD</publisher><subject>Age ; Age of Onset ; Aged ; Antigens ; Cohort Studies ; Consortia ; Diagnosis ; Disease-Free Survival ; Early Detection of Cancer - methods ; Genotype ; Genotypes ; Health risk assessment ; Humans ; Kallikreins - analysis ; Male ; Medical screening ; Metastases ; Metastasis ; Middle Aged ; Mortality ; Outcome Assessment, Health Care ; Polymorphism, Single Nucleotide - genetics ; Predictive Value of Tests ; Prostate cancer ; Prostate-Specific Antigen - analysis ; Prostatic Neoplasms - blood ; Prostatic Neoplasms - diagnosis ; Prostatic Neoplasms - genetics ; Risk Assessment ; Single-nucleotide polymorphism ; Survival ; Survival Analysis ; Tumors ; White People - genetics</subject><ispartof>BMJ (Online), 2018-01, Vol.360, p.j5757-j5757</ispartof><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to</rights><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</rights><rights>Copyright: 2018 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to 2018 BMJ</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b536t-7e90e5128d3d096575e0d97d1c60e4f4e15d500e4a89c7999f73854d0edeb6f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,551,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29321194$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:137425038$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Seibert, Tyler M</creatorcontrib><creatorcontrib>Fan, Chun Chieh</creatorcontrib><creatorcontrib>Wang, Yunpeng</creatorcontrib><creatorcontrib>Zuber, Verena</creatorcontrib><creatorcontrib>Karunamuni, Roshan</creatorcontrib><creatorcontrib>Parsons, J Kellogg</creatorcontrib><creatorcontrib>Eeles, Rosalind A</creatorcontrib><creatorcontrib>Easton, Douglas F</creatorcontrib><creatorcontrib>Kote-Jarai, ZSofia</creatorcontrib><creatorcontrib>Al Olama, Ali Amin</creatorcontrib><creatorcontrib>Garcia, Sara Benlloch</creatorcontrib><creatorcontrib>Muir, Kenneth</creatorcontrib><creatorcontrib>Grönberg, Henrik</creatorcontrib><creatorcontrib>Wiklund, Fredrik</creatorcontrib><creatorcontrib>Aly, Markus</creatorcontrib><creatorcontrib>Schleutker, Johanna</creatorcontrib><creatorcontrib>Sipeky, Csilla</creatorcontrib><creatorcontrib>Tammela, Teuvo LJ</creatorcontrib><creatorcontrib>Nordestgaard, Børge G</creatorcontrib><creatorcontrib>Nielsen, Sune F</creatorcontrib><creatorcontrib>Weischer, Maren</creatorcontrib><creatorcontrib>Bisbjerg, Rasmus</creatorcontrib><creatorcontrib>Røder, M Andreas</creatorcontrib><creatorcontrib>Iversen, Peter</creatorcontrib><creatorcontrib>Key, Tim J</creatorcontrib><creatorcontrib>Travis, Ruth C</creatorcontrib><creatorcontrib>Neal, David E</creatorcontrib><creatorcontrib>Donovan, Jenny L</creatorcontrib><creatorcontrib>Hamdy, Freddie C</creatorcontrib><creatorcontrib>Pharoah, Paul</creatorcontrib><creatorcontrib>Pashayan, Nora</creatorcontrib><creatorcontrib>Khaw, Kay-Tee</creatorcontrib><creatorcontrib>Maier, Christiane</creatorcontrib><creatorcontrib>Vogel, Walther</creatorcontrib><creatorcontrib>Luedeke, Manuel</creatorcontrib><creatorcontrib>Herkommer, Kathleen</creatorcontrib><creatorcontrib>Kibel, Adam S</creatorcontrib><creatorcontrib>Cybulski, Cezary</creatorcontrib><creatorcontrib>Wokolorczyk, Dominika</creatorcontrib><creatorcontrib>Kluzniak, Wojciech</creatorcontrib><creatorcontrib>Cannon-Albright, Lisa</creatorcontrib><creatorcontrib>Brenner, Hermann</creatorcontrib><creatorcontrib>Cuk, Katarina</creatorcontrib><creatorcontrib>Saum, Kai-Uwe</creatorcontrib><creatorcontrib>Park, Jong Y</creatorcontrib><creatorcontrib>Sellers, Thomas A</creatorcontrib><creatorcontrib>Slavov, Chavdar</creatorcontrib><creatorcontrib>Kaneva, Radka</creatorcontrib><creatorcontrib>Mitev, Vanio</creatorcontrib><creatorcontrib>Batra, Jyotsna</creatorcontrib><creatorcontrib>Clements, Judith A</creatorcontrib><creatorcontrib>Spurdle, Amanda</creatorcontrib><creatorcontrib>Teixeira, Manuel R</creatorcontrib><creatorcontrib>Paulo, Paula</creatorcontrib><creatorcontrib>Maia, Sofia</creatorcontrib><creatorcontrib>Pandha, Hardev</creatorcontrib><creatorcontrib>Michael, Agnieszka</creatorcontrib><creatorcontrib>Kierzek, Andrzej</creatorcontrib><creatorcontrib>Karow, David S</creatorcontrib><creatorcontrib>Mills, Ian G</creatorcontrib><creatorcontrib>Andreassen, Ole A</creatorcontrib><creatorcontrib>Dale, Anders M</creatorcontrib><creatorcontrib>PRACTICAL Consortium</creatorcontrib><creatorcontrib>The PRACTICAL Consortium</creatorcontrib><title>Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts</title><title>BMJ (Online)</title><addtitle>BMJ</addtitle><description>AbstractObjectivesTo develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age.DesignAnalysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa.SettingMultiple institutions that were members of international PRACTICAL consortium.ParticipantsAll consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men.Main outcome measuresPrediction with hazard score of age of onset of aggressive cancer in validation set.ResultsIn the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P<10−16). When men in the validation set with high scores (>98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score.ConclusionsPolygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa.</description><subject>Age</subject><subject>Age of Onset</subject><subject>Aged</subject><subject>Antigens</subject><subject>Cohort Studies</subject><subject>Consortia</subject><subject>Diagnosis</subject><subject>Disease-Free Survival</subject><subject>Early Detection of Cancer - methods</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Health risk assessment</subject><subject>Humans</subject><subject>Kallikreins - analysis</subject><subject>Male</subject><subject>Medical screening</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Outcome Assessment, Health Care</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Predictive Value of Tests</subject><subject>Prostate cancer</subject><subject>Prostate-Specific Antigen - analysis</subject><subject>Prostatic Neoplasms - blood</subject><subject>Prostatic Neoplasms - diagnosis</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Risk Assessment</subject><subject>Single-nucleotide polymorphism</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>Tumors</subject><subject>White People - 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Andrzej</creator><creator>Karow, David S</creator><creator>Mills, Ian G</creator><creator>Andreassen, Ole A</creator><creator>Dale, Anders M</creator><general>BMJ Publishing Group LTD</general><general>BMJ Publishing Group Ltd</general><scope>9YT</scope><scope>ACMMV</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ASE</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FPQ</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K6X</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20180110</creationdate><title>Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts</title><author>Seibert, Tyler M ; Fan, Chun Chieh ; Wang, Yunpeng ; Zuber, Verena ; Karunamuni, Roshan ; Parsons, J Kellogg ; Eeles, Rosalind A ; Easton, Douglas F ; Kote-Jarai, ZSofia ; Al Olama, Ali Amin ; Garcia, Sara Benlloch ; Muir, Kenneth ; Grönberg, Henrik ; Wiklund, Fredrik ; Aly, Markus ; Schleutker, Johanna ; Sipeky, Csilla ; Tammela, Teuvo LJ ; Nordestgaard, Børge G ; Nielsen, Sune F ; Weischer, Maren ; Bisbjerg, Rasmus ; Røder, M Andreas ; Iversen, Peter ; Key, Tim J ; Travis, Ruth C ; Neal, David E ; Donovan, Jenny L ; Hamdy, Freddie C ; Pharoah, Paul ; Pashayan, Nora ; Khaw, Kay-Tee ; Maier, Christiane ; Vogel, Walther ; Luedeke, Manuel ; Herkommer, Kathleen ; Kibel, Adam S ; Cybulski, Cezary ; Wokolorczyk, Dominika ; Kluzniak, Wojciech ; Cannon-Albright, Lisa ; Brenner, Hermann ; Cuk, Katarina ; Saum, Kai-Uwe ; Park, Jong Y ; Sellers, Thomas A ; Slavov, Chavdar ; Kaneva, Radka ; Mitev, Vanio ; Batra, Jyotsna ; Clements, Judith A ; Spurdle, Amanda ; Teixeira, Manuel R ; Paulo, Paula ; Maia, Sofia ; Pandha, Hardev ; Michael, Agnieszka ; Kierzek, Andrzej ; Karow, David S ; Mills, Ian G ; Andreassen, Ole A ; Dale, Anders M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b536t-7e90e5128d3d096575e0d97d1c60e4f4e15d500e4a89c7999f73854d0edeb6f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Age</topic><topic>Age of Onset</topic><topic>Aged</topic><topic>Antigens</topic><topic>Cohort Studies</topic><topic>Consortia</topic><topic>Diagnosis</topic><topic>Disease-Free Survival</topic><topic>Early Detection of Cancer - methods</topic><topic>Genotype</topic><topic>Genotypes</topic><topic>Health risk assessment</topic><topic>Humans</topic><topic>Kallikreins - analysis</topic><topic>Male</topic><topic>Medical screening</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Outcome Assessment, Health Care</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Predictive Value of Tests</topic><topic>Prostate cancer</topic><topic>Prostate-Specific Antigen - analysis</topic><topic>Prostatic Neoplasms - blood</topic><topic>Prostatic Neoplasms - diagnosis</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Risk Assessment</topic><topic>Single-nucleotide polymorphism</topic><topic>Survival</topic><topic>Survival Analysis</topic><topic>Tumors</topic><topic>White People - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Seibert, Tyler M</creatorcontrib><creatorcontrib>Fan, Chun Chieh</creatorcontrib><creatorcontrib>Wang, Yunpeng</creatorcontrib><creatorcontrib>Zuber, Verena</creatorcontrib><creatorcontrib>Karunamuni, Roshan</creatorcontrib><creatorcontrib>Parsons, J Kellogg</creatorcontrib><creatorcontrib>Eeles, Rosalind A</creatorcontrib><creatorcontrib>Easton, Douglas F</creatorcontrib><creatorcontrib>Kote-Jarai, ZSofia</creatorcontrib><creatorcontrib>Al Olama, Ali Amin</creatorcontrib><creatorcontrib>Garcia, Sara Benlloch</creatorcontrib><creatorcontrib>Muir, Kenneth</creatorcontrib><creatorcontrib>Grönberg, Henrik</creatorcontrib><creatorcontrib>Wiklund, Fredrik</creatorcontrib><creatorcontrib>Aly, Markus</creatorcontrib><creatorcontrib>Schleutker, Johanna</creatorcontrib><creatorcontrib>Sipeky, Csilla</creatorcontrib><creatorcontrib>Tammela, Teuvo LJ</creatorcontrib><creatorcontrib>Nordestgaard, Børge G</creatorcontrib><creatorcontrib>Nielsen, Sune F</creatorcontrib><creatorcontrib>Weischer, Maren</creatorcontrib><creatorcontrib>Bisbjerg, Rasmus</creatorcontrib><creatorcontrib>Røder, M Andreas</creatorcontrib><creatorcontrib>Iversen, Peter</creatorcontrib><creatorcontrib>Key, Tim J</creatorcontrib><creatorcontrib>Travis, Ruth C</creatorcontrib><creatorcontrib>Neal, David E</creatorcontrib><creatorcontrib>Donovan, Jenny L</creatorcontrib><creatorcontrib>Hamdy, Freddie C</creatorcontrib><creatorcontrib>Pharoah, Paul</creatorcontrib><creatorcontrib>Pashayan, Nora</creatorcontrib><creatorcontrib>Khaw, Kay-Tee</creatorcontrib><creatorcontrib>Maier, Christiane</creatorcontrib><creatorcontrib>Vogel, Walther</creatorcontrib><creatorcontrib>Luedeke, Manuel</creatorcontrib><creatorcontrib>Herkommer, Kathleen</creatorcontrib><creatorcontrib>Kibel, Adam S</creatorcontrib><creatorcontrib>Cybulski, Cezary</creatorcontrib><creatorcontrib>Wokolorczyk, Dominika</creatorcontrib><creatorcontrib>Kluzniak, Wojciech</creatorcontrib><creatorcontrib>Cannon-Albright, Lisa</creatorcontrib><creatorcontrib>Brenner, Hermann</creatorcontrib><creatorcontrib>Cuk, Katarina</creatorcontrib><creatorcontrib>Saum, Kai-Uwe</creatorcontrib><creatorcontrib>Park, Jong Y</creatorcontrib><creatorcontrib>Sellers, Thomas A</creatorcontrib><creatorcontrib>Slavov, Chavdar</creatorcontrib><creatorcontrib>Kaneva, Radka</creatorcontrib><creatorcontrib>Mitev, Vanio</creatorcontrib><creatorcontrib>Batra, Jyotsna</creatorcontrib><creatorcontrib>Clements, Judith A</creatorcontrib><creatorcontrib>Spurdle, Amanda</creatorcontrib><creatorcontrib>Teixeira, Manuel R</creatorcontrib><creatorcontrib>Paulo, Paula</creatorcontrib><creatorcontrib>Maia, Sofia</creatorcontrib><creatorcontrib>Pandha, Hardev</creatorcontrib><creatorcontrib>Michael, Agnieszka</creatorcontrib><creatorcontrib>Kierzek, Andrzej</creatorcontrib><creatorcontrib>Karow, David S</creatorcontrib><creatorcontrib>Mills, Ian G</creatorcontrib><creatorcontrib>Andreassen, Ole A</creatorcontrib><creatorcontrib>Dale, Anders M</creatorcontrib><creatorcontrib>PRACTICAL Consortium</creatorcontrib><creatorcontrib>The PRACTICAL Consortium</creatorcontrib><collection>BMJ Open Access Journals</collection><collection>BMJ Journals:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Index</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>British Nursing Index (BNI) (1985 to Present)</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>British Nursing Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>BMJ (Online)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Seibert, Tyler M</au><au>Fan, Chun Chieh</au><au>Wang, Yunpeng</au><au>Zuber, Verena</au><au>Karunamuni, Roshan</au><au>Parsons, J Kellogg</au><au>Eeles, Rosalind A</au><au>Easton, Douglas F</au><au>Kote-Jarai, ZSofia</au><au>Al Olama, Ali Amin</au><au>Garcia, Sara Benlloch</au><au>Muir, Kenneth</au><au>Grönberg, Henrik</au><au>Wiklund, Fredrik</au><au>Aly, Markus</au><au>Schleutker, Johanna</au><au>Sipeky, Csilla</au><au>Tammela, Teuvo LJ</au><au>Nordestgaard, Børge G</au><au>Nielsen, Sune F</au><au>Weischer, Maren</au><au>Bisbjerg, Rasmus</au><au>Røder, M Andreas</au><au>Iversen, Peter</au><au>Key, Tim J</au><au>Travis, Ruth C</au><au>Neal, David E</au><au>Donovan, Jenny L</au><au>Hamdy, Freddie C</au><au>Pharoah, Paul</au><au>Pashayan, Nora</au><au>Khaw, Kay-Tee</au><au>Maier, Christiane</au><au>Vogel, Walther</au><au>Luedeke, Manuel</au><au>Herkommer, Kathleen</au><au>Kibel, Adam S</au><au>Cybulski, Cezary</au><au>Wokolorczyk, Dominika</au><au>Kluzniak, Wojciech</au><au>Cannon-Albright, Lisa</au><au>Brenner, Hermann</au><au>Cuk, Katarina</au><au>Saum, Kai-Uwe</au><au>Park, Jong Y</au><au>Sellers, Thomas A</au><au>Slavov, Chavdar</au><au>Kaneva, Radka</au><au>Mitev, Vanio</au><au>Batra, Jyotsna</au><au>Clements, Judith A</au><au>Spurdle, Amanda</au><au>Teixeira, Manuel R</au><au>Paulo, Paula</au><au>Maia, Sofia</au><au>Pandha, Hardev</au><au>Michael, Agnieszka</au><au>Kierzek, Andrzej</au><au>Karow, David S</au><au>Mills, Ian G</au><au>Andreassen, Ole A</au><au>Dale, Anders M</au><aucorp>PRACTICAL Consortium</aucorp><aucorp>The PRACTICAL Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts</atitle><jtitle>BMJ (Online)</jtitle><addtitle>BMJ</addtitle><date>2018-01-10</date><risdate>2018</risdate><volume>360</volume><spage>j5757</spage><epage>j5757</epage><pages>j5757-j5757</pages><issn>0959-8138</issn><issn>0959-535X</issn><eissn>1756-1833</eissn><abstract>AbstractObjectivesTo develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age.DesignAnalysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa.SettingMultiple institutions that were members of international PRACTICAL consortium.ParticipantsAll consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men.Main outcome measuresPrediction with hazard score of age of onset of aggressive cancer in validation set.ResultsIn the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P<10−16). When men in the validation set with high scores (>98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score.ConclusionsPolygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa.</abstract><cop>England</cop><pub>BMJ Publishing Group LTD</pub><pmid>29321194</pmid><doi>10.1136/bmj.j5757</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0959-8138 |
| ispartof | BMJ (Online), 2018-01, Vol.360, p.j5757-j5757 |
| issn | 0959-8138 0959-535X 1756-1833 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_491330 |
| source | MEDLINE; SWEPUB Freely available online; Jstor Complete Legacy |
| subjects | Age Age of Onset Aged Antigens Cohort Studies Consortia Diagnosis Disease-Free Survival Early Detection of Cancer - methods Genotype Genotypes Health risk assessment Humans Kallikreins - analysis Male Medical screening Metastases Metastasis Middle Aged Mortality Outcome Assessment, Health Care Polymorphism, Single Nucleotide - genetics Predictive Value of Tests Prostate cancer Prostate-Specific Antigen - analysis Prostatic Neoplasms - blood Prostatic Neoplasms - diagnosis Prostatic Neoplasms - genetics Risk Assessment Single-nucleotide polymorphism Survival Survival Analysis Tumors White People - genetics |
| title | Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts |
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