Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants
Purpose We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks forBRCA1andBRCA2pathogenic variant carriers. Methods Retrospective cohort data on 18,935BRCA1and 12,339BRCA2female pathogenic variant carrier...
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| creator | Barnes, Daniel R McGuffog, Lesley Mooij, Thea M Dennis, Joe Adlard, Julian Ahmed, Munaza Andrieu, Nadine Andrulis, Irene L Arun, Banu K Azzollini, Jacopo Balmaña, Judith Benitez, Javier Berthet, Pascaline Blanco, Amie M Blok, Marinus J Bradbury, Angela R Brennan, Paul Buys, Saundra S Caligo, Maria A Campbell, Ian Colas, Chrystelle Cook, Jackie Davidson, Rosemarie de Putter, Robin Delnatte, Capucine Devilee, Peter Ding, Yuan Chun Domchek, Susan M Ejlertsen, Bent Engel, Christoph Faivre, Laurence Friedman, Eitan Frost, Debra Gerdes, Anne-Marie Gesta, Paul Glendon, Gord Godwin, Andrew K Goldgar, David E Hamann, Ute Hogervorst, Frans B. L Horvath, Judit Hulick, Peter J Imyanitov, Evgeny N Isaacs, Claudine Izatt, Louise Izquierdo, Angel Jakubowska, Anna Janavicius, Ramunas Koudijs, Marco Kruse, Torben A Laitman, Yael Lazaro, Conxi Lesueur, Fabienne Loud, Jennifer T Lubiński, Jan Mebirouk, Noura Mensenkamp, Arjen R Montagna, Marco Mouret-Fourme, Emmanuelle Nathanson, Katherine L Osorio, Ana Ott, Claus-Eric Papi, Laura Park, Sue K Parsons, Michael T Peissel, Bernard Peterlongo, Paolo Pfeiler, Georg Prajzendanc, Karolina Radice, Paolo Ramser, Juliane Rantala, Johanna Rennert, Gad Risch, Harvey A Salani, Ritu Schuster, Hélène Shah, Payal D Sharma, Priyanka Singer, Christian F Slavin, Thomas P Spurdle, Amanda B Steinsnyder, Zoe Stoppa-Lyonnet, Dominique Tan, Yen Yen Teixeira, Manuel R Teo, Soo Hwang Thull, Darcy L Tognazzo, Silvia Toland, Amanda E Trainer, Alison H Tung, Nadine van Rensburg, Elizabeth J Wagner, Gabriel Yadav, Siddhartha Yannoukakos, Drakoulis Offit, Kenneth Thomassen, Mads Couch, Fergus J Schmutzler, Rita K Antoniou, Antonis C |
| description | Purpose We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks forBRCA1andBRCA2pathogenic variant carriers. Methods Retrospective cohort data on 18,935BRCA1and 12,339BRCA2female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results The ER-negative PRS showed the strongest association with BC risk forBRCA1carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33],P = 3x10(-72)). ForBRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36],P = 7x10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk forBRCA1(HR = 1.32 [95% CI 1.25-1.40],P = 3x10(-22)) andBRCA2(HR = 1.44 [95% CI 1.30-1.60],P = 4x10(-12)) carriers. The associations in the prospective cohort were similar. Conclusion Population-based PRS are strongly associated with BC and EOC risks forBRCA1/2carriers and predict substantial absolute risk differences for women at PRS distribution extremes. |
| format | Article |
| fullrecord | <record><control><sourceid>ghent</sourceid><recordid>TN_cdi_ghent_librecat_oai_archive_ugent_be_8670794</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>oai_archive_ugent_be_8670794</sourcerecordid><originalsourceid>FETCH-ghent_librecat_oai_archive_ugent_be_86707943</originalsourceid><addsrcrecordid>eNqdjUFuwjAQRb2gErTlDnMBJCdpk7IERNVlhdhbgztJplg2mjGI3r4QOAGr__S_nv7ITIr3ys5sVddj86z6a23RVKWdmPN3Cn8dRfYgrHtQn4QUMP7ATgg1D0gHzj0FxgDphMIYwWP0JIOk0Ca5FCJMopBaWG5Wi2Iwr1TCAXOfbi83PeureWoxKE3v-WLKz_V29TXreorZBb7ce8wuITsU3_OJ3LG7TjtyH3Vjm_lb9ZD0D5H-WOs</addsrcrecordid><sourcetype>Institutional Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants</title><source>Ghent University Academic Bibliography</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Barnes, Daniel R ; McGuffog, Lesley ; Mooij, Thea M ; Dennis, Joe ; Adlard, Julian ; Ahmed, Munaza ; Andrieu, Nadine ; Andrulis, Irene L ; Arun, Banu K ; Azzollini, Jacopo ; Balmaña, Judith ; Benitez, Javier ; Berthet, Pascaline ; Blanco, Amie M ; Blok, Marinus J ; Bradbury, Angela R ; Brennan, Paul ; Buys, Saundra S ; Caligo, Maria A ; Campbell, Ian ; Colas, Chrystelle ; Cook, Jackie ; Davidson, Rosemarie ; de Putter, Robin ; Delnatte, Capucine ; Devilee, Peter ; Ding, Yuan Chun ; Domchek, Susan M ; Ejlertsen, Bent ; Engel, Christoph ; Faivre, Laurence ; Friedman, Eitan ; Frost, Debra ; Gerdes, Anne-Marie ; Gesta, Paul ; Glendon, Gord ; Godwin, Andrew K ; Goldgar, David E ; Hamann, Ute ; Hogervorst, Frans B. L ; Horvath, Judit ; Hulick, Peter J ; Imyanitov, Evgeny N ; Isaacs, Claudine ; Izatt, Louise ; Izquierdo, Angel ; Jakubowska, Anna ; Janavicius, Ramunas ; Koudijs, Marco ; Kruse, Torben A ; Laitman, Yael ; Lazaro, Conxi ; Lesueur, Fabienne ; Loud, Jennifer T ; Lubiński, Jan ; Mebirouk, Noura ; Mensenkamp, Arjen R ; Montagna, Marco ; Mouret-Fourme, Emmanuelle ; Nathanson, Katherine L ; Osorio, Ana ; Ott, Claus-Eric ; Papi, Laura ; Park, Sue K ; Parsons, Michael T ; Peissel, Bernard ; Peterlongo, Paolo ; Pfeiler, Georg ; Prajzendanc, Karolina ; Radice, Paolo ; Ramser, Juliane ; Rantala, Johanna ; Rennert, Gad ; Risch, Harvey A ; Salani, Ritu ; Schuster, Hélène ; Shah, Payal D ; Sharma, Priyanka ; Singer, Christian F ; Slavin, Thomas P ; Spurdle, Amanda B ; Steinsnyder, Zoe ; Stoppa-Lyonnet, Dominique ; Tan, Yen Yen ; Teixeira, Manuel R ; Teo, Soo Hwang ; Thull, Darcy L ; Tognazzo, Silvia ; Toland, Amanda E ; Trainer, Alison H ; Tung, Nadine ; van Rensburg, Elizabeth J ; Wagner, Gabriel ; Yadav, Siddhartha ; Yannoukakos, Drakoulis ; Offit, Kenneth ; Thomassen, Mads ; Couch, Fergus J ; Schmutzler, Rita K ; Antoniou, Antonis C</creator><creatorcontrib>Barnes, Daniel R ; McGuffog, Lesley ; Mooij, Thea M ; Dennis, Joe ; Adlard, Julian ; Ahmed, Munaza ; Andrieu, Nadine ; Andrulis, Irene L ; Arun, Banu K ; Azzollini, Jacopo ; Balmaña, Judith ; Benitez, Javier ; Berthet, Pascaline ; Blanco, Amie M ; Blok, Marinus J ; Bradbury, Angela R ; Brennan, Paul ; Buys, Saundra S ; Caligo, Maria A ; Campbell, Ian ; Colas, Chrystelle ; Cook, Jackie ; Davidson, Rosemarie ; de Putter, Robin ; Delnatte, Capucine ; Devilee, Peter ; Ding, Yuan Chun ; Domchek, Susan M ; Ejlertsen, Bent ; Engel, Christoph ; Faivre, Laurence ; Friedman, Eitan ; Frost, Debra ; Gerdes, Anne-Marie ; Gesta, Paul ; Glendon, Gord ; Godwin, Andrew K ; Goldgar, David E ; Hamann, Ute ; Hogervorst, Frans B. L ; Horvath, Judit ; Hulick, Peter J ; Imyanitov, Evgeny N ; Isaacs, Claudine ; Izatt, Louise ; Izquierdo, Angel ; Jakubowska, Anna ; Janavicius, Ramunas ; Koudijs, Marco ; Kruse, Torben A ; Laitman, Yael ; Lazaro, Conxi ; Lesueur, Fabienne ; Loud, Jennifer T ; Lubiński, Jan ; Mebirouk, Noura ; Mensenkamp, Arjen R ; Montagna, Marco ; Mouret-Fourme, Emmanuelle ; Nathanson, Katherine L ; Osorio, Ana ; Ott, Claus-Eric ; Papi, Laura ; Park, Sue K ; Parsons, Michael T ; Peissel, Bernard ; Peterlongo, Paolo ; Pfeiler, Georg ; Prajzendanc, Karolina ; Radice, Paolo ; Ramser, Juliane ; Rantala, Johanna ; Rennert, Gad ; Risch, Harvey A ; Salani, Ritu ; Schuster, Hélène ; Shah, Payal D ; Sharma, Priyanka ; Singer, Christian F ; Slavin, Thomas P ; Spurdle, Amanda B ; Steinsnyder, Zoe ; Stoppa-Lyonnet, Dominique ; Tan, Yen Yen ; Teixeira, Manuel R ; Teo, Soo Hwang ; Thull, Darcy L ; Tognazzo, Silvia ; Toland, Amanda E ; Trainer, Alison H ; Tung, Nadine ; van Rensburg, Elizabeth J ; Wagner, Gabriel ; Yadav, Siddhartha ; Yannoukakos, Drakoulis ; Offit, Kenneth ; Thomassen, Mads ; Couch, Fergus J ; Schmutzler, Rita K ; Antoniou, Antonis C</creatorcontrib><description>Purpose We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks forBRCA1andBRCA2pathogenic variant carriers. Methods Retrospective cohort data on 18,935BRCA1and 12,339BRCA2female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results The ER-negative PRS showed the strongest association with BC risk forBRCA1carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33],P = 3x10(-72)). ForBRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36],P = 7x10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk forBRCA1(HR = 1.32 [95% CI 1.25-1.40],P = 3x10(-22)) andBRCA2(HR = 1.44 [95% CI 1.30-1.60],P = 4x10(-12)) carriers. The associations in the prospective cohort were similar. Conclusion Population-based PRS are strongly associated with BC and EOC risks forBRCA1/2carriers and predict substantial absolute risk differences for women at PRS distribution extremes.</description><identifier>ISSN: 1530-0366</identifier><identifier>ISSN: 1098-3600</identifier><language>eng</language><subject>ALLELES ; ASSOCIATION ; BRCA1 ; BRCA2 ; breast cancer ; genetics ; Genetics(clinical) ; IDENTIFICATION ; Medicine and Health Sciences ; MODIFIERS ; MUTATION CARRIERS ; ovarian cancer ; PATHOLOGY ; PRS ; SUSCEPTIBILITY</subject><creationdate>2020</creationdate><rights>Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) info:eu-repo/semantics/openAccess</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,315,776,780,4010,27837</link.rule.ids></links><search><creatorcontrib>Barnes, Daniel R</creatorcontrib><creatorcontrib>McGuffog, Lesley</creatorcontrib><creatorcontrib>Mooij, Thea M</creatorcontrib><creatorcontrib>Dennis, Joe</creatorcontrib><creatorcontrib>Adlard, Julian</creatorcontrib><creatorcontrib>Ahmed, Munaza</creatorcontrib><creatorcontrib>Andrieu, Nadine</creatorcontrib><creatorcontrib>Andrulis, Irene L</creatorcontrib><creatorcontrib>Arun, Banu K</creatorcontrib><creatorcontrib>Azzollini, Jacopo</creatorcontrib><creatorcontrib>Balmaña, Judith</creatorcontrib><creatorcontrib>Benitez, Javier</creatorcontrib><creatorcontrib>Berthet, Pascaline</creatorcontrib><creatorcontrib>Blanco, Amie M</creatorcontrib><creatorcontrib>Blok, Marinus J</creatorcontrib><creatorcontrib>Bradbury, Angela R</creatorcontrib><creatorcontrib>Brennan, Paul</creatorcontrib><creatorcontrib>Buys, Saundra S</creatorcontrib><creatorcontrib>Caligo, Maria A</creatorcontrib><creatorcontrib>Campbell, Ian</creatorcontrib><creatorcontrib>Colas, Chrystelle</creatorcontrib><creatorcontrib>Cook, Jackie</creatorcontrib><creatorcontrib>Davidson, Rosemarie</creatorcontrib><creatorcontrib>de Putter, Robin</creatorcontrib><creatorcontrib>Delnatte, Capucine</creatorcontrib><creatorcontrib>Devilee, Peter</creatorcontrib><creatorcontrib>Ding, Yuan Chun</creatorcontrib><creatorcontrib>Domchek, Susan M</creatorcontrib><creatorcontrib>Ejlertsen, Bent</creatorcontrib><creatorcontrib>Engel, Christoph</creatorcontrib><creatorcontrib>Faivre, Laurence</creatorcontrib><creatorcontrib>Friedman, Eitan</creatorcontrib><creatorcontrib>Frost, Debra</creatorcontrib><creatorcontrib>Gerdes, Anne-Marie</creatorcontrib><creatorcontrib>Gesta, Paul</creatorcontrib><creatorcontrib>Glendon, Gord</creatorcontrib><creatorcontrib>Godwin, Andrew K</creatorcontrib><creatorcontrib>Goldgar, David E</creatorcontrib><creatorcontrib>Hamann, Ute</creatorcontrib><creatorcontrib>Hogervorst, Frans B. L</creatorcontrib><creatorcontrib>Horvath, Judit</creatorcontrib><creatorcontrib>Hulick, Peter J</creatorcontrib><creatorcontrib>Imyanitov, Evgeny N</creatorcontrib><creatorcontrib>Isaacs, Claudine</creatorcontrib><creatorcontrib>Izatt, Louise</creatorcontrib><creatorcontrib>Izquierdo, Angel</creatorcontrib><creatorcontrib>Jakubowska, Anna</creatorcontrib><creatorcontrib>Janavicius, Ramunas</creatorcontrib><creatorcontrib>Koudijs, Marco</creatorcontrib><creatorcontrib>Kruse, Torben A</creatorcontrib><creatorcontrib>Laitman, Yael</creatorcontrib><creatorcontrib>Lazaro, Conxi</creatorcontrib><creatorcontrib>Lesueur, Fabienne</creatorcontrib><creatorcontrib>Loud, Jennifer T</creatorcontrib><creatorcontrib>Lubiński, Jan</creatorcontrib><creatorcontrib>Mebirouk, Noura</creatorcontrib><creatorcontrib>Mensenkamp, Arjen R</creatorcontrib><creatorcontrib>Montagna, Marco</creatorcontrib><creatorcontrib>Mouret-Fourme, Emmanuelle</creatorcontrib><creatorcontrib>Nathanson, Katherine L</creatorcontrib><creatorcontrib>Osorio, Ana</creatorcontrib><creatorcontrib>Ott, Claus-Eric</creatorcontrib><creatorcontrib>Papi, Laura</creatorcontrib><creatorcontrib>Park, Sue K</creatorcontrib><creatorcontrib>Parsons, Michael T</creatorcontrib><creatorcontrib>Peissel, Bernard</creatorcontrib><creatorcontrib>Peterlongo, Paolo</creatorcontrib><creatorcontrib>Pfeiler, Georg</creatorcontrib><creatorcontrib>Prajzendanc, Karolina</creatorcontrib><creatorcontrib>Radice, Paolo</creatorcontrib><creatorcontrib>Ramser, Juliane</creatorcontrib><creatorcontrib>Rantala, Johanna</creatorcontrib><creatorcontrib>Rennert, Gad</creatorcontrib><creatorcontrib>Risch, Harvey A</creatorcontrib><creatorcontrib>Salani, Ritu</creatorcontrib><creatorcontrib>Schuster, Hélène</creatorcontrib><creatorcontrib>Shah, Payal D</creatorcontrib><creatorcontrib>Sharma, Priyanka</creatorcontrib><creatorcontrib>Singer, Christian F</creatorcontrib><creatorcontrib>Slavin, Thomas P</creatorcontrib><creatorcontrib>Spurdle, Amanda B</creatorcontrib><creatorcontrib>Steinsnyder, Zoe</creatorcontrib><creatorcontrib>Stoppa-Lyonnet, Dominique</creatorcontrib><creatorcontrib>Tan, Yen Yen</creatorcontrib><creatorcontrib>Teixeira, Manuel R</creatorcontrib><creatorcontrib>Teo, Soo Hwang</creatorcontrib><creatorcontrib>Thull, Darcy L</creatorcontrib><creatorcontrib>Tognazzo, Silvia</creatorcontrib><creatorcontrib>Toland, Amanda E</creatorcontrib><creatorcontrib>Trainer, Alison H</creatorcontrib><creatorcontrib>Tung, Nadine</creatorcontrib><creatorcontrib>van Rensburg, Elizabeth J</creatorcontrib><creatorcontrib>Wagner, Gabriel</creatorcontrib><creatorcontrib>Yadav, Siddhartha</creatorcontrib><creatorcontrib>Yannoukakos, Drakoulis</creatorcontrib><creatorcontrib>Offit, Kenneth</creatorcontrib><creatorcontrib>Thomassen, Mads</creatorcontrib><creatorcontrib>Couch, Fergus J</creatorcontrib><creatorcontrib>Schmutzler, Rita K</creatorcontrib><creatorcontrib>Antoniou, Antonis C</creatorcontrib><title>Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants</title><description>Purpose We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks forBRCA1andBRCA2pathogenic variant carriers. Methods Retrospective cohort data on 18,935BRCA1and 12,339BRCA2female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results The ER-negative PRS showed the strongest association with BC risk forBRCA1carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33],P = 3x10(-72)). ForBRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36],P = 7x10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk forBRCA1(HR = 1.32 [95% CI 1.25-1.40],P = 3x10(-22)) andBRCA2(HR = 1.44 [95% CI 1.30-1.60],P = 4x10(-12)) carriers. The associations in the prospective cohort were similar. Conclusion Population-based PRS are strongly associated with BC and EOC risks forBRCA1/2carriers and predict substantial absolute risk differences for women at PRS distribution extremes.</description><subject>ALLELES</subject><subject>ASSOCIATION</subject><subject>BRCA1</subject><subject>BRCA2</subject><subject>breast cancer</subject><subject>genetics</subject><subject>Genetics(clinical)</subject><subject>IDENTIFICATION</subject><subject>Medicine and Health Sciences</subject><subject>MODIFIERS</subject><subject>MUTATION CARRIERS</subject><subject>ovarian cancer</subject><subject>PATHOLOGY</subject><subject>PRS</subject><subject>SUSCEPTIBILITY</subject><issn>1530-0366</issn><issn>1098-3600</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>ADGLB</sourceid><recordid>eNqdjUFuwjAQRb2gErTlDnMBJCdpk7IERNVlhdhbgztJplg2mjGI3r4QOAGr__S_nv7ITIr3ys5sVddj86z6a23RVKWdmPN3Cn8dRfYgrHtQn4QUMP7ATgg1D0gHzj0FxgDphMIYwWP0JIOk0Ca5FCJMopBaWG5Wi2Iwr1TCAXOfbi83PeureWoxKE3v-WLKz_V29TXreorZBb7ce8wuITsU3_OJ3LG7TjtyH3Vjm_lb9ZD0D5H-WOs</recordid><startdate>2020</startdate><enddate>2020</enddate><creator>Barnes, Daniel R</creator><creator>McGuffog, Lesley</creator><creator>Mooij, Thea M</creator><creator>Dennis, Joe</creator><creator>Adlard, Julian</creator><creator>Ahmed, Munaza</creator><creator>Andrieu, Nadine</creator><creator>Andrulis, Irene L</creator><creator>Arun, Banu K</creator><creator>Azzollini, Jacopo</creator><creator>Balmaña, Judith</creator><creator>Benitez, Javier</creator><creator>Berthet, Pascaline</creator><creator>Blanco, Amie M</creator><creator>Blok, Marinus J</creator><creator>Bradbury, Angela R</creator><creator>Brennan, Paul</creator><creator>Buys, Saundra S</creator><creator>Caligo, Maria A</creator><creator>Campbell, Ian</creator><creator>Colas, Chrystelle</creator><creator>Cook, Jackie</creator><creator>Davidson, Rosemarie</creator><creator>de Putter, Robin</creator><creator>Delnatte, Capucine</creator><creator>Devilee, Peter</creator><creator>Ding, Yuan Chun</creator><creator>Domchek, Susan M</creator><creator>Ejlertsen, Bent</creator><creator>Engel, Christoph</creator><creator>Faivre, Laurence</creator><creator>Friedman, Eitan</creator><creator>Frost, Debra</creator><creator>Gerdes, Anne-Marie</creator><creator>Gesta, Paul</creator><creator>Glendon, Gord</creator><creator>Godwin, Andrew K</creator><creator>Goldgar, David E</creator><creator>Hamann, Ute</creator><creator>Hogervorst, Frans B. L</creator><creator>Horvath, Judit</creator><creator>Hulick, Peter J</creator><creator>Imyanitov, Evgeny N</creator><creator>Isaacs, Claudine</creator><creator>Izatt, Louise</creator><creator>Izquierdo, Angel</creator><creator>Jakubowska, Anna</creator><creator>Janavicius, Ramunas</creator><creator>Koudijs, Marco</creator><creator>Kruse, Torben A</creator><creator>Laitman, Yael</creator><creator>Lazaro, Conxi</creator><creator>Lesueur, Fabienne</creator><creator>Loud, Jennifer T</creator><creator>Lubiński, Jan</creator><creator>Mebirouk, Noura</creator><creator>Mensenkamp, Arjen R</creator><creator>Montagna, Marco</creator><creator>Mouret-Fourme, Emmanuelle</creator><creator>Nathanson, Katherine L</creator><creator>Osorio, Ana</creator><creator>Ott, Claus-Eric</creator><creator>Papi, Laura</creator><creator>Park, Sue K</creator><creator>Parsons, Michael T</creator><creator>Peissel, Bernard</creator><creator>Peterlongo, Paolo</creator><creator>Pfeiler, Georg</creator><creator>Prajzendanc, Karolina</creator><creator>Radice, Paolo</creator><creator>Ramser, Juliane</creator><creator>Rantala, Johanna</creator><creator>Rennert, Gad</creator><creator>Risch, Harvey A</creator><creator>Salani, Ritu</creator><creator>Schuster, Hélène</creator><creator>Shah, Payal D</creator><creator>Sharma, Priyanka</creator><creator>Singer, Christian F</creator><creator>Slavin, Thomas P</creator><creator>Spurdle, Amanda B</creator><creator>Steinsnyder, Zoe</creator><creator>Stoppa-Lyonnet, Dominique</creator><creator>Tan, Yen Yen</creator><creator>Teixeira, Manuel R</creator><creator>Teo, Soo Hwang</creator><creator>Thull, Darcy L</creator><creator>Tognazzo, Silvia</creator><creator>Toland, Amanda E</creator><creator>Trainer, Alison H</creator><creator>Tung, Nadine</creator><creator>van Rensburg, Elizabeth J</creator><creator>Wagner, Gabriel</creator><creator>Yadav, Siddhartha</creator><creator>Yannoukakos, Drakoulis</creator><creator>Offit, Kenneth</creator><creator>Thomassen, Mads</creator><creator>Couch, Fergus J</creator><creator>Schmutzler, Rita K</creator><creator>Antoniou, Antonis C</creator><scope>ADGLB</scope></search><sort><creationdate>2020</creationdate><title>Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants</title><author>Barnes, Daniel R ; McGuffog, Lesley ; Mooij, Thea M ; Dennis, Joe ; Adlard, Julian ; Ahmed, Munaza ; Andrieu, Nadine ; Andrulis, Irene L ; Arun, Banu K ; Azzollini, Jacopo ; Balmaña, Judith ; Benitez, Javier ; Berthet, Pascaline ; Blanco, Amie M ; Blok, Marinus J ; Bradbury, Angela R ; Brennan, Paul ; Buys, Saundra S ; Caligo, Maria A ; Campbell, Ian ; Colas, Chrystelle ; Cook, Jackie ; Davidson, Rosemarie ; de Putter, Robin ; Delnatte, Capucine ; Devilee, Peter ; Ding, Yuan Chun ; Domchek, Susan M ; Ejlertsen, Bent ; Engel, Christoph ; Faivre, Laurence ; Friedman, Eitan ; Frost, Debra ; Gerdes, Anne-Marie ; Gesta, Paul ; Glendon, Gord ; Godwin, Andrew K ; Goldgar, David E ; Hamann, Ute ; Hogervorst, Frans B. L ; Horvath, Judit ; Hulick, Peter J ; Imyanitov, Evgeny N ; Isaacs, Claudine ; Izatt, Louise ; Izquierdo, Angel ; Jakubowska, Anna ; Janavicius, Ramunas ; Koudijs, Marco ; Kruse, Torben A ; Laitman, Yael ; Lazaro, Conxi ; Lesueur, Fabienne ; Loud, Jennifer T ; Lubiński, Jan ; Mebirouk, Noura ; Mensenkamp, Arjen R ; Montagna, Marco ; Mouret-Fourme, Emmanuelle ; Nathanson, Katherine L ; Osorio, Ana ; Ott, Claus-Eric ; Papi, Laura ; Park, Sue K ; Parsons, Michael T ; Peissel, Bernard ; Peterlongo, Paolo ; Pfeiler, Georg ; Prajzendanc, Karolina ; Radice, Paolo ; Ramser, Juliane ; Rantala, Johanna ; Rennert, Gad ; Risch, Harvey A ; Salani, Ritu ; Schuster, Hélène ; Shah, Payal D ; Sharma, Priyanka ; Singer, Christian F ; Slavin, Thomas P ; Spurdle, Amanda B ; Steinsnyder, Zoe ; Stoppa-Lyonnet, Dominique ; Tan, Yen Yen ; Teixeira, Manuel R ; Teo, Soo Hwang ; Thull, Darcy L ; Tognazzo, Silvia ; Toland, Amanda E ; Trainer, Alison H ; Tung, Nadine ; van Rensburg, Elizabeth J ; Wagner, Gabriel ; Yadav, Siddhartha ; Yannoukakos, Drakoulis ; Offit, Kenneth ; Thomassen, Mads ; Couch, Fergus J ; Schmutzler, Rita K ; Antoniou, Antonis C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-ghent_librecat_oai_archive_ugent_be_86707943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>ALLELES</topic><topic>ASSOCIATION</topic><topic>BRCA1</topic><topic>BRCA2</topic><topic>breast cancer</topic><topic>genetics</topic><topic>Genetics(clinical)</topic><topic>IDENTIFICATION</topic><topic>Medicine and Health Sciences</topic><topic>MODIFIERS</topic><topic>MUTATION CARRIERS</topic><topic>ovarian cancer</topic><topic>PATHOLOGY</topic><topic>PRS</topic><topic>SUSCEPTIBILITY</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barnes, Daniel R</creatorcontrib><creatorcontrib>McGuffog, Lesley</creatorcontrib><creatorcontrib>Mooij, Thea M</creatorcontrib><creatorcontrib>Dennis, Joe</creatorcontrib><creatorcontrib>Adlard, Julian</creatorcontrib><creatorcontrib>Ahmed, Munaza</creatorcontrib><creatorcontrib>Andrieu, Nadine</creatorcontrib><creatorcontrib>Andrulis, Irene L</creatorcontrib><creatorcontrib>Arun, Banu K</creatorcontrib><creatorcontrib>Azzollini, Jacopo</creatorcontrib><creatorcontrib>Balmaña, Judith</creatorcontrib><creatorcontrib>Benitez, Javier</creatorcontrib><creatorcontrib>Berthet, Pascaline</creatorcontrib><creatorcontrib>Blanco, Amie M</creatorcontrib><creatorcontrib>Blok, Marinus J</creatorcontrib><creatorcontrib>Bradbury, Angela R</creatorcontrib><creatorcontrib>Brennan, Paul</creatorcontrib><creatorcontrib>Buys, Saundra S</creatorcontrib><creatorcontrib>Caligo, Maria A</creatorcontrib><creatorcontrib>Campbell, Ian</creatorcontrib><creatorcontrib>Colas, Chrystelle</creatorcontrib><creatorcontrib>Cook, Jackie</creatorcontrib><creatorcontrib>Davidson, Rosemarie</creatorcontrib><creatorcontrib>de Putter, Robin</creatorcontrib><creatorcontrib>Delnatte, Capucine</creatorcontrib><creatorcontrib>Devilee, Peter</creatorcontrib><creatorcontrib>Ding, Yuan Chun</creatorcontrib><creatorcontrib>Domchek, Susan M</creatorcontrib><creatorcontrib>Ejlertsen, Bent</creatorcontrib><creatorcontrib>Engel, Christoph</creatorcontrib><creatorcontrib>Faivre, Laurence</creatorcontrib><creatorcontrib>Friedman, Eitan</creatorcontrib><creatorcontrib>Frost, Debra</creatorcontrib><creatorcontrib>Gerdes, Anne-Marie</creatorcontrib><creatorcontrib>Gesta, Paul</creatorcontrib><creatorcontrib>Glendon, Gord</creatorcontrib><creatorcontrib>Godwin, Andrew K</creatorcontrib><creatorcontrib>Goldgar, David E</creatorcontrib><creatorcontrib>Hamann, Ute</creatorcontrib><creatorcontrib>Hogervorst, Frans B. L</creatorcontrib><creatorcontrib>Horvath, Judit</creatorcontrib><creatorcontrib>Hulick, Peter J</creatorcontrib><creatorcontrib>Imyanitov, Evgeny N</creatorcontrib><creatorcontrib>Isaacs, Claudine</creatorcontrib><creatorcontrib>Izatt, Louise</creatorcontrib><creatorcontrib>Izquierdo, Angel</creatorcontrib><creatorcontrib>Jakubowska, Anna</creatorcontrib><creatorcontrib>Janavicius, Ramunas</creatorcontrib><creatorcontrib>Koudijs, Marco</creatorcontrib><creatorcontrib>Kruse, Torben A</creatorcontrib><creatorcontrib>Laitman, Yael</creatorcontrib><creatorcontrib>Lazaro, Conxi</creatorcontrib><creatorcontrib>Lesueur, Fabienne</creatorcontrib><creatorcontrib>Loud, Jennifer T</creatorcontrib><creatorcontrib>Lubiński, Jan</creatorcontrib><creatorcontrib>Mebirouk, Noura</creatorcontrib><creatorcontrib>Mensenkamp, Arjen R</creatorcontrib><creatorcontrib>Montagna, Marco</creatorcontrib><creatorcontrib>Mouret-Fourme, Emmanuelle</creatorcontrib><creatorcontrib>Nathanson, Katherine L</creatorcontrib><creatorcontrib>Osorio, Ana</creatorcontrib><creatorcontrib>Ott, Claus-Eric</creatorcontrib><creatorcontrib>Papi, Laura</creatorcontrib><creatorcontrib>Park, Sue K</creatorcontrib><creatorcontrib>Parsons, Michael T</creatorcontrib><creatorcontrib>Peissel, Bernard</creatorcontrib><creatorcontrib>Peterlongo, Paolo</creatorcontrib><creatorcontrib>Pfeiler, Georg</creatorcontrib><creatorcontrib>Prajzendanc, Karolina</creatorcontrib><creatorcontrib>Radice, Paolo</creatorcontrib><creatorcontrib>Ramser, Juliane</creatorcontrib><creatorcontrib>Rantala, Johanna</creatorcontrib><creatorcontrib>Rennert, Gad</creatorcontrib><creatorcontrib>Risch, Harvey A</creatorcontrib><creatorcontrib>Salani, Ritu</creatorcontrib><creatorcontrib>Schuster, Hélène</creatorcontrib><creatorcontrib>Shah, Payal D</creatorcontrib><creatorcontrib>Sharma, Priyanka</creatorcontrib><creatorcontrib>Singer, Christian F</creatorcontrib><creatorcontrib>Slavin, Thomas P</creatorcontrib><creatorcontrib>Spurdle, Amanda B</creatorcontrib><creatorcontrib>Steinsnyder, Zoe</creatorcontrib><creatorcontrib>Stoppa-Lyonnet, Dominique</creatorcontrib><creatorcontrib>Tan, Yen Yen</creatorcontrib><creatorcontrib>Teixeira, Manuel R</creatorcontrib><creatorcontrib>Teo, Soo Hwang</creatorcontrib><creatorcontrib>Thull, Darcy L</creatorcontrib><creatorcontrib>Tognazzo, Silvia</creatorcontrib><creatorcontrib>Toland, Amanda E</creatorcontrib><creatorcontrib>Trainer, Alison H</creatorcontrib><creatorcontrib>Tung, Nadine</creatorcontrib><creatorcontrib>van Rensburg, Elizabeth J</creatorcontrib><creatorcontrib>Wagner, Gabriel</creatorcontrib><creatorcontrib>Yadav, Siddhartha</creatorcontrib><creatorcontrib>Yannoukakos, Drakoulis</creatorcontrib><creatorcontrib>Offit, Kenneth</creatorcontrib><creatorcontrib>Thomassen, Mads</creatorcontrib><creatorcontrib>Couch, Fergus J</creatorcontrib><creatorcontrib>Schmutzler, Rita K</creatorcontrib><creatorcontrib>Antoniou, Antonis C</creatorcontrib><collection>Ghent University Academic Bibliography</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barnes, Daniel R</au><au>McGuffog, Lesley</au><au>Mooij, Thea M</au><au>Dennis, Joe</au><au>Adlard, Julian</au><au>Ahmed, Munaza</au><au>Andrieu, Nadine</au><au>Andrulis, Irene L</au><au>Arun, Banu K</au><au>Azzollini, Jacopo</au><au>Balmaña, Judith</au><au>Benitez, Javier</au><au>Berthet, Pascaline</au><au>Blanco, Amie M</au><au>Blok, Marinus J</au><au>Bradbury, Angela R</au><au>Brennan, Paul</au><au>Buys, Saundra S</au><au>Caligo, Maria A</au><au>Campbell, Ian</au><au>Colas, Chrystelle</au><au>Cook, Jackie</au><au>Davidson, Rosemarie</au><au>de Putter, Robin</au><au>Delnatte, Capucine</au><au>Devilee, Peter</au><au>Ding, Yuan Chun</au><au>Domchek, Susan M</au><au>Ejlertsen, Bent</au><au>Engel, Christoph</au><au>Faivre, Laurence</au><au>Friedman, Eitan</au><au>Frost, Debra</au><au>Gerdes, Anne-Marie</au><au>Gesta, Paul</au><au>Glendon, Gord</au><au>Godwin, Andrew K</au><au>Goldgar, David E</au><au>Hamann, Ute</au><au>Hogervorst, Frans B. L</au><au>Horvath, Judit</au><au>Hulick, Peter J</au><au>Imyanitov, Evgeny N</au><au>Isaacs, Claudine</au><au>Izatt, Louise</au><au>Izquierdo, Angel</au><au>Jakubowska, Anna</au><au>Janavicius, Ramunas</au><au>Koudijs, Marco</au><au>Kruse, Torben A</au><au>Laitman, Yael</au><au>Lazaro, Conxi</au><au>Lesueur, Fabienne</au><au>Loud, Jennifer T</au><au>Lubiński, Jan</au><au>Mebirouk, Noura</au><au>Mensenkamp, Arjen R</au><au>Montagna, Marco</au><au>Mouret-Fourme, Emmanuelle</au><au>Nathanson, Katherine L</au><au>Osorio, Ana</au><au>Ott, Claus-Eric</au><au>Papi, Laura</au><au>Park, Sue K</au><au>Parsons, Michael T</au><au>Peissel, Bernard</au><au>Peterlongo, Paolo</au><au>Pfeiler, Georg</au><au>Prajzendanc, Karolina</au><au>Radice, Paolo</au><au>Ramser, Juliane</au><au>Rantala, Johanna</au><au>Rennert, Gad</au><au>Risch, Harvey A</au><au>Salani, Ritu</au><au>Schuster, Hélène</au><au>Shah, Payal D</au><au>Sharma, Priyanka</au><au>Singer, Christian F</au><au>Slavin, Thomas P</au><au>Spurdle, Amanda B</au><au>Steinsnyder, Zoe</au><au>Stoppa-Lyonnet, Dominique</au><au>Tan, Yen Yen</au><au>Teixeira, Manuel R</au><au>Teo, Soo Hwang</au><au>Thull, Darcy L</au><au>Tognazzo, Silvia</au><au>Toland, Amanda E</au><au>Trainer, Alison H</au><au>Tung, Nadine</au><au>van Rensburg, Elizabeth J</au><au>Wagner, Gabriel</au><au>Yadav, Siddhartha</au><au>Yannoukakos, Drakoulis</au><au>Offit, Kenneth</au><au>Thomassen, Mads</au><au>Couch, Fergus J</au><au>Schmutzler, Rita K</au><au>Antoniou, Antonis C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants</atitle><date>2020</date><risdate>2020</risdate><issn>1530-0366</issn><issn>1098-3600</issn><abstract>Purpose We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks forBRCA1andBRCA2pathogenic variant carriers. Methods Retrospective cohort data on 18,935BRCA1and 12,339BRCA2female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results The ER-negative PRS showed the strongest association with BC risk forBRCA1carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33],P = 3x10(-72)). ForBRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36],P = 7x10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk forBRCA1(HR = 1.32 [95% CI 1.25-1.40],P = 3x10(-22)) andBRCA2(HR = 1.44 [95% CI 1.30-1.60],P = 4x10(-12)) carriers. The associations in the prospective cohort were similar. Conclusion Population-based PRS are strongly associated with BC and EOC risks forBRCA1/2carriers and predict substantial absolute risk differences for women at PRS distribution extremes.</abstract><oa>free_for_read</oa></addata></record> |
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| source | Ghent University Academic Bibliography; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | ALLELES ASSOCIATION BRCA1 BRCA2 breast cancer genetics Genetics(clinical) IDENTIFICATION Medicine and Health Sciences MODIFIERS MUTATION CARRIERS ovarian cancer PATHOLOGY PRS SUSCEPTIBILITY |
| title | Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants |
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