Breast cancer risks associated with missense variants in breast cancer susceptibility genes
Q1
- Autores:
-
Dorling, Leila
Carvalho, Sara
Allen, Jamie
Parsons, Michael T.
Fortuno, Cristina
González-Neira, Anna
Heijl, Stephan M.
Adank, Muriel A.
Ahearn, Thomas U.
Andrulis, Irene L.
Auvinen, Päivi
Becher, Heiko
Beckmann, Matthias W.
Behrens, Sabine
Bermisheva, Marina
Bogdanova, Natalia V.
Bojesen, Stig E.
Bolla, Manjeet K.
Bremer, Michael
Camp, Nicola J.
Campbell, Archie
Castelao, Jose E.
Chang-Claude, Jenny
Chanock, Stephen J.
Chenevix-Trench, Georgia
NBCS Collaborators
Collée, J. Margriet
Czene, Kamila
Dennis, Joe
Dörk, Thilo
Eriksson, Mikael
Evans, Gareth D.
Fasching, Peter A.
Figueroa, Jonine
Flyger, Henrik
Gabrielson, Marike
Gago-Dominguez, Manuela
García-Closas, Montserrat
Giles, Graham G.
Glendon, Gord
Guénel, Pascal
Gündert, Melanie
Hadjisavvas, Andreas
Hahnen, Eric
Hall, Per
Hamann, Ute
Harkness, Elaine F.
Hartman, Mikael
Hogervorst, Frans B. L.
Hollestelle, Antoinette
Hoppe, Reiner
Howell, Anthony
kConFab Investigators
SGBCC Investigators
Jakubowska, Anna
Jung, Audrey
Khusnutdinova, Elza
Kim, Sung-Won
Ko, Yon-Dschun
Kristensen, Vessela N.
Lakeman, Inge M. M.
Li, Jingmei
Lindblom, Annika
Loizidou, Maria A.
Lophatananon, Artitaya
Lubiński, Jan
Luccarini, Craig
Madsen, Michael J.
Mannermaa, Arto
Manoochehri, Mehdi
Margolin, Sara
Mavroudis, Dimitrios
Milne, Roger L.
Mohd Taib, Nur Aishah
Muir, Kenneth
Nevanlinna, Heli
Newman, William G.
Oosterwijk, Jan C.
Park, Sue K.
Peterlongo, Paolo
Radice, Paolo
Saloustros, Emmanouil
Sawyer, Elinor J.
Schmutzler, Rita K.
Shah, Mitul
Sim, Xueling
Southey, Melissa C.
Surowy, Harald
Suvanto, Maija
Tomlinson, Ian
Truong, Thérèse
van Asperen, Christi J.
Waltes, Regina
Wang, Qin
Yang, Xiaohong R.
Pharoah, Paul D. P.
Schmidt, Marjanka K.
Benitez, Javier
Vroling, Bas
Dunning, Alison M.
Teo, Soo Hwang
Kvist, Anders
de la Hoya, Miguel
Devilee, Peter
Spurdle, Amanda B.
Vreeswijk, Maaike P.G.
Easton, Douglas F.
Briceño Balcázar, Ignacio
Torres-López, Diana María
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2022
- Institución:
- Pontificia Universidad Javeriana
- Repositorio:
- Repositorio Universidad Javeriana
- Idioma:
- eng
- OAI Identifier:
- oai:repository.javeriana.edu.co:10554/62117
- Acceso en línea:
- https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-022-01052-8
http://hdl.handle.net/10554/62117
https://doi.org/10.1186/s13073-022-01052-8
- Palabra clave:
- Breast cancer
Genetic epidemiology
Risk prediction
Missense variants
- Rights
- License
- Atribución-NoComercial 4.0 Internacional
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| dc.title.spa.fl_str_mv |
Breast cancer risks associated with missense variants in breast cancer susceptibility genes |
| title |
Breast cancer risks associated with missense variants in breast cancer susceptibility genes |
| spellingShingle |
Breast cancer risks associated with missense variants in breast cancer susceptibility genes Breast cancer Genetic epidemiology Risk prediction Missense variants |
| title_short |
Breast cancer risks associated with missense variants in breast cancer susceptibility genes |
| title_full |
Breast cancer risks associated with missense variants in breast cancer susceptibility genes |
| title_fullStr |
Breast cancer risks associated with missense variants in breast cancer susceptibility genes |
| title_full_unstemmed |
Breast cancer risks associated with missense variants in breast cancer susceptibility genes |
| title_sort |
Breast cancer risks associated with missense variants in breast cancer susceptibility genes |
| dc.creator.fl_str_mv |
Dorling, Leila Carvalho, Sara Allen, Jamie Parsons, Michael T. Fortuno, Cristina González-Neira, Anna Heijl, Stephan M. Adank, Muriel A. Ahearn, Thomas U. Andrulis, Irene L. Auvinen, Päivi Becher, Heiko Beckmann, Matthias W. Behrens, Sabine Bermisheva, Marina Bogdanova, Natalia V. Bojesen, Stig E. Bolla, Manjeet K. Bremer, Michael Camp, Nicola J. Campbell, Archie Castelao, Jose E. Chang-Claude, Jenny Chanock, Stephen J. Chenevix-Trench, Georgia NBCS Collaborators Collée, J. Margriet Czene, Kamila Dennis, Joe Dörk, Thilo Eriksson, Mikael Evans, Gareth D. Fasching, Peter A. Figueroa, Jonine Flyger, Henrik Gabrielson, Marike Gago-Dominguez, Manuela García-Closas, Montserrat Giles, Graham G. Glendon, Gord Guénel, Pascal Gündert, Melanie Hadjisavvas, Andreas Hahnen, Eric Hall, Per Hamann, Ute Harkness, Elaine F. Hartman, Mikael Hogervorst, Frans B. L. Hollestelle, Antoinette Hoppe, Reiner Howell, Anthony kConFab Investigators SGBCC Investigators Jakubowska, Anna Jung, Audrey Khusnutdinova, Elza Kim, Sung-Won Ko, Yon-Dschun Kristensen, Vessela N. Lakeman, Inge M. M. Li, Jingmei Lindblom, Annika Loizidou, Maria A. Lophatananon, Artitaya Lubiński, Jan Luccarini, Craig Madsen, Michael J. Mannermaa, Arto Manoochehri, Mehdi Margolin, Sara Mavroudis, Dimitrios Milne, Roger L. Mohd Taib, Nur Aishah Muir, Kenneth Nevanlinna, Heli Newman, William G. Oosterwijk, Jan C. Park, Sue K. Peterlongo, Paolo Radice, Paolo Saloustros, Emmanouil Sawyer, Elinor J. Schmutzler, Rita K. Shah, Mitul Sim, Xueling Southey, Melissa C. Surowy, Harald Suvanto, Maija Tomlinson, Ian Truong, Thérèse van Asperen, Christi J. Waltes, Regina Wang, Qin Yang, Xiaohong R. Pharoah, Paul D. P. Schmidt, Marjanka K. Benitez, Javier Vroling, Bas Dunning, Alison M. Teo, Soo Hwang Kvist, Anders de la Hoya, Miguel Devilee, Peter Spurdle, Amanda B. Vreeswijk, Maaike P.G. Easton, Douglas F. Briceño Balcázar, Ignacio Torres-López, Diana María |
| dc.contributor.author.none.fl_str_mv |
Dorling, Leila Carvalho, Sara Allen, Jamie Parsons, Michael T. Fortuno, Cristina González-Neira, Anna Heijl, Stephan M. Adank, Muriel A. Ahearn, Thomas U. Andrulis, Irene L. Auvinen, Päivi Becher, Heiko Beckmann, Matthias W. Behrens, Sabine Bermisheva, Marina Bogdanova, Natalia V. Bojesen, Stig E. Bolla, Manjeet K. Bremer, Michael Camp, Nicola J. Campbell, Archie Castelao, Jose E. Chang-Claude, Jenny Chanock, Stephen J. Chenevix-Trench, Georgia NBCS Collaborators Collée, J. Margriet Czene, Kamila Dennis, Joe Dörk, Thilo Eriksson, Mikael Evans, Gareth D. Fasching, Peter A. Figueroa, Jonine Flyger, Henrik Gabrielson, Marike Gago-Dominguez, Manuela García-Closas, Montserrat Giles, Graham G. Glendon, Gord Guénel, Pascal Gündert, Melanie Hadjisavvas, Andreas Hahnen, Eric Hall, Per Hamann, Ute Harkness, Elaine F. Hartman, Mikael Hogervorst, Frans B. L. Hollestelle, Antoinette Hoppe, Reiner Howell, Anthony kConFab Investigators SGBCC Investigators Jakubowska, Anna Jung, Audrey Khusnutdinova, Elza Kim, Sung-Won Ko, Yon-Dschun Kristensen, Vessela N. Lakeman, Inge M. M. Li, Jingmei Lindblom, Annika Loizidou, Maria A. Lophatananon, Artitaya Lubiński, Jan Luccarini, Craig Madsen, Michael J. Mannermaa, Arto Manoochehri, Mehdi Margolin, Sara Mavroudis, Dimitrios Milne, Roger L. Mohd Taib, Nur Aishah Muir, Kenneth Nevanlinna, Heli Newman, William G. Oosterwijk, Jan C. Park, Sue K. Peterlongo, Paolo Radice, Paolo Saloustros, Emmanouil Sawyer, Elinor J. Schmutzler, Rita K. Shah, Mitul Sim, Xueling Southey, Melissa C. Surowy, Harald Suvanto, Maija Tomlinson, Ian Truong, Thérèse van Asperen, Christi J. Waltes, Regina Wang, Qin Yang, Xiaohong R. Pharoah, Paul D. P. Schmidt, Marjanka K. Benitez, Javier Vroling, Bas Dunning, Alison M. Teo, Soo Hwang Kvist, Anders de la Hoya, Miguel Devilee, Peter Spurdle, Amanda B. Vreeswijk, Maaike P.G. Easton, Douglas F. Briceño Balcázar, Ignacio Torres-López, Diana María |
| dc.contributor.corporatename.spa.fl_str_mv |
Pontificia Universidad Javeriana. Facultad de Medicina. Instituto de Genética Humana. Grupo de investigación Instituto de Genética Humana |
| dc.contributor.javerianateacher.none.fl_str_mv |
Briceño Balcázar, Ignacio Torres-López, Diana María |
| dc.subject.keyword.spa.fl_str_mv |
Breast cancer Genetic epidemiology Risk prediction Missense variants |
| topic |
Breast cancer Genetic epidemiology Risk prediction Missense variants |
| description |
Q1 |
| publishDate |
2022 |
| dc.date.accessioned.none.fl_str_mv |
2022-10-18T19:14:17Z |
| dc.date.available.none.fl_str_mv |
2022-10-18T19:14:17Z |
| dc.date.created.none.fl_str_mv |
2022-05-18 |
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Artículo de revista |
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http://purl.org/coar/resource_type/c_2df8fbb1 |
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http://purl.org/coar/resource_type/c_2df8fbb1 |
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https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-022-01052-8 |
| dc.identifier.issn.spa.fl_str_mv |
1756-994X |
| dc.identifier.uri.none.fl_str_mv |
http://hdl.handle.net/10554/62117 |
| dc.identifier.doi.spa.fl_str_mv |
https://doi.org/10.1186/s13073-022-01052-8 |
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instname:Pontificia Universidad Javeriana |
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reponame:Repositorio Institucional - Pontificia Universidad Javeriana |
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repourl:https://repository.javeriana.edu.co |
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https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-022-01052-8 http://hdl.handle.net/10554/62117 https://doi.org/10.1186/s13073-022-01052-8 |
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1756-994X instname:Pontificia Universidad Javeriana reponame:Repositorio Institucional - Pontificia Universidad Javeriana repourl:https://repository.javeriana.edu.co |
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eng |
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eng |
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1 |
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17 |
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Genome Medicine |
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14 |
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Atribución-NoComercial 4.0 Internacional |
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http://creativecommons.org/licenses/by-nc/4.0/ |
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Atribución-NoComercial 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc/4.0/http://purl.org/coar/access_right/c_abf2Dorling, LeilaCarvalho, SaraAllen, JamieParsons, Michael T.Fortuno, CristinaGonzález-Neira, AnnaHeijl, Stephan M.Adank, Muriel A.Ahearn, Thomas U.Andrulis, Irene L.Auvinen, PäiviBecher, HeikoBeckmann, Matthias W.Behrens, SabineBermisheva, MarinaBogdanova, Natalia V.Bojesen, Stig E.Bolla, Manjeet K.Bremer, MichaelCamp, Nicola J.Campbell, ArchieCastelao, Jose E.Chang-Claude, JennyChanock, Stephen J.Chenevix-Trench, GeorgiaNBCS CollaboratorsCollée, J. MargrietCzene, KamilaDennis, JoeDörk, ThiloEriksson, MikaelEvans, Gareth D.Fasching, Peter A.Figueroa, JonineFlyger, HenrikGabrielson, MarikeGago-Dominguez, ManuelaGarcía-Closas, MontserratGiles, Graham G.Glendon, GordGuénel, PascalGündert, MelanieHadjisavvas, AndreasHahnen, EricHall, PerHamann, UteHarkness, Elaine F.Hartman, MikaelHogervorst, Frans B. L.Hollestelle, AntoinetteHoppe, ReinerHowell, AnthonykConFab InvestigatorsSGBCC InvestigatorsJakubowska, AnnaJung, AudreyKhusnutdinova, ElzaKim, Sung-WonKo, Yon-DschunKristensen, Vessela N.Lakeman, Inge M. M.Li, JingmeiLindblom, AnnikaLoizidou, Maria A.Lophatananon, ArtitayaLubiński, JanLuccarini, CraigMadsen, Michael J.Mannermaa, ArtoManoochehri, MehdiMargolin, SaraMavroudis, DimitriosMilne, Roger L.Mohd Taib, Nur AishahMuir, KennethNevanlinna, HeliNewman, William G.Oosterwijk, Jan C.Park, Sue K.Peterlongo, PaoloRadice, PaoloSaloustros, EmmanouilSawyer, Elinor J.Schmutzler, Rita K.Shah, MitulSim, XuelingSouthey, Melissa C.Surowy, HaraldSuvanto, MaijaTomlinson, IanTruong, Thérèsevan Asperen, Christi J.Waltes, ReginaWang, QinYang, Xiaohong R.Pharoah, Paul D. P.Schmidt, Marjanka K.Benitez, JavierVroling, BasDunning, Alison M.Teo, Soo HwangKvist, Andersde la Hoya, MiguelDevilee, PeterSpurdle, Amanda B.Vreeswijk, Maaike P.G.Easton, Douglas F.Briceño Balcázar, IgnacioTorres-López, Diana MaríaPontificia Universidad Javeriana. Facultad de Medicina. Instituto de Genética Humana. Grupo de investigación Instituto de Genética HumanaBriceño Balcázar, IgnacioTorres-López, Diana María2022-10-18T19:14:17Z2022-10-18T19:14:17Z2022-05-18https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-022-01052-81756-994Xhttp://hdl.handle.net/10554/62117https://doi.org/10.1186/s13073-022-01052-8instname:Pontificia Universidad Javerianareponame:Repositorio Institucional - Pontificia Universidad Javerianarepourl:https://repository.javeriana.edu.coPDFapplication/pdfengBreast cancer risks associated with missense variants in breast cancer susceptibility genesArtículo de revistahttp://purl.org/coar/resource_type/c_2df8fbb1Q1Q1Background: Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain. Methods: We analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to five in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated. Results: The most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1, and BRCA2, data were compatible with small subsets (approximately 7%, 2%, and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47–2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best fitting models were well calibrated in the validation set. Conclusions: These results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility.https://orcid.org/0000-0001-7300-6401https://orcid.org/0000-0002-9879-9775Revista Internacional - IndexadaA1NoBreast cancerGenetic epidemiologyRisk predictionMissense variants117Genome Medicine14ORIGINALBreast cancer risks associated with missense.pdfBreast cancer risks associated with missense.pdfArtículoapplication/pdf1702370http://repository.javeriana.edu.co/bitstream/10554/62117/1/Breast%20cancer%20risks%20associated%20with%20missense.pdf7c0567fb0a693fbfdd70c827703bd204MD51open accessLICENSElicense.txtlicense.txttext/plain; charset=utf-82603http://repository.javeriana.edu.co/bitstream/10554/62117/2/license.txt2070d280cc89439d983d9eee1b17df53MD52open accessTHUMBNAILBreast cancer risks associated with missense.pdf.jpgBreast cancer risks associated with missense.pdf.jpgIM Thumbnailimage/jpeg8955http://repository.javeriana.edu.co/bitstream/10554/62117/4/Breast%20cancer%20risks%20associated%20with%20missense.pdf.jpgeef485155b472e8649c736a61b719962MD54open access10554/62117oai:repository.javeriana.edu.co:10554/621172023-04-10 15:35:24.135Repositorio Institucional - Pontificia Universidad Javerianarepositorio@javeriana.edu.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 |