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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 principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group
2009
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768437/ https://www.ncbi.nlm.nih.gov/pubmed/19707196 http://dx.doi.org/10.1038/sj.bjc.6605279 |
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| author | Sinilnikova, O M Antoniou, A C Simard, J Healey, S Léoné, M Sinnett, D Spurdle, A B Beesley, J Chen, X Greene, M H Loud, J T Lejbkowicz, F Rennert, G Dishon, S Andrulis, I L Domchek, S M Nathanson, K L Manoukian, S Radice, P Konstantopoulou, I Blanco, I Laborde, A L Durán, M Osorio, A Benitez, J Hamann, U Hogervorst, F B L van Os, T A M Gille, H J P Peock, S Cook, M Luccarini, C Evans, D G Lalloo, F Eeles, R Pichert, G Davidson, R Cole, T Cook, J Paterson, J Brewer, C Hughes, D J Coupier, I Giraud, S Coulet, F Colas, C Soubrier, F Rouleau, E Bièche, I Lidereau, R Demange, L Nogues, C Lynch, H T Schmutzler, R K Versmold, B Engel, C Meindl, A Arnold, N Sutter, C Deissler, H Schaefer, D Froster, U G Aittomäki, K Nevanlinna, H McGuffog, L Easton, D F Chenevix-Trench, G Stoppa-Lyonnet, D |
| author_facet | Sinilnikova, O M Antoniou, A C Simard, J Healey, S Léoné, M Sinnett, D Spurdle, A B Beesley, J Chen, X Greene, M H Loud, J T Lejbkowicz, F Rennert, G Dishon, S Andrulis, I L Domchek, S M Nathanson, K L Manoukian, S Radice, P Konstantopoulou, I Blanco, I Laborde, A L Durán, M Osorio, A Benitez, J Hamann, U Hogervorst, F B L van Os, T A M Gille, H J P Peock, S Cook, M Luccarini, C Evans, D G Lalloo, F Eeles, R Pichert, G Davidson, R Cole, T Cook, J Paterson, J Brewer, C Hughes, D J Coupier, I Giraud, S Coulet, F Colas, C Soubrier, F Rouleau, E Bièche, I Lidereau, R Demange, L Nogues, C Lynch, H T Schmutzler, R K Versmold, B Engel, C Meindl, A Arnold, N Sutter, C Deissler, H Schaefer, D Froster, U G Aittomäki, K Nevanlinna, H McGuffog, L Easton, D F Chenevix-Trench, G Stoppa-Lyonnet, D |
| author_sort | Sinilnikova, O M |
| collection | PubMed |
| 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, P(trend)=0.77; MDM2: HR=0.96, 95%CI: 0.84–1.09, P(trend)=0.54) or for BRCA2 mutation carriers (TP53: HR=0.99, 95%CI: 0.87–1.12, P(trend)=0.83; MDM2: HR=0.98, 95%CI: 0.80–1.21, P(trend)=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. |
| format | Text |
| id | pubmed-2768437 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2009 |
| publisher | Nature Publishing Group |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-27684372010-10-20 The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers Sinilnikova, O M Antoniou, A C Simard, J Healey, S Léoné, M Sinnett, D Spurdle, A B Beesley, J Chen, X Greene, M H Loud, J T Lejbkowicz, F Rennert, G Dishon, S Andrulis, I L Domchek, S M Nathanson, K L Manoukian, S Radice, P Konstantopoulou, I Blanco, I Laborde, A L Durán, M Osorio, A Benitez, J Hamann, U Hogervorst, F B L van Os, T A M Gille, H J P Peock, S Cook, M Luccarini, C Evans, D G Lalloo, F Eeles, R Pichert, G Davidson, R Cole, T Cook, J Paterson, J Brewer, C Hughes, D J Coupier, I Giraud, S Coulet, F Colas, C Soubrier, F Rouleau, E Bièche, I Lidereau, R Demange, L Nogues, C Lynch, H T Schmutzler, R K Versmold, B Engel, C Meindl, A Arnold, N Sutter, C Deissler, H Schaefer, D Froster, U G Aittomäki, K Nevanlinna, H McGuffog, L Easton, D F Chenevix-Trench, G Stoppa-Lyonnet, D Br J Cancer Genetics and Genomics 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, P(trend)=0.77; MDM2: HR=0.96, 95%CI: 0.84–1.09, P(trend)=0.54) or for BRCA2 mutation carriers (TP53: HR=0.99, 95%CI: 0.87–1.12, P(trend)=0.83; MDM2: HR=0.98, 95%CI: 0.80–1.21, P(trend)=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. Nature Publishing Group 2009-10-20 2009-08-25 /pmc/articles/PMC2768437/ /pubmed/19707196 http://dx.doi.org/10.1038/sj.bjc.6605279 Text en Copyright © 2009 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Genetics and Genomics Sinilnikova, O M Antoniou, A C Simard, J Healey, S Léoné, M Sinnett, D Spurdle, A B Beesley, J Chen, X Greene, M H Loud, J T Lejbkowicz, F Rennert, G Dishon, S Andrulis, I L Domchek, S M Nathanson, K L Manoukian, S Radice, P Konstantopoulou, I Blanco, I Laborde, A L Durán, M Osorio, A Benitez, J Hamann, U Hogervorst, F B L van Os, T A M Gille, H J P Peock, S Cook, M Luccarini, C Evans, D G Lalloo, F Eeles, R Pichert, G Davidson, R Cole, T Cook, J Paterson, J Brewer, C Hughes, D J Coupier, I Giraud, S Coulet, F Colas, C Soubrier, F Rouleau, E Bièche, I Lidereau, R Demange, L Nogues, C Lynch, H T Schmutzler, R K Versmold, B Engel, C Meindl, A Arnold, N Sutter, C Deissler, H Schaefer, D Froster, U G Aittomäki, K Nevanlinna, H McGuffog, L Easton, D F Chenevix-Trench, G Stoppa-Lyonnet, D 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 |
| 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_short | The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers |
| title_sort | tp53 arg72pro and mdm2 309g>t polymorphisms are not associated with breast cancer risk in brca1 and brca2 mutation carriers |
| topic | Genetics and Genomics |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768437/ https://www.ncbi.nlm.nih.gov/pubmed/19707196 http://dx.doi.org/10.1038/sj.bjc.6605279 |
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tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT davidsonr tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT colet tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT cookj tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT patersonj tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT brewerc tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT hughesdj tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT coupieri tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT girauds tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT couletf tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT colasc tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT soubrierf tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT rouleaue tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT biechei tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT lidereaur tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT demangel tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT noguesc tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT lynchht tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT schmutzlerrk tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT versmoldb tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT engelc tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT meindla tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT arnoldn tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT sutterc tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT deisslerh tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT schaeferd tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT frosterug tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT aittomakik tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT nevanlinnah tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT mcguffogl tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT eastondf tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT chenevixtrenchg tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers AT stoppalyonnetd tp53arg72proandmdm2309gtpolymorphismsarenotassociatedwithbreastcancerriskinbrca1andbrca2mutationcarriers |