The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers
Background: the TP53 pathway, in which TP53 and its negative regulator MDM2 are the central elements, has an important role in carcinogenesis, particularly in BRCA1- and BRCA2-mediated carcinogenesis. A single nucleotide polymorphism (SNP) in the promoter region of MDM2 (309T>G, rs2279744) and a...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2009 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/148042 |
| Acceso en línea: | https://hdl.handle.net/2445/148042 |
| Access Level: | acceso abierto |
| Palabra clave: | Càncer de mama Genètica Mutació (Biologia) Nucleòtids Breast cancer Genetics Mutation (Biology) Nucleotides |
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The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriersSinilnikova, Olga M.Antoniou, Antonis C.Simard, JacquesHealey, SueLéoné, MélanieSinnett, DanielSpurdle, Amanda B.Beesley, JonathanChen, XiengKConFab InvestigatorsGreene, Mark H.Loud, Jennifer T.Lejbkowicz, FlavioRennert, GadDishon, SaraAndrulis, Irene L.OCGN InvestigatorsDomchek, Susan M.Nathanson, Katherine L.Manoukian, SiranoushRadice, PaoloKonstantopoulou, IreneBlanco Guillermo, IgnacioLaborde, Adriana LasaDurán, MercedesOsorio, AnaBenitez, JavierHamann, UteHogervorst, Frans B. L.Van Os, Theo A.Gille, Hans J.P.HEBON InvestigatorsPeock, SusanCook, MargaretLuccarini, CraigEvans, D. GarethLalloo, FionaEeles, Rosalind A.Pichert, GabriellaDavidson, RosemarieCàncer de mamaGenèticaMutació (Biologia)NucleòtidsBreast cancerGeneticsMutation (Biology)NucleotidesBackground: the TP53 pathway, in which TP53 and its negative regulator MDM2 are the central elements, has an important role in carcinogenesis, particularly in BRCA1- and BRCA2-mediated carcinogenesis. A single nucleotide polymorphism (SNP) in the promoter region of MDM2 (309T>G, rs2279744) and a coding SNP of TP53 (Arg72Pro, rs1042522) have been shown to be of functional significance. Methods: to investigate whether these SNPs modify breast cancer risk for BRCA1 and BRCA2 mutation carriers, we pooled genotype data on the TP53 Arg72Pro SNP in 7011 mutation carriers and on the MDM2 309T>G SNP in 2222 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analysed using a Cox proportional hazards model within a retrospective likelihood framework. Results: no association was found between these SNPs and breast cancer risk for BRCA1 (TP53: per-allele hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.93-1.10, Ptrend=0.77; MDM2: HR=0.96, 95%CI: 0.84-1.09, Ptrend=0.54) or for BRCA2 mutation carriers (TP53: HR=0.99, 95%CI: 0.87-1.12, Ptrend=0.83; MDM2: HR=0.98, 95%CI: 0.80-1.21, Ptrend=0.88). We also evaluated the potential combined effects of both SNPs on breast cancer risk, however, none of their combined genotypes showed any evidence of association. Conclusion: there was no evidence that TP53 Arg72Pro or MDM2 309T>G, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers.Cancer Research UK2020202020092020info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion5 p.application/pdfhttps://hdl.handle.net/2445/148042Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1038/sj.bjc.6605279British Journal of Cancer, 2009, vol. 101, num. 8, p. 1456-1460https://doi.org/10.1038/sj.bjc.6605279(c) Sinilnikova, Olga M. et al., 2009info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1480422026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers |
| title |
The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers |
| spellingShingle |
The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers Sinilnikova, Olga M. Càncer de mama Genètica Mutació (Biologia) Nucleòtids Breast cancer Genetics Mutation (Biology) Nucleotides |
| title_short |
The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers |
| title_full |
The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers |
| title_fullStr |
The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers |
| title_full_unstemmed |
The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers |
| title_sort |
The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers |
| dc.creator.none.fl_str_mv |
Sinilnikova, Olga M. Antoniou, Antonis C. Simard, Jacques Healey, Sue Léoné, Mélanie Sinnett, Daniel Spurdle, Amanda B. Beesley, Jonathan Chen, Xieng KConFab Investigators Greene, Mark H. Loud, Jennifer T. Lejbkowicz, Flavio Rennert, Gad Dishon, Sara Andrulis, Irene L. OCGN Investigators Domchek, Susan M. Nathanson, Katherine L. Manoukian, Siranoush Radice, Paolo Konstantopoulou, Irene Blanco Guillermo, Ignacio Laborde, Adriana Lasa Durán, Mercedes Osorio, Ana Benitez, Javier Hamann, Ute Hogervorst, Frans B. L. Van Os, Theo A. Gille, Hans J.P. HEBON Investigators Peock, Susan Cook, Margaret Luccarini, Craig Evans, D. Gareth Lalloo, Fiona Eeles, Rosalind A. Pichert, Gabriella Davidson, Rosemarie |
| author |
Sinilnikova, Olga M. |
| author_facet |
Sinilnikova, Olga M. Antoniou, Antonis C. Simard, Jacques Healey, Sue Léoné, Mélanie Sinnett, Daniel Spurdle, Amanda B. Beesley, Jonathan Chen, Xieng KConFab Investigators Greene, Mark H. Loud, Jennifer T. Lejbkowicz, Flavio Rennert, Gad Dishon, Sara Andrulis, Irene L. OCGN Investigators Domchek, Susan M. Nathanson, Katherine L. Manoukian, Siranoush Radice, Paolo Konstantopoulou, Irene Blanco Guillermo, Ignacio Laborde, Adriana Lasa Durán, Mercedes Osorio, Ana Benitez, Javier Hamann, Ute Hogervorst, Frans B. L. Van Os, Theo A. Gille, Hans J.P. HEBON Investigators Peock, Susan Cook, Margaret Luccarini, Craig Evans, D. Gareth Lalloo, Fiona Eeles, Rosalind A. Pichert, Gabriella Davidson, Rosemarie |
| author_role |
author |
| author2 |
Antoniou, Antonis C. Simard, Jacques Healey, Sue Léoné, Mélanie Sinnett, Daniel Spurdle, Amanda B. Beesley, Jonathan Chen, Xieng KConFab Investigators Greene, Mark H. Loud, Jennifer T. Lejbkowicz, Flavio Rennert, Gad Dishon, Sara Andrulis, Irene L. OCGN Investigators Domchek, Susan M. Nathanson, Katherine L. Manoukian, Siranoush Radice, Paolo Konstantopoulou, Irene Blanco Guillermo, Ignacio Laborde, Adriana Lasa Durán, Mercedes Osorio, Ana Benitez, Javier Hamann, Ute Hogervorst, Frans B. L. Van Os, Theo A. Gille, Hans J.P. HEBON Investigators Peock, Susan Cook, Margaret Luccarini, Craig Evans, D. Gareth Lalloo, Fiona Eeles, Rosalind A. Pichert, Gabriella Davidson, Rosemarie |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Càncer de mama Genètica Mutació (Biologia) Nucleòtids Breast cancer Genetics Mutation (Biology) Nucleotides |
| topic |
Càncer de mama Genètica Mutació (Biologia) Nucleòtids Breast cancer Genetics Mutation (Biology) Nucleotides |
| description |
Background: the TP53 pathway, in which TP53 and its negative regulator MDM2 are the central elements, has an important role in carcinogenesis, particularly in BRCA1- and BRCA2-mediated carcinogenesis. A single nucleotide polymorphism (SNP) in the promoter region of MDM2 (309T>G, rs2279744) and a coding SNP of TP53 (Arg72Pro, rs1042522) have been shown to be of functional significance. Methods: to investigate whether these SNPs modify breast cancer risk for BRCA1 and BRCA2 mutation carriers, we pooled genotype data on the TP53 Arg72Pro SNP in 7011 mutation carriers and on the MDM2 309T>G SNP in 2222 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analysed using a Cox proportional hazards model within a retrospective likelihood framework. Results: no association was found between these SNPs and breast cancer risk for BRCA1 (TP53: per-allele hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.93-1.10, Ptrend=0.77; MDM2: HR=0.96, 95%CI: 0.84-1.09, Ptrend=0.54) or for BRCA2 mutation carriers (TP53: HR=0.99, 95%CI: 0.87-1.12, Ptrend=0.83; MDM2: HR=0.98, 95%CI: 0.80-1.21, Ptrend=0.88). We also evaluated the potential combined effects of both SNPs on breast cancer risk, however, none of their combined genotypes showed any evidence of association. Conclusion: there was no evidence that TP53 Arg72Pro or MDM2 309T>G, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers. |
| publishDate |
2009 |
| dc.date.none.fl_str_mv |
2009 2020 2020 2020 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
| format |
article |
| status_str |
acceptedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/148042 |
| url |
https://hdl.handle.net/2445/148042 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Versió postprint del document publicat a: https://doi.org/10.1038/sj.bjc.6605279 British Journal of Cancer, 2009, vol. 101, num. 8, p. 1456-1460 https://doi.org/10.1038/sj.bjc.6605279 |
| dc.rights.none.fl_str_mv |
(c) Sinilnikova, Olga M. et al., 2009 info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
(c) Sinilnikova, Olga M. et al., 2009 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
5 p. application/pdf |
| dc.publisher.none.fl_str_mv |
Cancer Research UK |
| publisher.none.fl_str_mv |
Cancer Research UK |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Patologia i Terapèutica Experimental) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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1869420397181534208 |
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15.811543 |