The TP53 Arg72Pro and MDM2 309G > T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers
Por:
Sinilnikova, OM, Antoniou, AC, Simard, J, Healey, S, Leone, M, Sinnett, D, Spurdle, AB, Beesley, J, Chen, X, 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, Duran, 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, Bieche, 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, Aittomaki, K, Nevanlinna, H, McGuffog, L, Easton, DF, Chenevix-Trench, G, Stoppa-Lyonnet, D
Publicada:
13 oct 2009
Resumen:
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. British Journal of Cancer (2009) 101, 1456-1460. doi: 10.1038/sj.bjc.6605279 www.bjcancer.com Published online 25 August 2009 (C) 2009 Cancer Research UK
Filiaciones:
Sinilnikova, OM:
Hosp Civils Lyon Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, F-69373 Lyon, France
Univ Lyon, CNRS, Lab Genet Mol Signalisat & Canc, UMR5201, F-69373 Lyon, France
Antoniou, AC:
Univ Cambridge, Dept Publ Hlth & Primary Care, Genet Epidemiol Unit, Canc Res UK, Cambridge CB1 8RN, England
Simard, J:
CHU Laval, Canc Genom Lab, Canada Res Chair Oncogenet, Quebec City, PQ G1V 4G2, Canada
Univ Laval, Quebec City, PQ G1V 4G2, Canada
Healey, S:
Queensland Inst Med Res, Brisbane, Qld 4029, Australia
Leone, M:
Hosp Civils Lyon Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, F-69373 Lyon, France
Sinnett, D:
Univ Montreal, Dept Pediat, Montreal, PQ H3T 1C5, Canada
CHU St Justine, Res Ctr, Div Hematol Oncol, Montreal, PQ H3T 1C5, Canada
Spurdle, AB:
Queensland Inst Med Res, Brisbane, Qld 4029, Australia
Beesley, J:
Queensland Inst Med Res, Brisbane, Qld 4029, Australia
Chen, X:
Queensland Inst Med Res, Brisbane, Qld 4029, Australia
Greene, MH:
NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD 20852 USA
Loud, JT:
NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD 20852 USA
Lejbkowicz, F:
CHS Natl Canc Control Ctr, IL-34362 Haifa, Israel
Carmel Hosp, Dept Community Med & Epidemiol, IL-34362 Haifa, Israel
Technion Israel Inst Technol, Fac Med, IL-34362 Haifa, Israel
Rennert, G:
CHS Natl Canc Control Ctr, IL-34362 Haifa, Israel
Carmel Hosp, Dept Community Med & Epidemiol, IL-34362 Haifa, Israel
Technion Israel Inst Technol, Fac Med, IL-34362 Haifa, Israel
Dishon, S:
CHS Natl Canc Control Ctr, IL-34362 Haifa, Israel
Carmel Hosp, Dept Community Med & Epidemiol, IL-34362 Haifa, Israel
Technion Israel Inst Technol, Fac Med, IL-34362 Haifa, Israel
Andrulis, IL:
Univ Toronto, Dept Mol Genet, Ontario Canc Genet Network, Toronto, ON M5G 1X5, Canada
Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada
Domchek, SM:
Univ Penn, Sch Med, Dept Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA
Nathanson, KL:
Univ Penn, Sch Med, Dept Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA
Manoukian, S:
Fdn IRCCS Ist Nazl Tumori, Unit Med Genet, Milan, Italy
Radice, P:
Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol, I-20133 Milan, Italy
Fdn Ist FIRC Oncol Mol, IFOM, I-20139 Milan, Italy
Konstantopoulou, I:
NCSR Demokritos, Mol Diagnost Lab, IRRP, Athens 15310, Greece
Blanco, I:
Inst Catala Oncol, Canc Genet Counseling Program, Barcelona 08907, Spain
Laborde, AL:
Hosp Santa Creu i Sant Pau, Serv Genet, Barcelona 08025, Spain
Duran, M:
Univ Valladolid, Inst Mol Biol & Genet, Canc Genet Lab, E-47002 Valladolid, Spain
Osorio, A:
Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Programme, Madrid 28029, Spain
Benitez, J:
Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Programme, Madrid 28029, Spain
Hamann, U:
Deutsch Krebsforschungszentrum, Mol Genet Breast Canc, D-69120 Heidelberg, Germany
Hogervorst, FBL:
Netherlands Canc Inst, Dept Pathol, NL-1066 CX Amsterdam, Netherlands
Netherlands Canc Inst, Family Canc Clin, NL-1066 CX Amsterdam, Netherlands
van Os, TAM:
Univ Amsterdam, Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands
Gille, HJP:
Free Univ Amsterdam, Med Ctr, Dept Clin Mol Genet, NL-1081 HV Amsterdam, Netherlands
Peock, S:
Univ Cambridge, Dept Publ Hlth & Primary Care, Genet Epidemiol Unit, Canc Res UK, Cambridge CB1 8RN, England
Cook, M:
Univ Cambridge, Dept Publ Hlth & Primary Care, Genet Epidemiol Unit, Canc Res UK, Cambridge CB1 8RN, England
Luccarini, C:
Univ Cambridge, Dept Oncol, Cambridge CB1 8RN, England
Evans, DG:
Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester M13 OJH, Lancs, England
Lalloo, F:
Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester M13 OJH, Lancs, England
Eeles, R:
Inst Canc Res, Translat Canc Genet Team, Sutton SM2 5NG, Surrey, England
Royal Marsden NHS Fdn Trust, Sutton SM2 5NG, Surrey, England
Pichert, G:
Guys Hosp, London SE1 9RT, England
Davidson, R:
Ferguson Smith Ctr Clin Genet, Glasgow G3 8SJ, Lanark, Scotland
Cole, T:
Birmingham Womens Hosp Healthcare NHS Trust, W Midlands Reg Genet Serv, Birmingham B15 2TG, W Midlands, England
Cook, J:
Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield S10 2TH, S Yorkshire, England
Paterson, J:
Addenbrookes Hosp, E Anglian Reg Genet Serv, Dept Clin Genet, Cambridge CB2 8QE, England
Brewer, C:
Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England
Hughes, DJ:
Adelaide & Meath Hosp, Trinity Coll, Ctr Hlth Sci, Dept Clin Med, Dublin 24, Ireland
Coupier, I:
CHU Arnaud Villeneuve, Unite Oncogenet, Serv Genet Med, F-34295 Montpellier, France
CRLCC Val Aurelle, Unite Oncogenet, F-34295 Montpellier, France
Giraud, S:
Hosp Civils Lyon Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, F-69373 Lyon, France
Coulet, F:
Univ Paris 06, Grp Hosp Pitie Salpetriere, AP HP, Lab Oncogenet & Angiogenet Mol, F-75651 Paris, France
Colas, C:
Univ Paris 06, Grp Hosp Pitie Salpetriere, AP HP, Lab Oncogenet & Angiogenet Mol, F-75651 Paris, France
Soubrier, F:
Univ Paris 06, Grp Hosp Pitie Salpetriere, AP HP, Lab Oncogenet & Angiogenet Mol, F-75651 Paris, France
Rouleau, E:
Ctr Rene Huguenin, INSERM, Oncogenet U735, F-92210 St Cloud, France
Bieche, I:
Ctr Rene Huguenin, INSERM, Oncogenet U735, F-92210 St Cloud, France
Lidereau, R:
Ctr Rene Huguenin, INSERM, Oncogenet U735, F-92210 St Cloud, France
Demange, L:
Ctr Rene Huguenin, Epidemiol Clin, F-92210 St Cloud, France
Nogues, C:
Ctr Rene Huguenin, Epidemiol Clin, F-92210 St Cloud, France
Lynch, HT:
Creighton Univ, Dept Prevent Med, Omaha, NE 68178 USA
Schmutzler, RK:
Univ Cologne, Dept Obstet & Gynaecol, Ctr Hereditary Breast & Ovarian Canc, D-50924 Cologne, Germany
Versmold, B:
Univ Cologne, Dept Obstet & Gynaecol, Ctr Hereditary Breast & Ovarian Canc, D-50924 Cologne, Germany
Engel, C:
Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04103 Leipzig, Germany
Meindl, A:
Tech Univ Munich, Dept Obstet & Gynaecol, D-80333 Munich, Germany
Arnold, N:
Univ Schleswig Holstein, Dept Obstet & Gynaecol, D-24105 Kiel, Germany
Sutter, C:
Univ Heidelberg, Inst Human Genet, D-69117 Heidelberg, Germany
Deissler, H:
Univ Ulm, Dept Obstet & Gynaecol, D-89069 Ulm, Germany
Schaefer, D:
Goethe Univ Frankfurt, Inst Human Genet, D-60325 Frankfurt, Germany
Froster, UG:
Univ Leipzig, Inst Human Genet, D-04103 Leipzig, Germany
Aittomaki, K:
Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki 00029, Finland
Nevanlinna, H:
Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki 00029, Finland
Easton, DF:
Univ Cambridge, Dept Publ Hlth & Primary Care, Genet Epidemiol Unit, Canc Res UK, Cambridge CB1 8RN, England
Chenevix-Trench, G:
Queensland Inst Med Res, Brisbane, Qld 4029, Australia
Stoppa-Lyonnet, D:
Univ Paris 05, Inst Curie, Serv Genet Oncol, INSERM,U508, F-75248 Paris, France
Green Published, Hybrid Gold, Green Accepted
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