The TP53 Arg72Pro and MDM2 309GT polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers

O. M. Sinilnikova, A. C. Antoniou, J. Simard, S. Healey, M. Léoné, D. Sinnett, A. B. Spurdle, J. Beesley, X. Chen, K. ConFab, M. H. Greene, J. T. Loud, F. Lejbkowicz, G. Rennert, S. Dishon, I. L. Andrulis, S. M. Domchek, K. L. Nathanson, S. Manoukian, P. RadiceI. Konstantopoulou, I. Blanco, A. L. Laborde, M. Durán, A. Osorio, J. Benitez, U. Hamann, F. B L Hogervorst, T. A M Van Os, H. J P Gille, S. Peock, M. Cook, C. Luccarini, D. G. Evans, F. Lalloo, R. Eeles, G. Pichert, R. Davidson, T. Cole, J. Cook, J. Paterson, C. Brewer, D. J. Hughes, I. Coupier, S. Giraud, F. Coulet, C. Colas, F. Soubrier, E. Rouleau, I. Bièche, R. Lidereau, L. Demange, C. Nogues, Henry T. Lynch, R. K. Schmutzler, B. Versmold, C. Engel, A. Meindl, N. Arnold, C. Sutter, H. Deissler, D. Schaefer, U. G. Froster, K. Aittomäki, H. Nevanlinna, L. McGuffog, D. F. Easton, G. Chenevix-Trench, D. Stoppa-Lyonnet

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Abstract

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 (309TG, 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 309TG 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: HR0.96, 95%CI: 0.84-1.09, P trend 0.54) or for BRCA2 mutation carriers (TP53: HR0.99, 95%CI: 0.87-1.12, P trend 0.83; MDM2: HR0.98, 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 309TG, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers.

Original languageEnglish
Pages (from-to)1456-1460
Number of pages5
JournalBritish Journal of Cancer
Volume101
Issue number8
DOIs
StatePublished - Oct 20 2009

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Single Nucleotide Polymorphism
Breast Neoplasms
Mutation
Confidence Intervals
Carcinogenesis
Genotype
Proportional Hazards Models
Genetic Promoter Regions
Alleles
Research Personnel

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

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Sinilnikova, O. M., Antoniou, A. C., Simard, J., Healey, S., Léoné, M., Sinnett, D., ... Stoppa-Lyonnet, D. (2009). The TP53 Arg72Pro and MDM2 309GT polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. British Journal of Cancer, 101(8), 1456-1460. https://doi.org/10.1038/sj.bjc.6605279

The TP53 Arg72Pro and MDM2 309GT 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.; ConFab, K.; 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, Henry 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.

In: British Journal of Cancer, Vol. 101, No. 8, 20.10.2009, p. 1456-1460.

Research output: Contribution to journalArticle

Sinilnikova, OM, Antoniou, AC, Simard, J, Healey, S, Léoné, M, Sinnett, D, Spurdle, AB, Beesley, J, Chen, X, ConFab, K, Greene, MH, Loud, JT, Lejbkowicz, F, Rennert, G, Dishon, S, Andrulis, IL, Domchek, SM, Nathanson, KL, Manoukian, S, Radice, P, Konstantopoulou, I, Blanco, I, Laborde, AL, Durán, M, Osorio, A, Benitez, J, Hamann, U, Hogervorst, FBL, Van Os, TAM, Gille, HJP, Peock, S, Cook, M, Luccarini, C, Evans, DG, Lalloo, F, Eeles, R, Pichert, G, Davidson, R, Cole, T, Cook, J, Paterson, J, Brewer, C, Hughes, DJ, Coupier, I, Giraud, S, Coulet, F, Colas, C, Soubrier, F, Rouleau, E, Bièche, I, Lidereau, R, Demange, L, Nogues, C, Lynch, HT, Schmutzler, RK, Versmold, B, Engel, C, Meindl, A, Arnold, N, Sutter, C, Deissler, H, Schaefer, D, Froster, UG, Aittomäki, K, Nevanlinna, H, McGuffog, L, Easton, DF, Chenevix-Trench, G & Stoppa-Lyonnet, D 2009, 'The TP53 Arg72Pro and MDM2 309GT polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers', British Journal of Cancer, vol. 101, no. 8, pp. 1456-1460. https://doi.org/10.1038/sj.bjc.6605279
Sinilnikova, O. M. ; Antoniou, A. C. ; Simard, J. ; Healey, S. ; Léoné, M. ; Sinnett, D. ; Spurdle, A. B. ; Beesley, J. ; Chen, X. ; ConFab, K. ; 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, Henry 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 309GT polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. In: British Journal of Cancer. 2009 ; Vol. 101, No. 8. pp. 1456-1460.
@article{e2277e6ba4a34621a62aa96dd107dee0,
title = "The TP53 Arg72Pro and MDM2 309GT polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers",
abstract = "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 (309TG, 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 309TG 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: HR0.96, 95{\%}CI: 0.84-1.09, P trend 0.54) or for BRCA2 mutation carriers (TP53: HR0.99, 95{\%}CI: 0.87-1.12, P trend 0.83; MDM2: HR0.98, 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 309TG, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers.",
author = "Sinilnikova, {O. M.} and Antoniou, {A. C.} and J. Simard and S. Healey and M. L{\'e}on{\'e} and D. Sinnett and Spurdle, {A. B.} and J. Beesley and X. Chen and K. ConFab and Greene, {M. H.} and Loud, {J. T.} and F. Lejbkowicz and G. Rennert and S. Dishon and Andrulis, {I. L.} and Domchek, {S. M.} and Nathanson, {K. L.} and S. Manoukian and P. Radice and I. Konstantopoulou and I. Blanco and Laborde, {A. L.} and M. Dur{\'a}n and A. Osorio and J. Benitez and U. Hamann and Hogervorst, {F. B L} and {Van Os}, {T. A M} and Gille, {H. J P} and S. Peock and M. Cook and C. Luccarini and Evans, {D. G.} and F. Lalloo and R. Eeles and G. Pichert and R. Davidson and T. Cole and J. Cook and J. Paterson and C. Brewer and Hughes, {D. J.} and I. Coupier and S. Giraud and F. Coulet and C. Colas and F. Soubrier and E. Rouleau and I. Bi{\`e}che and R. Lidereau and L. Demange and C. Nogues and Lynch, {Henry T.} and Schmutzler, {R. K.} and B. Versmold and C. Engel and A. Meindl and N. Arnold and C. Sutter and H. Deissler and D. Schaefer and Froster, {U. G.} and K. Aittom{\"a}ki and H. Nevanlinna and L. McGuffog and Easton, {D. F.} and G. Chenevix-Trench and D. Stoppa-Lyonnet",
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month = "10",
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doi = "10.1038/sj.bjc.6605279",
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volume = "101",
pages = "1456--1460",
journal = "British Journal of Cancer",
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TY - JOUR

T1 - The TP53 Arg72Pro and MDM2 309GT polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers

AU - Sinilnikova, O. M.

AU - Antoniou, A. C.

AU - Simard, J.

AU - Healey, S.

AU - Léoné, M.

AU - Sinnett, D.

AU - Spurdle, A. B.

AU - Beesley, J.

AU - Chen, X.

AU - ConFab, K.

AU - Greene, M. H.

AU - Loud, J. T.

AU - Lejbkowicz, F.

AU - Rennert, G.

AU - Dishon, S.

AU - Andrulis, I. L.

AU - Domchek, S. M.

AU - Nathanson, K. L.

AU - Manoukian, S.

AU - Radice, P.

AU - Konstantopoulou, I.

AU - Blanco, I.

AU - Laborde, A. L.

AU - Durán, M.

AU - Osorio, A.

AU - Benitez, J.

AU - Hamann, U.

AU - Hogervorst, F. B L

AU - Van Os, T. A M

AU - Gille, H. J P

AU - Peock, S.

AU - Cook, M.

AU - Luccarini, C.

AU - Evans, D. G.

AU - Lalloo, F.

AU - Eeles, R.

AU - Pichert, G.

AU - Davidson, R.

AU - Cole, T.

AU - Cook, J.

AU - Paterson, J.

AU - Brewer, C.

AU - Hughes, D. J.

AU - Coupier, I.

AU - Giraud, S.

AU - Coulet, F.

AU - Colas, C.

AU - Soubrier, F.

AU - Rouleau, E.

AU - Bièche, I.

AU - Lidereau, R.

AU - Demange, L.

AU - Nogues, C.

AU - Lynch, Henry T.

AU - Schmutzler, R. K.

AU - Versmold, B.

AU - Engel, C.

AU - Meindl, A.

AU - Arnold, N.

AU - Sutter, C.

AU - Deissler, H.

AU - Schaefer, D.

AU - Froster, U. G.

AU - Aittomäki, K.

AU - Nevanlinna, H.

AU - McGuffog, L.

AU - Easton, D. F.

AU - Chenevix-Trench, G.

AU - Stoppa-Lyonnet, D.

PY - 2009/10/20

Y1 - 2009/10/20

N2 - 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 (309TG, 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 309TG 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: HR0.96, 95%CI: 0.84-1.09, P trend 0.54) or for BRCA2 mutation carriers (TP53: HR0.99, 95%CI: 0.87-1.12, P trend 0.83; MDM2: HR0.98, 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 309TG, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers.

AB - 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 (309TG, 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 309TG 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: HR0.96, 95%CI: 0.84-1.09, P trend 0.54) or for BRCA2 mutation carriers (TP53: HR0.99, 95%CI: 0.87-1.12, P trend 0.83; MDM2: HR0.98, 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 309TG, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers.

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U2 - 10.1038/sj.bjc.6605279

DO - 10.1038/sj.bjc.6605279

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JF - British Journal of Cancer

SN - 0007-0920

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