The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers
Identifieur interne : 000028 ( Pmc/Corpus ); précédent : 000027; suivant : 000029The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers
Auteurs : O M Sinilnikova ; A C Antoniou ; J. Simard ; S. Healey ; M. Léoné ; D. Sinnett ; A B Spurdle ; J. Beesley ; X. Chen ; M H Greene ; J T Loud ; F. Lejbkowicz ; G. Rennert ; S. Dishon ; I L Andrulis ; S M Domchek ; K L Nathanson ; S. Manoukian ; P. Radice ; I. 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 ; H T Lynch ; R K Schmutzler ; B. Versmold ; C. Engel ; A. Meindl ; N. Arnold ; C. Sutter ; H. Deissler ; D. Schaefer ; U G Froster ; K. Aittom Ki ; H. Nevanlinna ; L. Mcguffog ; D F Easton ; G. Chenevix-Trench ; D. Stoppa-LyonnetSource :
- British Journal of Cancer [ 0007-0920 ] ; 2009.
Abstract
The
To investigate whether these SNPs modify breast cancer risk for
No association was found between these SNPs and breast cancer risk for
There was no evidence that
Url:
DOI: 10.1038/sj.bjc.6605279
PubMed: 19707196
PubMed Central: 2768437
Links to Exploration step
PMC:2768437Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The <italic>TP53</italic> Arg72Pro and <italic>MDM2</italic> 309G>T polymorphisms are not associated with breast cancer risk in <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers</title><author><name sortKey="Sinilnikova, O M" sort="Sinilnikova, O M" uniqKey="Sinilnikova O" first="O M" last="Sinilnikova">O M Sinilnikova</name><affiliation><nlm:aff id="aff1"><institution>Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon / Centre Léon Bérard</institution> Lyon 69373,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>Laboratoire de Génétique Moléculaire, Signalisation et Cancer, UMR5201 CNRS, Université de Lyon</institution> Lyon 69373,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Antoniou, A C" sort="Antoniou, A C" uniqKey="Antoniou A" first="A C" last="Antoniou">A C Antoniou</name><affiliation><nlm:aff id="aff3"><institution>Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge</institution> Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Simard, J" sort="Simard, J" uniqKey="Simard J" first="J" last="Simard">J. Simard</name><affiliation><nlm:aff id="aff4"><institution>Canada Research Chair in Oncogenetics, Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Quebec and Laval University</institution> Quebec,<country>Canada</country> G1V 4G2</nlm:aff></affiliation></author><author><name sortKey="Healey, S" sort="Healey, S" uniqKey="Healey S" first="S" last="Healey">S. Healey</name><affiliation><nlm:aff id="aff5"><institution>Queensland Institute of Medical Research</institution> Brisbane QLD 4029,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Leone, M" sort="Leone, M" uniqKey="Leone M" first="M" last="Léoné">M. Léoné</name><affiliation><nlm:aff id="aff1"><institution>Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon / Centre Léon Bérard</institution> Lyon 69373,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Sinnett, D" sort="Sinnett, D" uniqKey="Sinnett D" first="D" last="Sinnett">D. Sinnett</name><affiliation><nlm:aff id="aff6"><institution>Division of Hematology-Oncology, Research Center, CHU Sainte-Justine</institution> Montreal,<country>Canada</country> H3T 1C5</nlm:aff></affiliation><affiliation><nlm:aff id="aff7"><institution>Department of Pediatrics, University of Montreal</institution> Montreal,<country>Canada</country> H3T 1C5</nlm:aff></affiliation></author><author><name sortKey="Spurdle, A B" sort="Spurdle, A B" uniqKey="Spurdle A" first="A B" last="Spurdle">A B Spurdle</name><affiliation><nlm:aff id="aff5"><institution>Queensland Institute of Medical Research</institution> Brisbane QLD 4029,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Beesley, J" sort="Beesley, J" uniqKey="Beesley J" first="J" last="Beesley">J. Beesley</name><affiliation><nlm:aff id="aff5"><institution>Queensland Institute of Medical Research</institution> Brisbane QLD 4029,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Chen, X" sort="Chen, X" uniqKey="Chen X" first="X" last="Chen">X. Chen</name><affiliation><nlm:aff id="aff5"><institution>Queensland Institute of Medical Research</institution> Brisbane QLD 4029,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Greene, M H" sort="Greene, M H" uniqKey="Greene M" first="M H" last="Greene">M H Greene</name><affiliation><nlm:aff id="aff9"><institution>Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute</institution> Rockville, MD 20852-7231,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Loud, J T" sort="Loud, J T" uniqKey="Loud J" first="J T" last="Loud">J T Loud</name><affiliation><nlm:aff id="aff9"><institution>Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute</institution> Rockville, MD 20852-7231,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Lejbkowicz, F" sort="Lejbkowicz, F" uniqKey="Lejbkowicz F" first="F" last="Lejbkowicz">F. Lejbkowicz</name><affiliation><nlm:aff id="aff10"><institution>CHS National Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and Technion Faculty of Medicine</institution> Haifa 34362,<country>Israel</country></nlm:aff></affiliation></author><author><name sortKey="Rennert, G" sort="Rennert, G" uniqKey="Rennert G" first="G" last="Rennert">G. Rennert</name><affiliation><nlm:aff id="aff10"><institution>CHS National Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and Technion Faculty of Medicine</institution> Haifa 34362,<country>Israel</country></nlm:aff></affiliation></author><author><name sortKey="Dishon, S" sort="Dishon, S" uniqKey="Dishon S" first="S" last="Dishon">S. Dishon</name><affiliation><nlm:aff id="aff10"><institution>CHS National Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and Technion Faculty of Medicine</institution> Haifa 34362,<country>Israel</country></nlm:aff></affiliation></author><author><name sortKey="Andrulis, I L" sort="Andrulis, I L" uniqKey="Andrulis I" first="I L" last="Andrulis">I L Andrulis</name><affiliation><nlm:aff id="aff11"><institution>Ontario Cancer Genetics Network, Cancer Care Ontario, Department of Molecular Genetics, University of Toronto</institution> Toronto, ON,<country>Canada</country> M5G 1X5</nlm:aff></affiliation><affiliation><nlm:aff id="aff12"><institution>Samuel Lunenfeld Research Institute, Mount Sinai Hospital</institution> Toronto, ON,<country>Canada</country> M5G 1X5</nlm:aff></affiliation></author><author><name sortKey="Domchek, S M" sort="Domchek, S M" uniqKey="Domchek S" first="S M" last="Domchek">S M Domchek</name><affiliation><nlm:aff id="aff13"><institution>Department of Medicine, Abramson Cancer Center, University of Pennsylvania School of Medicine</institution> Philadelphia, PA 19104,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Nathanson, K L" sort="Nathanson, K L" uniqKey="Nathanson K" first="K L" last="Nathanson">K L Nathanson</name><affiliation><nlm:aff id="aff13"><institution>Department of Medicine, Abramson Cancer Center, University of Pennsylvania School of Medicine</institution> Philadelphia, PA 19104,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Manoukian, S" sort="Manoukian, S" uniqKey="Manoukian S" first="S" last="Manoukian">S. Manoukian</name><affiliation><nlm:aff id="aff14"><institution>Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumori</institution> Milano,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="Radice, P" sort="Radice, P" uniqKey="Radice P" first="P" last="Radice">P. Radice</name><affiliation><nlm:aff id="aff15"><institution>Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori</institution> Milano 20133,<country>Italy</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff16"><institution>IFOM, Fondazione Istituto FIRC di Oncologia Molecolare</institution> Milano 20139,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="Konstantopoulou, I" sort="Konstantopoulou, I" uniqKey="Konstantopoulou I" first="I" last="Konstantopoulou">I. Konstantopoulou</name><affiliation><nlm:aff id="aff17"><institution>Molecular Diagnostics Laboratory, IRRP, NCSR ‘Demokritos'</institution> 15310 Ag. Paraskevi, Athens,<country>Greece</country></nlm:aff></affiliation></author><author><name sortKey="Blanco, I" sort="Blanco, I" uniqKey="Blanco I" first="I" last="Blanco">I. Blanco</name><affiliation><nlm:aff id="aff18"><institution>Cancer Genetic Counseling Program, Institut Català d'Oncologia</institution> Barcelona 08907,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Laborde, A L" sort="Laborde, A L" uniqKey="Laborde A" first="A L" last="Laborde">A L Laborde</name><affiliation><nlm:aff id="aff19"><institution>Servicio de Genética, Hospital de la Santa Creu i Sant Pau</institution> Barcelona 08025,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Duran, M" sort="Duran, M" uniqKey="Duran M" first="M" last="Durán">M. Durán</name><affiliation><nlm:aff id="aff20"><institution>Laboratorio de Genética del Cáncer, Instituto de Biología y Genética Molecular, Universidad de Valladolid</institution> Valladolid 47002,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Osorio, A" sort="Osorio, A" uniqKey="Osorio A" first="A" last="Osorio">A. Osorio</name><affiliation><nlm:aff id="aff21"><institution>Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO)</institution> Madrid 28029,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Benitez, J" sort="Benitez, J" uniqKey="Benitez J" first="J" last="Benitez">J. Benitez</name><affiliation><nlm:aff id="aff21"><institution>Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO)</institution> Madrid 28029,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Hamann, U" sort="Hamann, U" uniqKey="Hamann U" first="U" last="Hamann">U. Hamann</name><affiliation><nlm:aff id="aff22"><institution>Deutsches Krebsforschungszentrum (DKFZ), Molecular Genetics of Breast Cancer</institution> Heidelberg 69120,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Hogervorst, F B L" sort="Hogervorst, F B L" uniqKey="Hogervorst F" first="F B L" last="Hogervorst">F B L. Hogervorst</name><affiliation><nlm:aff id="aff23"><institution>Department of Pathology and the Family Cancer Clinic, Netherlands Cancer Institute</institution> Amsterdam 1066 CX,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Van Os, T A M" sort="Van Os, T A M" uniqKey="Van Os T" first="T A M" last="Van Os">T A M. Van Os</name><affiliation><nlm:aff id="aff24"><institution>Department of Clinical Genetics, Amsterdam University Medical Centre</institution> Amsterdam 1105 AZ,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Gille, H J P" sort="Gille, H J P" uniqKey="Gille H" first="H J P" last="Gille">H J P. Gille</name><affiliation><nlm:aff id="aff25"><institution>Department of Clinical Molecular Genetics, Free University Medical Centre</institution> Amsterdam 1081 HV,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Peock, S" sort="Peock, S" uniqKey="Peock S" first="S" last="Peock">S. Peock</name><affiliation><nlm:aff id="aff3"><institution>Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge</institution> Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Cook, M" sort="Cook, M" uniqKey="Cook M" first="M" last="Cook">M. Cook</name><affiliation><nlm:aff id="aff3"><institution>Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge</institution> Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Luccarini, C" sort="Luccarini, C" uniqKey="Luccarini C" first="C" last="Luccarini">C. Luccarini</name><affiliation><nlm:aff id="aff26"><institution>Department of Oncology, University of Cambridge</institution> Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Evans, D G" sort="Evans, D G" uniqKey="Evans D" first="D G" last="Evans">D G Evans</name><affiliation><nlm:aff id="aff27"><institution>Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust</institution> Manchester M13 OJH,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Lalloo, F" sort="Lalloo, F" uniqKey="Lalloo F" first="F" last="Lalloo">F. Lalloo</name><affiliation><nlm:aff id="aff27"><institution>Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust</institution> Manchester M13 OJH,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Eeles, R" sort="Eeles, R" uniqKey="Eeles R" first="R" last="Eeles">R. Eeles</name><affiliation><nlm:aff id="aff28"><institution>Translational Cancer Genetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust</institution> Sutton, Surrey SM2 5NG,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Pichert, G" sort="Pichert, G" uniqKey="Pichert G" first="G" last="Pichert">G. Pichert</name><affiliation><nlm:aff id="aff29"><institution>Clinical Genetics, Guy's Hospital</institution> London SE1 9RT,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Davidson, R" sort="Davidson, R" uniqKey="Davidson R" first="R" last="Davidson">R. Davidson</name><affiliation><nlm:aff id="aff30"><institution>Ferguson-Smith Centre for Clinical Genetics</institution> Glasgow G3 8SJ,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Cole, T" sort="Cole, T" uniqKey="Cole T" first="T" last="Cole">T. Cole</name><affiliation><nlm:aff id="aff31"><institution>West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust</institution> Edgbaston, Birmingham B15 2TG,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Cook, J" sort="Cook, J" uniqKey="Cook J" first="J" last="Cook">J. Cook</name><affiliation><nlm:aff id="aff32"><institution>Sheffield Clinical Genetics Service, Sheffield Children's Hospital</institution> Sheffield S10 2TH,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Paterson, J" sort="Paterson, J" uniqKey="Paterson J" first="J" last="Paterson">J. Paterson</name><affiliation><nlm:aff id="aff33"><institution>Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital</institution> Cambridge CB2 8QE,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Brewer, C" sort="Brewer, C" uniqKey="Brewer C" first="C" last="Brewer">C. Brewer</name><affiliation><nlm:aff id="aff34"><institution>Department of Clinical Genetics, Royal Devon & Exeter Hospital</institution> Exeter EX2 5DW,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Hughes, D J" sort="Hughes, D J" uniqKey="Hughes D" first="D J" last="Hughes">D J Hughes</name><affiliation><nlm:aff id="aff35"><institution>Department of Clinical Medicine, Trinity College Centre for Health Sciences, Adelaide & Meath Hospital</institution> Dublin 24,<country>Ireland</country></nlm:aff></affiliation></author><author><name sortKey="Coupier, I" sort="Coupier, I" uniqKey="Coupier I" first="I" last="Coupier">I. Coupier</name><affiliation><nlm:aff id="aff36"><institution>Service de Génétique Médicale, Unité d'Oncogénétique, CHU Arnaud de Villeneuve</institution> Montpellier 34295,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff37"><institution>Unité d'Oncogénétique, CRLCC Val d'Aurelle</institution> Montpellier 34295,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Giraud, S" sort="Giraud, S" uniqKey="Giraud S" first="S" last="Giraud">S. Giraud</name><affiliation><nlm:aff id="aff1"><institution>Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon / Centre Léon Bérard</institution> Lyon 69373,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Coulet, F" sort="Coulet, F" uniqKey="Coulet F" first="F" last="Coulet">F. Coulet</name><affiliation><nlm:aff id="aff38"><institution>Groupe Hospitalier Pitié-Salpêtriére, Assistance Publique-Hopitaux de Paris, Laboratoire d'Oncogénétique et Angiogénétique Moléculaire, Université Pierre et Marie Curie</institution> Paris 75651,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Colas, C" sort="Colas, C" uniqKey="Colas C" first="C" last="Colas">C. Colas</name><affiliation><nlm:aff id="aff38"><institution>Groupe Hospitalier Pitié-Salpêtriére, Assistance Publique-Hopitaux de Paris, Laboratoire d'Oncogénétique et Angiogénétique Moléculaire, Université Pierre et Marie Curie</institution> Paris 75651,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Soubrier, F" sort="Soubrier, F" uniqKey="Soubrier F" first="F" last="Soubrier">F. Soubrier</name><affiliation><nlm:aff id="aff38"><institution>Groupe Hospitalier Pitié-Salpêtriére, Assistance Publique-Hopitaux de Paris, Laboratoire d'Oncogénétique et Angiogénétique Moléculaire, Université Pierre et Marie Curie</institution> Paris 75651,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Rouleau, E" sort="Rouleau, E" uniqKey="Rouleau E" first="E" last="Rouleau">E. Rouleau</name><affiliation><nlm:aff id="aff39"><institution>INSERM U735 / Oncogenetics, Centre René Huguenin</institution> Saint-Cloud 92210,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Bieche, I" sort="Bieche, I" uniqKey="Bieche I" first="I" last="Bièche">I. Bièche</name><affiliation><nlm:aff id="aff39"><institution>INSERM U735 / Oncogenetics, Centre René Huguenin</institution> Saint-Cloud 92210,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Lidereau, R" sort="Lidereau, R" uniqKey="Lidereau R" first="R" last="Lidereau">R. Lidereau</name><affiliation><nlm:aff id="aff39"><institution>INSERM U735 / Oncogenetics, Centre René Huguenin</institution> Saint-Cloud 92210,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Demange, L" sort="Demange, L" uniqKey="Demange L" first="L" last="Demange">L. Demange</name><affiliation><nlm:aff id="aff40"><institution>Epidémiologie Clinique, Oncogénétique, Centre René Huguenin</institution> Saint-Cloud 92210,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Nogues, C" sort="Nogues, C" uniqKey="Nogues C" first="C" last="Nogues">C. Nogues</name><affiliation><nlm:aff id="aff40"><institution>Epidémiologie Clinique, Oncogénétique, Centre René Huguenin</institution> Saint-Cloud 92210,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Lynch, H T" sort="Lynch, H T" uniqKey="Lynch H" first="H T" last="Lynch">H T Lynch</name><affiliation><nlm:aff id="aff41"><institution>Department of Preventive Medicine, Creighton University</institution> Omaha, NE 68178,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Schmutzler, R K" sort="Schmutzler, R K" uniqKey="Schmutzler R" first="R K" last="Schmutzler">R K Schmutzler</name><affiliation><nlm:aff id="aff43"><institution>Centre for hereditary Breast and Ovarian Cancer, Department of Obstetrics and Gynaecology, University of Cologne</institution> Cologne 50924,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Versmold, B" sort="Versmold, B" uniqKey="Versmold B" first="B" last="Versmold">B. Versmold</name><affiliation><nlm:aff id="aff43"><institution>Centre for hereditary Breast and Ovarian Cancer, Department of Obstetrics and Gynaecology, University of Cologne</institution> Cologne 50924,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Engel, C" sort="Engel, C" uniqKey="Engel C" first="C" last="Engel">C. Engel</name><affiliation><nlm:aff id="aff44"><institution>Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig</institution> Leipzig 04103,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Meindl, A" sort="Meindl, A" uniqKey="Meindl A" first="A" last="Meindl">A. Meindl</name><affiliation><nlm:aff id="aff45"><institution>Department of Obstetrics and Gynaecology, Technical University Munich</institution> Munich 80333,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Arnold, N" sort="Arnold, N" uniqKey="Arnold N" first="N" last="Arnold">N. Arnold</name><affiliation><nlm:aff id="aff46"><institution>Department of Obstetrics and Gynaecology, University of Schleswig-Holstein</institution> Kiel 24105,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Sutter, C" sort="Sutter, C" uniqKey="Sutter C" first="C" last="Sutter">C. Sutter</name><affiliation><nlm:aff id="aff47"><institution>Institute of Human Genetics, University of Heidelberg</institution> Heidelberg 69117,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Deissler, H" sort="Deissler, H" uniqKey="Deissler H" first="H" last="Deissler">H. Deissler</name><affiliation><nlm:aff id="aff48"><institution>Department of Obstetrics and Gynaecology, University of Ulm</institution> Ulm 89069,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Schaefer, D" sort="Schaefer, D" uniqKey="Schaefer D" first="D" last="Schaefer">D. Schaefer</name><affiliation><nlm:aff id="aff49"><institution>Institute of Human Genetics, University of Frankfurt</institution> Frankfurt 60325,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Froster, U G" sort="Froster, U G" uniqKey="Froster U" first="U G" last="Froster">U G Froster</name><affiliation><nlm:aff id="aff50"><institution>Institute of Human Genetics, University of Leipzig</institution> Leipzig 04103,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Aittom Ki, K" sort="Aittom Ki, K" uniqKey="Aittom Ki K" first="K" last="Aittom Ki">K. Aittom Ki</name><affiliation><nlm:aff id="aff51"><institution>Department of Clinical Genetics, Helsinki University Central Hospital</institution> Helsinki, 00029 HUS,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Nevanlinna, H" sort="Nevanlinna, H" uniqKey="Nevanlinna H" first="H" last="Nevanlinna">H. Nevanlinna</name><affiliation><nlm:aff id="aff52"><institution>Department of Obstetrics and Gynecology, Helsinki University Central Hospital</institution> Helsinki, 00029 HUS,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Mcguffog, L" sort="Mcguffog, L" uniqKey="Mcguffog L" first="L" last="Mcguffog">L. Mcguffog</name><affiliation><nlm:aff id="aff3"><institution>Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge</institution> Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Easton, D F" sort="Easton, D F" uniqKey="Easton D" first="D F" last="Easton">D F Easton</name><affiliation><nlm:aff id="aff3"><institution>Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge</institution> Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Chenevix Trench, G" sort="Chenevix Trench, G" uniqKey="Chenevix Trench G" first="G" last="Chenevix-Trench">G. Chenevix-Trench</name><affiliation><nlm:aff id="aff5"><institution>Queensland Institute of Medical Research</institution> Brisbane QLD 4029,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Stoppa Lyonnet, D" sort="Stoppa Lyonnet, D" uniqKey="Stoppa Lyonnet D" first="D" last="Stoppa-Lyonnet">D. Stoppa-Lyonnet</name><affiliation><nlm:aff id="aff42"><institution>INSERM U509, Service de Génétique Oncologique, Institut Curie, Université Paris-Descartes</institution> Paris 75248,<country>France</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19707196</idno><idno type="pmc">2768437</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768437</idno><idno type="RBID">PMC:2768437</idno><idno type="doi">10.1038/sj.bjc.6605279</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">000028</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000028</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The <italic>TP53</italic> Arg72Pro and <italic>MDM2</italic> 309G>T polymorphisms are not associated with breast cancer risk in <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers</title><author><name sortKey="Sinilnikova, O M" sort="Sinilnikova, O M" uniqKey="Sinilnikova O" first="O M" last="Sinilnikova">O M Sinilnikova</name><affiliation><nlm:aff id="aff1"><institution>Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon / Centre Léon Bérard</institution> Lyon 69373,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>Laboratoire de Génétique Moléculaire, Signalisation et Cancer, UMR5201 CNRS, Université de Lyon</institution> Lyon 69373,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Antoniou, A C" sort="Antoniou, A C" uniqKey="Antoniou A" first="A C" last="Antoniou">A C Antoniou</name><affiliation><nlm:aff id="aff3"><institution>Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge</institution> Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Simard, J" sort="Simard, J" uniqKey="Simard J" first="J" last="Simard">J. Simard</name><affiliation><nlm:aff id="aff4"><institution>Canada Research Chair in Oncogenetics, Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Quebec and Laval University</institution> Quebec,<country>Canada</country> G1V 4G2</nlm:aff></affiliation></author><author><name sortKey="Healey, S" sort="Healey, S" uniqKey="Healey S" first="S" last="Healey">S. Healey</name><affiliation><nlm:aff id="aff5"><institution>Queensland Institute of Medical Research</institution> Brisbane QLD 4029,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Leone, M" sort="Leone, M" uniqKey="Leone M" first="M" last="Léoné">M. Léoné</name><affiliation><nlm:aff id="aff1"><institution>Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon / Centre Léon Bérard</institution> Lyon 69373,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Sinnett, D" sort="Sinnett, D" uniqKey="Sinnett D" first="D" last="Sinnett">D. Sinnett</name><affiliation><nlm:aff id="aff6"><institution>Division of Hematology-Oncology, Research Center, CHU Sainte-Justine</institution> Montreal,<country>Canada</country> H3T 1C5</nlm:aff></affiliation><affiliation><nlm:aff id="aff7"><institution>Department of Pediatrics, University of Montreal</institution> Montreal,<country>Canada</country> H3T 1C5</nlm:aff></affiliation></author><author><name sortKey="Spurdle, A B" sort="Spurdle, A B" uniqKey="Spurdle A" first="A B" last="Spurdle">A B Spurdle</name><affiliation><nlm:aff id="aff5"><institution>Queensland Institute of Medical Research</institution> Brisbane QLD 4029,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Beesley, J" sort="Beesley, J" uniqKey="Beesley J" first="J" last="Beesley">J. Beesley</name><affiliation><nlm:aff id="aff5"><institution>Queensland Institute of Medical Research</institution> Brisbane QLD 4029,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Chen, X" sort="Chen, X" uniqKey="Chen X" first="X" last="Chen">X. Chen</name><affiliation><nlm:aff id="aff5"><institution>Queensland Institute of Medical Research</institution> Brisbane QLD 4029,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Greene, M H" sort="Greene, M H" uniqKey="Greene M" first="M H" last="Greene">M H Greene</name><affiliation><nlm:aff id="aff9"><institution>Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute</institution> Rockville, MD 20852-7231,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Loud, J T" sort="Loud, J T" uniqKey="Loud J" first="J T" last="Loud">J T Loud</name><affiliation><nlm:aff id="aff9"><institution>Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute</institution> Rockville, MD 20852-7231,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Lejbkowicz, F" sort="Lejbkowicz, F" uniqKey="Lejbkowicz F" first="F" last="Lejbkowicz">F. Lejbkowicz</name><affiliation><nlm:aff id="aff10"><institution>CHS National Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and Technion Faculty of Medicine</institution> Haifa 34362,<country>Israel</country></nlm:aff></affiliation></author><author><name sortKey="Rennert, G" sort="Rennert, G" uniqKey="Rennert G" first="G" last="Rennert">G. Rennert</name><affiliation><nlm:aff id="aff10"><institution>CHS National Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and Technion Faculty of Medicine</institution> Haifa 34362,<country>Israel</country></nlm:aff></affiliation></author><author><name sortKey="Dishon, S" sort="Dishon, S" uniqKey="Dishon S" first="S" last="Dishon">S. Dishon</name><affiliation><nlm:aff id="aff10"><institution>CHS National Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and Technion Faculty of Medicine</institution> Haifa 34362,<country>Israel</country></nlm:aff></affiliation></author><author><name sortKey="Andrulis, I L" sort="Andrulis, I L" uniqKey="Andrulis I" first="I L" last="Andrulis">I L Andrulis</name><affiliation><nlm:aff id="aff11"><institution>Ontario Cancer Genetics Network, Cancer Care Ontario, Department of Molecular Genetics, University of Toronto</institution> Toronto, ON,<country>Canada</country> M5G 1X5</nlm:aff></affiliation><affiliation><nlm:aff id="aff12"><institution>Samuel Lunenfeld Research Institute, Mount Sinai Hospital</institution> Toronto, ON,<country>Canada</country> M5G 1X5</nlm:aff></affiliation></author><author><name sortKey="Domchek, S M" sort="Domchek, S M" uniqKey="Domchek S" first="S M" last="Domchek">S M Domchek</name><affiliation><nlm:aff id="aff13"><institution>Department of Medicine, Abramson Cancer Center, University of Pennsylvania School of Medicine</institution> Philadelphia, PA 19104,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Nathanson, K L" sort="Nathanson, K L" uniqKey="Nathanson K" first="K L" last="Nathanson">K L Nathanson</name><affiliation><nlm:aff id="aff13"><institution>Department of Medicine, Abramson Cancer Center, University of Pennsylvania School of Medicine</institution> Philadelphia, PA 19104,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Manoukian, S" sort="Manoukian, S" uniqKey="Manoukian S" first="S" last="Manoukian">S. Manoukian</name><affiliation><nlm:aff id="aff14"><institution>Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumori</institution> Milano,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="Radice, P" sort="Radice, P" uniqKey="Radice P" first="P" last="Radice">P. Radice</name><affiliation><nlm:aff id="aff15"><institution>Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori</institution> Milano 20133,<country>Italy</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff16"><institution>IFOM, Fondazione Istituto FIRC di Oncologia Molecolare</institution> Milano 20139,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="Konstantopoulou, I" sort="Konstantopoulou, I" uniqKey="Konstantopoulou I" first="I" last="Konstantopoulou">I. Konstantopoulou</name><affiliation><nlm:aff id="aff17"><institution>Molecular Diagnostics Laboratory, IRRP, NCSR ‘Demokritos'</institution> 15310 Ag. Paraskevi, Athens,<country>Greece</country></nlm:aff></affiliation></author><author><name sortKey="Blanco, I" sort="Blanco, I" uniqKey="Blanco I" first="I" last="Blanco">I. Blanco</name><affiliation><nlm:aff id="aff18"><institution>Cancer Genetic Counseling Program, Institut Català d'Oncologia</institution> Barcelona 08907,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Laborde, A L" sort="Laborde, A L" uniqKey="Laborde A" first="A L" last="Laborde">A L Laborde</name><affiliation><nlm:aff id="aff19"><institution>Servicio de Genética, Hospital de la Santa Creu i Sant Pau</institution> Barcelona 08025,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Duran, M" sort="Duran, M" uniqKey="Duran M" first="M" last="Durán">M. Durán</name><affiliation><nlm:aff id="aff20"><institution>Laboratorio de Genética del Cáncer, Instituto de Biología y Genética Molecular, Universidad de Valladolid</institution> Valladolid 47002,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Osorio, A" sort="Osorio, A" uniqKey="Osorio A" first="A" last="Osorio">A. Osorio</name><affiliation><nlm:aff id="aff21"><institution>Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO)</institution> Madrid 28029,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Benitez, J" sort="Benitez, J" uniqKey="Benitez J" first="J" last="Benitez">J. Benitez</name><affiliation><nlm:aff id="aff21"><institution>Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO)</institution> Madrid 28029,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Hamann, U" sort="Hamann, U" uniqKey="Hamann U" first="U" last="Hamann">U. Hamann</name><affiliation><nlm:aff id="aff22"><institution>Deutsches Krebsforschungszentrum (DKFZ), Molecular Genetics of Breast Cancer</institution> Heidelberg 69120,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Hogervorst, F B L" sort="Hogervorst, F B L" uniqKey="Hogervorst F" first="F B L" last="Hogervorst">F B L. Hogervorst</name><affiliation><nlm:aff id="aff23"><institution>Department of Pathology and the Family Cancer Clinic, Netherlands Cancer Institute</institution> Amsterdam 1066 CX,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Van Os, T A M" sort="Van Os, T A M" uniqKey="Van Os T" first="T A M" last="Van Os">T A M. Van Os</name><affiliation><nlm:aff id="aff24"><institution>Department of Clinical Genetics, Amsterdam University Medical Centre</institution> Amsterdam 1105 AZ,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Gille, H J P" sort="Gille, H J P" uniqKey="Gille H" first="H J P" last="Gille">H J P. Gille</name><affiliation><nlm:aff id="aff25"><institution>Department of Clinical Molecular Genetics, Free University Medical Centre</institution> Amsterdam 1081 HV,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Peock, S" sort="Peock, S" uniqKey="Peock S" first="S" last="Peock">S. Peock</name><affiliation><nlm:aff id="aff3"><institution>Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge</institution> Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Cook, M" sort="Cook, M" uniqKey="Cook M" first="M" last="Cook">M. Cook</name><affiliation><nlm:aff id="aff3"><institution>Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge</institution> Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Luccarini, C" sort="Luccarini, C" uniqKey="Luccarini C" first="C" last="Luccarini">C. Luccarini</name><affiliation><nlm:aff id="aff26"><institution>Department of Oncology, University of Cambridge</institution> Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Evans, D G" sort="Evans, D G" uniqKey="Evans D" first="D G" last="Evans">D G Evans</name><affiliation><nlm:aff id="aff27"><institution>Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust</institution> Manchester M13 OJH,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Lalloo, F" sort="Lalloo, F" uniqKey="Lalloo F" first="F" last="Lalloo">F. Lalloo</name><affiliation><nlm:aff id="aff27"><institution>Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust</institution> Manchester M13 OJH,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Eeles, R" sort="Eeles, R" uniqKey="Eeles R" first="R" last="Eeles">R. Eeles</name><affiliation><nlm:aff id="aff28"><institution>Translational Cancer Genetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust</institution> Sutton, Surrey SM2 5NG,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Pichert, G" sort="Pichert, G" uniqKey="Pichert G" first="G" last="Pichert">G. Pichert</name><affiliation><nlm:aff id="aff29"><institution>Clinical Genetics, Guy's Hospital</institution> London SE1 9RT,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Davidson, R" sort="Davidson, R" uniqKey="Davidson R" first="R" last="Davidson">R. Davidson</name><affiliation><nlm:aff id="aff30"><institution>Ferguson-Smith Centre for Clinical Genetics</institution> Glasgow G3 8SJ,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Cole, T" sort="Cole, T" uniqKey="Cole T" first="T" last="Cole">T. Cole</name><affiliation><nlm:aff id="aff31"><institution>West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust</institution> Edgbaston, Birmingham B15 2TG,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Cook, J" sort="Cook, J" uniqKey="Cook J" first="J" last="Cook">J. Cook</name><affiliation><nlm:aff id="aff32"><institution>Sheffield Clinical Genetics Service, Sheffield Children's Hospital</institution> Sheffield S10 2TH,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Paterson, J" sort="Paterson, J" uniqKey="Paterson J" first="J" last="Paterson">J. Paterson</name><affiliation><nlm:aff id="aff33"><institution>Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital</institution> Cambridge CB2 8QE,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Brewer, C" sort="Brewer, C" uniqKey="Brewer C" first="C" last="Brewer">C. Brewer</name><affiliation><nlm:aff id="aff34"><institution>Department of Clinical Genetics, Royal Devon & Exeter Hospital</institution> Exeter EX2 5DW,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Hughes, D J" sort="Hughes, D J" uniqKey="Hughes D" first="D J" last="Hughes">D J Hughes</name><affiliation><nlm:aff id="aff35"><institution>Department of Clinical Medicine, Trinity College Centre for Health Sciences, Adelaide & Meath Hospital</institution> Dublin 24,<country>Ireland</country></nlm:aff></affiliation></author><author><name sortKey="Coupier, I" sort="Coupier, I" uniqKey="Coupier I" first="I" last="Coupier">I. Coupier</name><affiliation><nlm:aff id="aff36"><institution>Service de Génétique Médicale, Unité d'Oncogénétique, CHU Arnaud de Villeneuve</institution> Montpellier 34295,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff37"><institution>Unité d'Oncogénétique, CRLCC Val d'Aurelle</institution> Montpellier 34295,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Giraud, S" sort="Giraud, S" uniqKey="Giraud S" first="S" last="Giraud">S. Giraud</name><affiliation><nlm:aff id="aff1"><institution>Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon / Centre Léon Bérard</institution> Lyon 69373,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Coulet, F" sort="Coulet, F" uniqKey="Coulet F" first="F" last="Coulet">F. Coulet</name><affiliation><nlm:aff id="aff38"><institution>Groupe Hospitalier Pitié-Salpêtriére, Assistance Publique-Hopitaux de Paris, Laboratoire d'Oncogénétique et Angiogénétique Moléculaire, Université Pierre et Marie Curie</institution> Paris 75651,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Colas, C" sort="Colas, C" uniqKey="Colas C" first="C" last="Colas">C. Colas</name><affiliation><nlm:aff id="aff38"><institution>Groupe Hospitalier Pitié-Salpêtriére, Assistance Publique-Hopitaux de Paris, Laboratoire d'Oncogénétique et Angiogénétique Moléculaire, Université Pierre et Marie Curie</institution> Paris 75651,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Soubrier, F" sort="Soubrier, F" uniqKey="Soubrier F" first="F" last="Soubrier">F. Soubrier</name><affiliation><nlm:aff id="aff38"><institution>Groupe Hospitalier Pitié-Salpêtriére, Assistance Publique-Hopitaux de Paris, Laboratoire d'Oncogénétique et Angiogénétique Moléculaire, Université Pierre et Marie Curie</institution> Paris 75651,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Rouleau, E" sort="Rouleau, E" uniqKey="Rouleau E" first="E" last="Rouleau">E. Rouleau</name><affiliation><nlm:aff id="aff39"><institution>INSERM U735 / Oncogenetics, Centre René Huguenin</institution> Saint-Cloud 92210,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Bieche, I" sort="Bieche, I" uniqKey="Bieche I" first="I" last="Bièche">I. Bièche</name><affiliation><nlm:aff id="aff39"><institution>INSERM U735 / Oncogenetics, Centre René Huguenin</institution> Saint-Cloud 92210,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Lidereau, R" sort="Lidereau, R" uniqKey="Lidereau R" first="R" last="Lidereau">R. Lidereau</name><affiliation><nlm:aff id="aff39"><institution>INSERM U735 / Oncogenetics, Centre René Huguenin</institution> Saint-Cloud 92210,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Demange, L" sort="Demange, L" uniqKey="Demange L" first="L" last="Demange">L. Demange</name><affiliation><nlm:aff id="aff40"><institution>Epidémiologie Clinique, Oncogénétique, Centre René Huguenin</institution> Saint-Cloud 92210,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Nogues, C" sort="Nogues, C" uniqKey="Nogues C" first="C" last="Nogues">C. Nogues</name><affiliation><nlm:aff id="aff40"><institution>Epidémiologie Clinique, Oncogénétique, Centre René Huguenin</institution> Saint-Cloud 92210,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Lynch, H T" sort="Lynch, H T" uniqKey="Lynch H" first="H T" last="Lynch">H T Lynch</name><affiliation><nlm:aff id="aff41"><institution>Department of Preventive Medicine, Creighton University</institution> Omaha, NE 68178,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Schmutzler, R K" sort="Schmutzler, R K" uniqKey="Schmutzler R" first="R K" last="Schmutzler">R K Schmutzler</name><affiliation><nlm:aff id="aff43"><institution>Centre for hereditary Breast and Ovarian Cancer, Department of Obstetrics and Gynaecology, University of Cologne</institution> Cologne 50924,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Versmold, B" sort="Versmold, B" uniqKey="Versmold B" first="B" last="Versmold">B. Versmold</name><affiliation><nlm:aff id="aff43"><institution>Centre for hereditary Breast and Ovarian Cancer, Department of Obstetrics and Gynaecology, University of Cologne</institution> Cologne 50924,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Engel, C" sort="Engel, C" uniqKey="Engel C" first="C" last="Engel">C. Engel</name><affiliation><nlm:aff id="aff44"><institution>Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig</institution> Leipzig 04103,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Meindl, A" sort="Meindl, A" uniqKey="Meindl A" first="A" last="Meindl">A. Meindl</name><affiliation><nlm:aff id="aff45"><institution>Department of Obstetrics and Gynaecology, Technical University Munich</institution> Munich 80333,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Arnold, N" sort="Arnold, N" uniqKey="Arnold N" first="N" last="Arnold">N. Arnold</name><affiliation><nlm:aff id="aff46"><institution>Department of Obstetrics and Gynaecology, University of Schleswig-Holstein</institution> Kiel 24105,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Sutter, C" sort="Sutter, C" uniqKey="Sutter C" first="C" last="Sutter">C. Sutter</name><affiliation><nlm:aff id="aff47"><institution>Institute of Human Genetics, University of Heidelberg</institution> Heidelberg 69117,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Deissler, H" sort="Deissler, H" uniqKey="Deissler H" first="H" last="Deissler">H. Deissler</name><affiliation><nlm:aff id="aff48"><institution>Department of Obstetrics and Gynaecology, University of Ulm</institution> Ulm 89069,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Schaefer, D" sort="Schaefer, D" uniqKey="Schaefer D" first="D" last="Schaefer">D. Schaefer</name><affiliation><nlm:aff id="aff49"><institution>Institute of Human Genetics, University of Frankfurt</institution> Frankfurt 60325,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Froster, U G" sort="Froster, U G" uniqKey="Froster U" first="U G" last="Froster">U G Froster</name><affiliation><nlm:aff id="aff50"><institution>Institute of Human Genetics, University of Leipzig</institution> Leipzig 04103,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Aittom Ki, K" sort="Aittom Ki, K" uniqKey="Aittom Ki K" first="K" last="Aittom Ki">K. Aittom Ki</name><affiliation><nlm:aff id="aff51"><institution>Department of Clinical Genetics, Helsinki University Central Hospital</institution> Helsinki, 00029 HUS,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Nevanlinna, H" sort="Nevanlinna, H" uniqKey="Nevanlinna H" first="H" last="Nevanlinna">H. Nevanlinna</name><affiliation><nlm:aff id="aff52"><institution>Department of Obstetrics and Gynecology, Helsinki University Central Hospital</institution> Helsinki, 00029 HUS,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Mcguffog, L" sort="Mcguffog, L" uniqKey="Mcguffog L" first="L" last="Mcguffog">L. Mcguffog</name><affiliation><nlm:aff id="aff3"><institution>Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge</institution> Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Easton, D F" sort="Easton, D F" uniqKey="Easton D" first="D F" last="Easton">D F Easton</name><affiliation><nlm:aff id="aff3"><institution>Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge</institution> Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Chenevix Trench, G" sort="Chenevix Trench, G" uniqKey="Chenevix Trench G" first="G" last="Chenevix-Trench">G. Chenevix-Trench</name><affiliation><nlm:aff id="aff5"><institution>Queensland Institute of Medical Research</institution> Brisbane QLD 4029,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Stoppa Lyonnet, D" sort="Stoppa Lyonnet, D" uniqKey="Stoppa Lyonnet D" first="D" last="Stoppa-Lyonnet">D. Stoppa-Lyonnet</name><affiliation><nlm:aff id="aff42"><institution>INSERM U509, Service de Génétique Oncologique, Institut Curie, Université Paris-Descartes</institution> Paris 75248,<country>France</country></nlm:aff></affiliation></author></analytic><series><title level="j">British Journal of Cancer</title><idno type="ISSN">0007-0920</idno><idno type="eISSN">1532-1827</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background:</title><p>The <italic>TP53</italic> pathway, in which <italic>TP53</italic> and its negative regulator <italic>MDM2</italic> are the central elements, has an important role in carcinogenesis, particularly in <italic>BRCA1-</italic> and <italic>BRCA2-</italic>mediated carcinogenesis. A single nucleotide polymorphism (SNP) in the promoter region of <italic>MDM2</italic> (309T>G, rs2279744) and a coding SNP of <italic>TP53</italic> (Arg72Pro, rs1042522) have been shown to be of functional significance.</p></sec><sec><title>Methods:</title><p>To investigate whether these SNPs modify breast cancer risk for <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers, we pooled genotype data on the <italic>TP53</italic> Arg72Pro SNP in 7011 mutation carriers and on the <italic>MDM2</italic> 309T>G SNP in 2222 mutation carriers from the Consortium of Investigators of Modifiers of <italic>BRCA1/2</italic> (CIMBA). Data were analysed using a Cox proportional hazards model within a retrospective likelihood framework.</p></sec><sec><title>Results:</title><p>No association was found between these SNPs and breast cancer risk for <italic>BRCA1</italic> (<italic>TP53</italic>: per-allele hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.93–1.10, <italic>P</italic><sub>trend</sub>=0.77; <italic>MDM2</italic>: HR=0.96, 95%CI: 0.84–1.09, <italic>P</italic><sub>trend</sub>=0.54) or for <italic>BRCA2</italic> mutation carriers (<italic>TP53</italic>: HR=0.99, 95%CI: 0.87–1.12, <italic>P</italic><sub>trend</sub>=0.83; <italic>MDM2</italic>: HR=0.98, 95%CI: 0.80–1.21, <italic>P</italic><sub>trend</sub>=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.</p></sec><sec><title>Conclusion:</title><p>There was no evidence that <italic>TP53</italic> Arg72Pro or <italic>MDM2</italic> 309T>G, either singly or in combination, influence breast cancer risk in <italic>BRCA1</italic> or <italic>BRCA2</italic> mutation carriers.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><pmc article-type="other"><pmc-dir>properties open_access</pmc-dir>
<pmc-comment> Original-type: gg</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Br J Cancer</journal-id><journal-title>British Journal of Cancer</journal-title><issn pub-type="ppub">0007-0920</issn><issn pub-type="epub">1532-1827</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">19707196</article-id><article-id pub-id-type="pmc">2768437</article-id><article-id pub-id-type="pii">6605279</article-id><article-id pub-id-type="doi">10.1038/sj.bjc.6605279</article-id><article-categories><subj-group subj-group-type="heading"><subject>Genetics and Genomics</subject></subj-group></article-categories><title-group><article-title>The <italic>TP53</italic> Arg72Pro and <italic>MDM2</italic> 309G>T polymorphisms are not associated with breast cancer risk in <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers</article-title></title-group><contrib-group><contrib 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8RN,<country>UK</country></aff><aff id="aff4"><label>4</label><institution>Canada Research Chair in Oncogenetics, Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Quebec and Laval University</institution> Quebec,<country>Canada</country> G1V 4G2</aff><aff id="aff5"><label>5</label><institution>Queensland Institute of Medical Research</institution> Brisbane QLD 4029,<country>Australia</country></aff><aff id="aff6"><label>6</label><institution>Division of Hematology-Oncology, Research Center, CHU Sainte-Justine</institution> Montreal,<country>Canada</country> H3T 1C5</aff><aff id="aff7"><label>7</label><institution>Department of Pediatrics, University of Montreal</institution> Montreal,<country>Canada</country> H3T 1C5</aff><aff id="aff8"><label>8</label><institution>Peter MacCallum Cancer Center</institution> Melbourne, VIC 3002,<country>Australia</country></aff><aff id="aff9"><label>9</label><institution>Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute</institution> Rockville, MD 20852-7231,<country>USA</country></aff><aff id="aff10"><label>10</label><institution>CHS National Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and Technion Faculty of Medicine</institution> Haifa 34362,<country>Israel</country></aff><aff id="aff11"><label>11</label><institution>Ontario Cancer Genetics Network, Cancer Care Ontario, Department of Molecular Genetics, University of Toronto</institution> Toronto, ON,<country>Canada</country> M5G 1X5</aff><aff id="aff12"><label>12</label><institution>Samuel Lunenfeld Research Institute, Mount Sinai Hospital</institution> Toronto, ON,<country>Canada</country> M5G 1X5</aff><aff id="aff13"><label>13</label><institution>Department of Medicine, Abramson Cancer Center, University of Pennsylvania School of Medicine</institution> Philadelphia, PA 19104,<country>USA</country></aff><aff id="aff14"><label>14</label><institution>Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumori</institution> Milano,<country>Italy</country></aff><aff id="aff15"><label>15</label><institution>Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori</institution> Milano 20133,<country>Italy</country></aff><aff id="aff16"><label>16</label><institution>IFOM, Fondazione Istituto FIRC di Oncologia Molecolare</institution> Milano 20139,<country>Italy</country></aff><aff id="aff17"><label>17</label><institution>Molecular Diagnostics Laboratory, IRRP, NCSR ‘Demokritos'</institution> 15310 Ag. Paraskevi, Athens,<country>Greece</country></aff><aff id="aff18"><label>18</label><institution>Cancer Genetic Counseling Program, Institut Català d'Oncologia</institution> Barcelona 08907,<country>Spain</country></aff><aff id="aff19"><label>19</label><institution>Servicio de Genética, Hospital de la Santa Creu i Sant Pau</institution> Barcelona 08025,<country>Spain</country></aff><aff id="aff20"><label>20</label><institution>Laboratorio de Genética del Cáncer, Instituto de Biología y Genética Molecular, Universidad de Valladolid</institution> Valladolid 47002,<country>Spain</country></aff><aff id="aff21"><label>21</label><institution>Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO)</institution> Madrid 28029,<country>Spain</country></aff><aff id="aff22"><label>22</label><institution>Deutsches Krebsforschungszentrum (DKFZ), Molecular Genetics of Breast Cancer</institution> Heidelberg 69120,<country>Germany</country></aff><aff id="aff23"><label>23</label><institution>Department of Pathology and the Family Cancer Clinic, Netherlands Cancer Institute</institution> Amsterdam 1066 CX,<country>The Netherlands</country></aff><aff id="aff24"><label>24</label><institution>Department of Clinical Genetics, Amsterdam University Medical Centre</institution> Amsterdam 1105 AZ,<country>The Netherlands</country></aff><aff id="aff25"><label>25</label><institution>Department of Clinical Molecular Genetics, Free University Medical Centre</institution> Amsterdam 1081 HV,<country>The Netherlands</country></aff><aff id="aff26"><label>26</label><institution>Department of Oncology, University of Cambridge</institution> Cambridge CB1 8RN,<country>UK</country></aff><aff id="aff27"><label>27</label><institution>Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust</institution> Manchester M13 OJH,<country>UK</country></aff><aff id="aff28"><label>28</label><institution>Translational Cancer Genetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust</institution> Sutton, Surrey SM2 5NG,<country>UK</country></aff><aff id="aff29"><label>29</label><institution>Clinical Genetics, Guy's Hospital</institution> London SE1 9RT,<country>UK</country></aff><aff id="aff30"><label>30</label><institution>Ferguson-Smith Centre for Clinical Genetics</institution> Glasgow G3 8SJ,<country>UK</country></aff><aff id="aff31"><label>31</label><institution>West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust</institution> Edgbaston, Birmingham B15 2TG,<country>UK</country></aff><aff id="aff32"><label>32</label><institution>Sheffield Clinical Genetics Service, Sheffield Children's Hospital</institution> Sheffield S10 2TH,<country>UK</country></aff><aff id="aff33"><label>33</label><institution>Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital</institution> Cambridge CB2 8QE,<country>UK</country></aff><aff id="aff34"><label>34</label><institution>Department of Clinical Genetics, Royal Devon & Exeter Hospital</institution> Exeter EX2 5DW,<country>UK</country></aff><aff id="aff35"><label>35</label><institution>Department of Clinical Medicine, Trinity College Centre for Health Sciences, Adelaide & Meath Hospital</institution> Dublin 24,<country>Ireland</country></aff><aff id="aff36"><label>36</label><institution>Service de Génétique Médicale, Unité d'Oncogénétique, CHU Arnaud de Villeneuve</institution> Montpellier 34295,<country>France</country></aff><aff id="aff37"><label>37</label><institution>Unité d'Oncogénétique, CRLCC Val d'Aurelle</institution> Montpellier 34295,<country>France</country></aff><aff id="aff38"><label>38</label><institution>Groupe Hospitalier Pitié-Salpêtriére, Assistance Publique-Hopitaux de Paris, Laboratoire d'Oncogénétique et Angiogénétique Moléculaire, Université Pierre et Marie Curie</institution> Paris 75651,<country>France</country></aff><aff id="aff39"><label>39</label><institution>INSERM U735 / Oncogenetics, Centre René Huguenin</institution> Saint-Cloud 92210,<country>France</country></aff><aff id="aff40"><label>40</label><institution>Epidémiologie Clinique, Oncogénétique, Centre René Huguenin</institution> Saint-Cloud 92210,<country>France</country></aff><aff id="aff41"><label>41</label><institution>Department of Preventive Medicine, Creighton University</institution> Omaha, NE 68178,<country>USA</country></aff><aff id="aff42"><label>42</label><institution>INSERM U509, Service de Génétique Oncologique, Institut Curie, Université Paris-Descartes</institution> Paris 75248,<country>France</country></aff><aff id="aff43"><label>43</label><institution>Centre for hereditary Breast and Ovarian Cancer, Department of Obstetrics and Gynaecology, University of Cologne</institution> Cologne 50924,<country>Germany</country></aff><aff id="aff44"><label>44</label><institution>Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig</institution> Leipzig 04103,<country>Germany</country></aff><aff id="aff45"><label>45</label><institution>Department of Obstetrics and Gynaecology, Technical University Munich</institution> Munich 80333,<country>Germany</country></aff><aff id="aff46"><label>46</label><institution>Department of Obstetrics and Gynaecology, University of Schleswig-Holstein</institution> Kiel 24105,<country>Germany</country></aff><aff id="aff47"><label>47</label><institution>Institute of Human Genetics, University of Heidelberg</institution> Heidelberg 69117,<country>Germany</country></aff><aff id="aff48"><label>48</label><institution>Department of Obstetrics and Gynaecology, University of Ulm</institution> Ulm 89069,<country>Germany</country></aff><aff id="aff49"><label>49</label><institution>Institute of Human Genetics, University of Frankfurt</institution> Frankfurt 60325,<country>Germany</country></aff><aff id="aff50"><label>50</label><institution>Institute of Human Genetics, University of Leipzig</institution> Leipzig 04103,<country>Germany</country></aff><aff id="aff51"><label>51</label><institution>Department of Clinical Genetics, Helsinki University Central Hospital</institution> Helsinki, 00029 HUS,<country>Finland</country></aff><aff id="aff52"><label>52</label><institution>Department of Obstetrics and Gynecology, Helsinki University Central Hospital</institution> Helsinki, 00029 HUS,<country>Finland</country></aff><author-notes><corresp id="caf1"><label>*</label>Author for correspondence: <email xlink:href="mailto:sinilnik@lyon.fnclcc.fr">sinilnik@lyon.fnclcc.fr</email></corresp></author-notes><pub-date pub-type="epub"><day>25</day><month>08</month><year>2009</year></pub-date><pub-date pub-type="collection"><day>13</day><month>10</month><year>2009</year></pub-date><pub-date pub-type="ppub"><day>20</day><month>10</month><year>2009</year></pub-date><volume>101</volume><issue>8</issue><fpage>1456</fpage><lpage>1460</lpage><history><date date-type="received"><day>17</day><month>04</month><year>2009</year></date><date date-type="rev-recd"><day>15</day><month>07</month><year>2009</year></date><date date-type="accepted"><day>27</day><month>07</month><year>2009</year></date></history><copyright-statement>Copyright 2009, Cancer Research UK</copyright-statement><copyright-year>2009</copyright-year><permissions><copyright-holder>Cancer Research UK</copyright-holder></permissions><abstract><sec><title>Background:</title><p>The <italic>TP53</italic> pathway, in which <italic>TP53</italic> and its negative regulator <italic>MDM2</italic> are the central elements, has an important role in carcinogenesis, particularly in <italic>BRCA1-</italic> and <italic>BRCA2-</italic>mediated carcinogenesis. A single nucleotide polymorphism (SNP) in the promoter region of <italic>MDM2</italic> (309T>G, rs2279744) and a coding SNP of <italic>TP53</italic> (Arg72Pro, rs1042522) have been shown to be of functional significance.</p></sec><sec><title>Methods:</title><p>To investigate whether these SNPs modify breast cancer risk for <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers, we pooled genotype data on the <italic>TP53</italic> Arg72Pro SNP in 7011 mutation carriers and on the <italic>MDM2</italic> 309T>G SNP in 2222 mutation carriers from the Consortium of Investigators of Modifiers of <italic>BRCA1/2</italic> (CIMBA). Data were analysed using a Cox proportional hazards model within a retrospective likelihood framework.</p></sec><sec><title>Results:</title><p>No association was found between these SNPs and breast cancer risk for <italic>BRCA1</italic> (<italic>TP53</italic>: per-allele hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.93–1.10, <italic>P</italic><sub>trend</sub>=0.77; <italic>MDM2</italic>: HR=0.96, 95%CI: 0.84–1.09, <italic>P</italic><sub>trend</sub>=0.54) or for <italic>BRCA2</italic> mutation carriers (<italic>TP53</italic>: HR=0.99, 95%CI: 0.87–1.12, <italic>P</italic><sub>trend</sub>=0.83; <italic>MDM2</italic>: HR=0.98, 95%CI: 0.80–1.21, <italic>P</italic><sub>trend</sub>=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.</p></sec><sec><title>Conclusion:</title><p>There was no evidence that <italic>TP53</italic> Arg72Pro or <italic>MDM2</italic> 309T>G, either singly or in combination, influence breast cancer risk in <italic>BRCA1</italic> or <italic>BRCA2</italic> mutation carriers.</p></sec></abstract><kwd-group><kwd><italic>TP53</italic></kwd><kwd><italic>MDM2</italic></kwd><kwd><italic>BRCA1/2</italic></kwd><kwd>breast cancer</kwd><kwd>polymorphism</kwd><kwd>risk</kwd></kwd-group></article-meta></front><body><p>The <italic>TP53</italic> pathway is crucial for tumour suppression, acting through regulation of cell-cycle control, apoptosis, senescence and DNA repair. The <italic>TP53</italic> gene and its negative regulator <italic>MDM2</italic> are central to this pathway, promoting polyubiquitination and degradation of TP53, and also controlling the TP53 synthesis (<xref ref-type="other" rid="bib19">Toledo and Wahl, 2006</xref>; <xref ref-type="other" rid="bib5">Candeias <italic>et al</italic>, 2008</xref>). Inactivation of the <italic>TP53</italic> pathway has an important role in <italic>BRCA1</italic>- and <italic>BRCA2</italic>-associated tumourigenesis. <italic>BRCA1</italic> and <italic>BRCA2</italic> mutations are associated with genomic instability caused by defective cell-cycle checkpoint and DNA damage repair (<xref ref-type="other" rid="bib8">Deng, 2006</xref>). Mouse model studies have highlighted functional links between these genes. Biallelic inactivation of <italic>BRCA1</italic> and <italic>BRCA2</italic> in mice have shown that embryonic lethality because of growth retardation can be partially rescued in a <italic>Trp53</italic> null background (<xref ref-type="other" rid="bib10">Evers and Jonkers, 2006</xref>). The development of mammary tumours in conditional <italic>BRCA1</italic> and <italic>BRCA2</italic> knockout mice was considerably accelerated in a <italic>Trp53</italic> knockout background (<xref ref-type="other" rid="bib10">Evers and Jonkers, 2006</xref>). In addition, a high incidence of <italic>TP53</italic> mutations has been found in breast tumours of human <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers (<xref ref-type="other" rid="bib11">Greenblatt <italic>et al</italic>, 2001</xref>; <xref ref-type="other" rid="bib13">Manie <italic>et al</italic>, 2009</xref>). The observed interactions between <italic>TP53</italic> and <italic>BRCA</italic> pathways are integral to the progression of tumourigenesis in breast cancer.</p><p>A <italic>TP53</italic> polymorphism (rs1042522) has been found to be of functional significance, with the Pro72 allele being less efficient than Arg72 at inducing apoptosis, mainly due to weaker binding and ubiquitination by MDM2 of the Pro72 variant protein (<xref ref-type="other" rid="bib9">Dumont <italic>et al</italic>, 2003</xref>; <xref ref-type="other" rid="bib15">Osorio <italic>et al</italic>, 2006</xref>). An SNP in the promoter region of <italic>MDM2</italic> (309T>G, rs2279744) has been shown to increase <italic>MDM2</italic> transcriptional activity, thus attenuating the <italic>TP53</italic> pathway (<xref ref-type="other" rid="bib3">Bond <italic>et al</italic>, 2004</xref>). This latter SNP was associated with an earlier onset of breast cancer in Li–Fraumeni patients carrying <italic>TP53</italic> mutations (<xref ref-type="other" rid="bib4">Bougeard <italic>et al</italic>, 2006</xref>; <xref ref-type="other" rid="bib17">Ruijs <italic>et al</italic>, 2007</xref>). The effect on breast cancer risk of the <italic>TP53</italic> Arg72Pro and the <italic>MDM2</italic> 309T>G polymorphisms, separately and in combination, was investigated in a large case–control study by the Breast Cancer Association Consortium (BCAC), but no association was detected (<xref ref-type="other" rid="bib18">Schmidt <italic>et al</italic>, 2007</xref>). However, several smaller studies examined these polymorphisms in <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers (<xref ref-type="other" rid="bib14">Martin <italic>et al</italic>, 2003</xref>; <xref ref-type="other" rid="bib20">Tommiska <italic>et al</italic>, 2005</xref>; <xref ref-type="other" rid="bib7">Copson <italic>et al</italic>, 2006</xref>; <xref ref-type="other" rid="bib15">Osorio <italic>et al</italic>, 2006</xref>; <xref ref-type="other" rid="bib21">Wasielewski <italic>et al</italic>, 2007</xref>; <xref ref-type="other" rid="bib22">Yarden <italic>et al</italic>, 2008</xref>), and some suggested an association between the <italic>TP53</italic> Pro72 and the <italic>MDM2</italic> 309G alleles with an earlier age at breast cancer diagnosis (<xref ref-type="other" rid="bib14">Martin <italic>et al</italic>, 2003</xref>; <xref ref-type="other" rid="bib20">Tommiska <italic>et al</italic>, 2005</xref>; <xref ref-type="other" rid="bib15">Osorio <italic>et al</italic>, 2006</xref>; <xref ref-type="other" rid="bib22">Yarden <italic>et al</italic>, 2008</xref>). We therefore investigated the associations between breast cancer risk and these <italic>TP53</italic> and <italic>MDM2</italic> polymorphisms in a large series of <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers from the Consortium of Investigators of Modifiers of <italic>BRCA1</italic>/<italic>2</italic> (CIMBA) (<xref ref-type="other" rid="bib6">Chenevix-Trench <italic>et al</italic>, 2007</xref>).</p><sec sec-type="materials|methods"><title>Materials and methods</title><sec><title>Study sample</title><p>Eligibility was restricted to female carriers with pathogenic mutations in <italic>BRCA1</italic> or <italic>BRCA2</italic> who were ⩾18 years. Data were obtained from 13 CIMBA studies (<xref rid="tbl1" ref-type="table">Table 1</xref>). The majority of carriers were recruited through cancer genetics clinics offering genetic testing, and enrolled into national or regional studies. Information collected included the year of birth; mutation description; age at last followup; ages at breast and ovarian cancer diagnosis; and age at bilateral prophylactic mastectomy. Information was also available on the country of residence, which was defined to be the country of the clinic at which the carrier family was recruited for the study. Related individuals were identified through a unique family identifier. Further details of the information collected on the <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers and other details of the CIMBA initiative can be found elsewhere. Additional specific acknowledgements to the CIMBA collaborating centres are included in the <xref ref-type="other" rid="sup1">Supplementary Appendix</xref>. (<ext-link ext-link-type="uri" xlink:href="http://www.srl.cam.ac.uk/consortia/cimba/index.html">http://www.srl.cam.ac.uk/consortia/cimba/index.html</ext-link>) (<xref ref-type="other" rid="bib6">Chenevix-Trench <italic>et al</italic>, 2007</xref>). All carriers participated in clinical and research studies at the host institutions under IRB-approved protocols.</p></sec><sec><title>Genotyping</title><p>We pooled genotype data from studies within CIMBA that had previously genotyped polymorphisms rs1042522 and rs2279744 (see <xref rid="tbl1" ref-type="table">Table 1</xref>). Deviation from Hardy–Weinberg equilibrium among unrelated subjects was evaluated separately for each SNP and study. There was evidence for deviation for only one study (<italic>P</italic>=0.03), but cluster plot examination did not show any unusual pattern and the study was included in the analysis. Where available study specific genotyping quality control data were examined and data were included if the call rate was over 95% and the concordance among duplicates was over 98%.</p></sec><sec><title>Statistical analysis</title><p>Mutation carriers were classified according to their age at diagnosis of breast cancer or their age at last follow up. For this purpose, individuals were censored at the age of first breast cancer diagnosis, ovarian cancer diagnosis, bilateral prophylactic mastectomy or the age at last observation. Only individuals censored at breast cancer diagnosis were assumed to be affected (<xref rid="tbl2" ref-type="table">Table 2</xref>).</p><p>To correct for a potential bias related to the fact that <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers are not randomly sampled with respect to their disease status, the data were analysed within a survival analysis framework, by modelling the retrospective likelihood of the observed genotypes conditional on the disease phenotypes. A detailed description of the retrospective likelihood approach has been published (<xref ref-type="other" rid="bib1">Antoniou <italic>et al</italic>, 2007</xref>). We used a Cox proportional hazards model, where the effect of each SNP was modelled either as a per-allele hazard ratio (HR) or using separate HRs for heterozygotes and homozygotes. To assess the combined effects of the SNPs, we fitted a model in which a separate HR parameter was estimated for each multilocus genotype. More details of the statistical analysis can be found elsewhere (<xref ref-type="other" rid="bib2">Antoniou <italic>et al</italic>, 2008</xref>).</p></sec></sec><sec><title>Results</title><p>In total, 7011 <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers were genotyped for <italic>TP53</italic> Arg72Pro and 2222 mutation carriers were genotyped for <italic>MDM2</italic> 309T>G (<xref rid="tbl1" ref-type="table">Table 1</xref>). <xref rid="tbl2" ref-type="table">Table 2</xref> shows summary statistics for the cohort of <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers with an observed genotype for either the <italic>TP53</italic> or <italic>MDM2</italic> polymorphism. There was no evidence of an association between either SNP and breast cancer risk in <italic>BRCA1</italic> or <italic>BRCA2</italic> mutation carriers combined or analysed separately (<italic>TP53</italic> Arg72Pro: <italic>P</italic><sub>trend</sub>=0.89, 0.77 and 0.83, respectively; <italic>MDM2</italic> 309T>G: <italic>P</italic><sub>trend</sub>=0.60, 0.54 and 0.88, respectively) (<xref rid="tbl3" ref-type="table">Table 3</xref>). There was no evidence for heterogeneity in the HRs between studies (<italic>TP53</italic> Arg72Pro: <italic>P</italic>=0.22 and 0.93, <italic>MDM2</italic> 309T>G: <italic>P</italic>=0.11 and 0.82 for <italic>BRCA1</italic> or <italic>BRCA2</italic> mutation carriers respectively). The HRs for the 9 <italic>TP53–MDM2</italic> combined genotypes, estimated separately in <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers, ranged between 0.72 and 1.31, but none of them were significant.</p></sec><sec><title>Discussion</title><p>To our knowledge, this is the largest study to investigate the hypothesis that <italic>TP53</italic> Arg72Pro and <italic>MDM2</italic> 309T>G influence breast cancer risk in <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers individually or in combination. Our findings of no association for these SNPs suggest that they have little or no effect on <italic>BRCA</italic>-related breast cancer risk. These results are consistent with the absence of risk association in the recent <italic>TP53</italic> haplotype analysis, involving Arg72Pro and an intronic polymorphism c.97-147ins16 bp, in a series of 2932 <italic>BRCA1</italic> and <italic>BRCA2</italic> carriers from CIMBA (<xref ref-type="other" rid="bib16">Osorio <italic>et al</italic>, 2008</xref>). Our sample of mutation carriers had power of approximately 75% for <italic>TP53</italic> and 40% for <italic>MDM2</italic> to detect significant associations (<italic>P</italic><0.05) for a per-allele HR of 1.1 and power of 100 and 90% respectively for a HR of 1.2, suggesting that we can reliably dismiss previously suggested associations (<xref ref-type="other" rid="bib14">Martin <italic>et al</italic>, 2003</xref>; <xref ref-type="other" rid="bib15">Osorio <italic>et al</italic>, 2006</xref>; <xref ref-type="other" rid="bib22">Yarden <italic>et al</italic>, 2008</xref>).</p><p>Yarden <italic>et al</italic> showed that the <italic>MDM2</italic> GG genotype among Ashkenazi <italic>BRCA1/2</italic> mutations carriers was significantly associated with breast cancer diagnosed <italic>P</italic>=0.019) (<xref ref-type="other" rid="bib22">Yarden <italic>et al</italic>, 2008</xref>). However, we did not find any evidence of an increased risk for the GG homozygotes among the 217 carriers of the <italic>BRCA1</italic> Ashkenazi mutations 185delAG and 5382insC (HR=0.98, 95%CI 0.48–2.01) in this series.</p><p>The BCAC study of 5191 cases and 3834 controls found no evidence of an association of <italic>TP53</italic> Arg72Pro and <italic>MDM2</italic> 309T>G either with breast cancer overall or with oestrogen receptor (ER) status of tumours (<xref ref-type="other" rid="bib18">Schmidt <italic>et al</italic>, 2007</xref>). As the majority of <italic>BRCA1</italic> mutation-associated breast tumours are ER-negative (<xref ref-type="other" rid="bib12">Lakhani <italic>et al</italic>, 2005</xref>), the absence of an association in our study of breast cancer with the <italic>TP53</italic> and <italic>MDM2</italic> SNPs in <italic>BRCA1</italic> mutation carriers is consistent with the lack of an association with ER-negative cancers in the general population.</p></sec><pmc-comment>xmat handling</pmc-comment>
<sec sec-type="supplementary-material" id="sup1"><title>Supplementary Material</title><supplementary-material content-type="local-data" id="xob1"><caption><title>Supplementary Appendix</title></caption><media mimetype="application" mime-subtype="msword" xlink:href="6605279x1.doc"><label>Click here for supplemental data</label></media></supplementary-material></sec></body><back><ack><p>The CIMBA data management, DE, LM, SP, MC and EMBRACE are supported by Cancer Research UK Grants C1287/A10118 and C1287/A8874. CL is supported by Cancer Research UK Grant C8197/A10123. ACA is a Cancer Research – UK Senior Cancer Research Fellow.</p><p>Jacques Simard is Chairholder of the Canada Research Chair in Oncogenetics. This work was supported by the Canadian Institutes of Health Research for the ‘CIHR Team of Prediction and Communication of Familial Risks of Breast Cancer' program. Daniel Sinnett holds the François-Karl Viau Chair in Pediatric Oncogenomics and is a scholar of the Fonds de la Recherche en Santé du Québec (FRSQ).</p><p>We thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. The kConFab Clinical Follow Up Study has been funded by NHMRC grants 145684, 288704 and 454508. ABS and GCT are NHMRC fellows.</p><p>We gratefully acknowledge the contribution of Dr Jeffery P Struewing and Marbin Pineda for their laboratory support of this project. Drs Greene and Loud were supported by funding from the Intramural Research Program of the US National Cancer Institute, and from research contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Rockville, MD, USA.</p><p>The NICCC thanks the laboratory technicians Mrs. Irena Rimon and Mrs. Ana Gurtovnik for their technical support.</p><p>OCGN: We thank Mona Gill and Nayana Weerasooriya for assistance and we acknowledge funding from Cancer Care Ontario.</p><p>We thank Alicia Barroso, Concepción Hernandez and Anna Gonzalez for their technical support. The CNIO study was partially funded by the Asociación Española Contra el Cáncer (AECC), the Fundación Marató and the project PI081120 from the Ministry of Science and Innovation.</p><p>We thank Diana Torres and Muhammad U Rashid for providing DNA samples and supplying data. We thank Antje Seidel-Renkert for expert technical assistance. The DKFZ study was supported by the DKFZ.</p><p>The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI 2007-3756.</p><p>The investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. RE, EB and L D'M are also supported by Cancer Research UK Grant C5047/A8385. DGE and FL are supported the NIHR Biomedical Research Centre, Manchester.</p><p>We wish to thank all the GEMO collaborating members (Cancer Genetics Network ‘Groupe Génétique et Cancer', Fédération Nationale des Centres de Lutte Contre le Cancer, France) for their contribution to this study. The GEMO study was supported by the Ligue National Contre le Cancer and the Association ‘Le cancer du sein, parlons-en!' Award.</p><p>We thank Juliane Koehler for her excellent technical assistance and the 12 centers of the GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) for providing samples and clinical data. GC-HBOC is supported by a grant of the German Cancer Aid (grant 107054) and the Center for Molecular Medicine Cologne (grant TV93) to Rita K Schmutzler.</p><p>We thank Drs Kirsimari Aaltonen, Carl Blomqvist and RN Hanna Jäntti for their help with the patient data and Dr Johanna Tommiska for her kind help with the genetic analyses. The Finnish Cancer registry is gratefully acknowledged for the cancer data. The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (110663), Finnish Cancer Society and the Sigrid Juselius Foundation.</p></ack><notes><p><xref ref-type="other" rid="sup1">Supplementary Information</xref> accompanies the paper on British Journal of Cancer website (<ext-link ext-link-type="uri" xlink:href="http://www.nature.com/bjc">http://www.nature.com/bjc</ext-link>)</p></notes><ref-list><ref id="bib1"><citation citation-type="journal"><person-group 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<pub-id pub-id-type="pmid">18026875</pub-id></citation></ref></ref-list></back><floats-wrap><table-wrap id="tbl1" position="float"><label>Table 1</label><caption><p content-type="table-title">Number of <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers by study and by single nucleotide polymorphism (SNP)</p></caption><table frame="hsides" rules="groups" border="1" width="85%"><colgroup><col align="left"></col><col align="left"></col><col align="char" char="."></col><col align="char" char="."></col><col align="left"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><bold>Study</bold></th><th align="left" valign="top" charoff="50"><bold>Country</bold></th><th align="center" valign="top" char="." charoff="50"><bold><italic>TP53</italic> Arg72Pro (rs1042522)</bold></th><th align="center" valign="top" char="." charoff="50"><bold><italic>MDM2</italic> 309T>G (rs2279744)</bold></th><th align="left" valign="top" charoff="50"><bold>Genotyping platform</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">Spanish National Cancer Centre (CNIO)</td><td align="left" valign="top" charoff="50">Spain</td><td align="char" valign="top" char="." charoff="50">788</td><td align="char" valign="top" char="." charoff="50">0</td><td align="left" valign="top" charoff="50">Restriction enzyme digestion</td></tr><tr><td align="left" valign="top" charoff="50">Deutsches Krebsforschungszentrum (DKFZ)</td><td align="left" valign="top" charoff="50">Germany</td><td align="char" valign="top" char="." charoff="50">170</td><td align="char" valign="top" char="." charoff="50">0</td><td align="left" valign="top" charoff="50">PCR-based RFLP</td></tr><tr><td align="left" valign="top" charoff="50">Epidemiological study of <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers (EMBRACE)</td><td align="left" valign="top" charoff="50">U.K. and Eire</td><td align="char" valign="top" char="." charoff="50">1131</td><td align="char" valign="top" char="." charoff="50">0</td><td align="left" valign="top" charoff="50">iPLEX</td></tr><tr><td align="left" valign="top" charoff="50">Genetic Modifiers of cancer risk in <italic>BRCA1/2</italic> mutation carriers (GEMO)</td><td align="left" valign="top" charoff="50">France and U.S.A.</td><td align="char" valign="top" char="." charoff="50">1405</td><td align="char" valign="top" char="." charoff="50">1357</td><td align="left" valign="top" charoff="50">Taqman</td></tr><tr><td align="left" valign="top" charoff="50">German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC)</td><td align="left" valign="top" charoff="50">Germany</td><td align="char" valign="top" char="." charoff="50">815</td><td align="char" valign="top" char="." charoff="50">0</td><td align="left" valign="top" charoff="50">Taqman</td></tr><tr><td align="left" valign="top" charoff="50">Helsinki Breast Cancer Study (HEBCS)</td><td align="left" valign="top" charoff="50">Finland</td><td align="char" valign="top" char="." charoff="50">188</td><td align="char" valign="top" char="." charoff="50">187</td><td align="left" valign="top" charoff="50">rs1042522: Amplifluor(tm) fluorescent genotyping (Kbiosciences); rs2279744: RFLP</td></tr><tr><td align="left" valign="top" charoff="50">HEreditary Breast and Ovarian study Netherlands (HEBON)</td><td align="left" valign="top" charoff="50">The Netherlands</td><td align="char" valign="top" char="." charoff="50">438</td><td align="char" valign="top" char="." charoff="50">432</td><td align="left" valign="top" charoff="50">Taqman</td></tr><tr><td align="left" valign="top" charoff="50">INterdisciplinary HEalth Research International Team BReast CAncer susceptibility (INHERIT BRCAs)</td><td align="left" valign="top" charoff="50">Quebec-Canada</td><td align="char" valign="top" char="." charoff="50">146</td><td align="char" valign="top" char="." charoff="50">155</td><td align="left" valign="top" charoff="50">Taqman</td></tr><tr><td align="left" valign="top" charoff="50">kConFab</td><td align="left" valign="top" charoff="50">Australia</td><td align="char" valign="top" char="." charoff="50">790</td><td align="char" valign="top" char="." charoff="50">0</td><td align="left" valign="top" charoff="50">iPLEX</td></tr><tr><td align="left" valign="top" charoff="50">National Cancer Institute (NCI)</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="." charoff="50">190</td><td align="char" valign="top" char="." charoff="50">0</td><td align="left" valign="top" charoff="50">Taqman</td></tr><tr><td align="left" valign="top" charoff="50">National Israeli Cancer Control Center (NICCC)</td><td align="left" valign="top" charoff="50">Israel</td><td align="char" valign="top" char="." charoff="50">470</td><td align="char" valign="top" char="." charoff="50">0</td><td align="left" valign="top" charoff="50">Taqman</td></tr><tr><td align="left" valign="top" charoff="50">Ontario Cancer Genetics Network (OCGN)</td><td align="left" valign="top" charoff="50">Canada</td><td align="char" valign="top" char="." charoff="50">84</td><td align="char" valign="top" char="." charoff="50">91</td><td align="left" valign="top" charoff="50">Taqman</td></tr><tr><td align="left" valign="top" charoff="50">University of Pennsylvania (UPENN)</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="." charoff="50">396</td><td align="char" valign="top" char="." charoff="50">0</td><td align="left" valign="top" charoff="50">iPLEX</td></tr><tr><td align="left" valign="top" charoff="50">Total</td><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="." charoff="50">7011</td><td align="char" valign="top" char="." charoff="50">2222</td><td align="left" valign="top" charoff="50"> </td></tr></tbody></table></table-wrap><table-wrap id="tbl2" position="float"><label>Table 2</label><caption><p content-type="table-title">Summary characteristics for the 7109 eligible <italic>BRCA1</italic> and <italic>BRCA2</italic> carriers used in the analysis and typed for either single nucleotide polymorphism (SNP)</p></caption><table frame="hsides" rules="groups" border="1" width="85%"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th><th colspan="2" align="center" valign="top" charoff="50"><bold><italic>BRCA1</italic></bold></th><th colspan="2" align="center" valign="top" charoff="50"><bold><italic>BRCA2</italic></bold></th></tr><tr><th align="left" valign="top" charoff="50"><bold>Characteristic</bold></th><th align="center" valign="top" charoff="50"><bold>Unaffected</bold></th><th align="center" valign="top" charoff="50"><bold>Breast cancer</bold></th><th align="center" valign="top" charoff="50"><bold>Unaffected</bold></th><th align="center" valign="top" charoff="50"><bold>Breast cancer</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">Number</td><td align="center" valign="top" charoff="50">2055</td><td align="center" valign="top" charoff="50">2567</td><td align="center" valign="top" charoff="50">1051</td><td align="center" valign="top" charoff="50">1436</td></tr><tr><td align="left" valign="top" charoff="50">Person-years follow-up</td><td align="center" valign="top" charoff="50">87 571</td><td align="center" valign="top" charoff="50">104 679</td><td align="center" valign="top" charoff="50">46 315</td><td align="center" valign="top" charoff="50">63 080</td></tr><tr><td align="left" valign="top" charoff="50">Median age at censure (IQR)</td><td align="center" valign="top" charoff="50">41 (33–51)</td><td align="center" valign="top" charoff="50">40 (34–46)</td><td align="center" valign="top" charoff="50">42 (34–52)</td><td align="center" valign="top" charoff="50">43 (37–50)</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td colspan="5" align="left" valign="top" charoff="50"><italic>Age at censure (years), N</italic> (%)</td></tr><tr><td align="left" valign="top" charoff="50"> <30</td><td align="center" valign="top" charoff="50">327 (15.9)</td><td align="center" valign="top" charoff="50">225 (8.8)</td><td align="center" valign="top" charoff="50">139 (13.2)</td><td align="center" valign="top" charoff="50">78 (5.4)</td></tr><tr><td align="left" valign="top" charoff="50"> 30–39</td><td align="center" valign="top" charoff="50">584 (28.4)</td><td align="center" valign="top" charoff="50">1052 (41.0)</td><td align="center" valign="top" charoff="50">296 (28.1)</td><td align="center" valign="top" charoff="50">462 (32.2)</td></tr><tr><td align="left" valign="top" charoff="50"> 40–49</td><td align="center" valign="top" charoff="50">574 (27.9)</td><td align="center" valign="top" charoff="50">880 (34.3)</td><td align="center" valign="top" charoff="50">286 (27.2)</td><td align="center" valign="top" charoff="50">511 (35.6)</td></tr><tr><td align="left" valign="top" charoff="50"> 50–59</td><td align="center" valign="top" charoff="50">364 (17.7)</td><td align="center" valign="top" charoff="50">296 (11.5)</td><td align="center" valign="top" charoff="50">196 (18.7)</td><td align="center" valign="top" charoff="50">278 (19.4)</td></tr><tr><td align="left" valign="top" charoff="50"> 60–69</td><td align="center" valign="top" charoff="50">134 (6.5)</td><td align="center" valign="top" charoff="50">87 (3.4)</td><td align="center" valign="top" charoff="50">82 (7.8)</td><td align="center" valign="top" charoff="50">81 (5.6)</td></tr><tr><td align="left" valign="top" charoff="50"> 70+</td><td align="center" valign="top" charoff="50">72 (3.5)</td><td align="center" valign="top" charoff="50">27 (1.0)</td><td align="center" valign="top" charoff="50">52 (4.9)</td><td align="center" valign="top" charoff="50">26 (1.8)</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td colspan="5" align="left" valign="top" charoff="50"><italic>Year of birth, N</italic> (%)</td></tr><tr><td align="left" valign="top" charoff="50"> <1920</td><td align="center" valign="top" charoff="50">18 (0.9)</td><td align="center" valign="top" charoff="50">32 (1.3)</td><td align="center" valign="top" charoff="50">12 (1.1)</td><td align="center" valign="top" charoff="50">10 (0.7)</td></tr><tr><td align="left" valign="top" charoff="50"> 1920–29</td><td align="center" valign="top" charoff="50">63 (3.1)</td><td align="center" valign="top" charoff="50">117 (4.6)</td><td align="center" valign="top" charoff="50">39 (3.7)</td><td align="center" valign="top" charoff="50">83 (5.8)</td></tr><tr><td align="left" valign="top" charoff="50"> 1930–39</td><td align="center" valign="top" charoff="50">171 (8.3)</td><td align="center" valign="top" charoff="50">267 (10.4)</td><td align="center" valign="top" charoff="50">96 (9.1)</td><td align="center" valign="top" charoff="50">196 (13.7)</td></tr><tr><td align="left" valign="top" charoff="50"> 1940–49</td><td align="center" valign="top" charoff="50">326 (15.9)</td><td align="center" valign="top" charoff="50">657 (25.6)</td><td align="center" valign="top" charoff="50">143 (13.6)</td><td align="center" valign="top" charoff="50">358 (24.9)</td></tr><tr><td align="left" valign="top" charoff="50"> 1950–59</td><td align="center" valign="top" charoff="50">481 (23.4)</td><td align="center" valign="top" charoff="50">820 (31.9)</td><td align="center" valign="top" charoff="50">241 (22.9)</td><td align="center" valign="top" charoff="50">459 (32.0)</td></tr><tr><td align="left" valign="top" charoff="50"> 1960+</td><td align="center" valign="top" charoff="50">996 (48.5)</td><td align="center" valign="top" charoff="50">674 (26.3)</td><td align="center" valign="top" charoff="50">520 (49.5)</td><td align="center" valign="top" charoff="50">330 (23.0)</td></tr></tbody></table><table-wrap-foot><fn id="t2-fn1"><label></label><p>Abbreviation: IQR=interquartile range.</p></fn></table-wrap-foot></table-wrap><table-wrap id="tbl3" position="float"><label>Table 3</label><caption><p content-type="table-title">Genotype frequencies by mutant gene and breast cancer status with hazard ratio (HR) estimates</p></caption><table frame="hsides" rules="groups" border="1" width="85%"><colgroup><col align="left"></col><col align="char" char="("></col><col align="char" char="("></col><col align="char" char="."></col><col align="char" char="–"></col><col align="char" char="."></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th><th align="center" valign="top" char="(" charoff="50"><bold>Unaffected (%)</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>Affected (%)</bold></th><th align="center" valign="top" char="." charoff="50"><bold>HR</bold></th><th align="center" valign="top" char="–" charoff="50"><bold>95% CI</bold></th><th align="center" valign="top" char="." charoff="50"><bold><italic>P</italic>-value</bold></th></tr></thead><tbody valign="top"><tr><td colspan="6" align="left" valign="top" charoff="50"><italic>TP53 Arg72Pro (rs1042522)</italic></td></tr><tr><td colspan="6" align="left" valign="top" charoff="50"> <italic>BRCA1</italic>/2</td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="(" charoff="50">1660 (54.4)</td><td align="char" valign="top" char="(" charoff="50">2164 (54.7)</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GC</td><td align="char" valign="top" char="(" charoff="50">1178 (38.6)</td><td align="char" valign="top" char="(" charoff="50">1508 (38.1)</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="–" charoff="50">0.92–1.10</td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CC</td><td align="char" valign="top" char="(" charoff="50">214 (7.0)</td><td align="char" valign="top" char="(" charoff="50">287 (7.3)</td><td align="char" valign="top" char="." charoff="50">1.01</td><td align="char" valign="top" char="–" charoff="50">0.85–1.20</td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> 2-df test</td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50">0.99</td></tr><tr><td align="left" valign="top" charoff="50"> Per allele</td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50">1.01</td><td align="char" valign="top" char="–" charoff="50">0.94–1.08</td><td align="char" valign="top" char="." charoff="50">0.89</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="6" align="left" valign="top" charoff="50"> <italic>BRCA1</italic></td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="(" charoff="50">1127 (56.0)</td><td align="char" valign="top" char="(" charoff="50">1399 (55.2)</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GC</td><td align="char" valign="top" char="(" charoff="50">748 (37.2)</td><td align="char" valign="top" char="(" charoff="50">947 (37.4)</td><td align="char" valign="top" char="." charoff="50">1.01</td><td align="char" valign="top" char="–" charoff="50">0.90–1.13</td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CC</td><td align="char" valign="top" char="(" charoff="50">138 (6.9)</td><td align="char" valign="top" char="(" charoff="50">188 (7.4)</td><td align="char" valign="top" char="." charoff="50">1.03</td><td align="char" valign="top" char="–" charoff="50">0.84–1.27</td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> 2-df test</td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50">0.96</td></tr><tr><td align="left" valign="top" charoff="50"> Per allele</td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50">1.01</td><td align="char" valign="top" char="–" charoff="50">0.93–1.10</td><td align="char" valign="top" char="." charoff="50">0.77</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="6" align="left" valign="top" charoff="50"> <italic>BRCA2</italic></td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="(" charoff="50">533 (51.3)</td><td align="char" valign="top" char="(" charoff="50">765 (53.7)</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GC</td><td align="char" valign="top" char="(" charoff="50">430 (41.4)</td><td align="char" valign="top" char="(" charoff="50">561 (39.4)</td><td align="char" valign="top" char="." charoff="50">0.98</td><td align="char" valign="top" char="–" charoff="50">0.84–1.14</td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CC</td><td align="char" valign="top" char="(" charoff="50">76 (7.3)</td><td align="char" valign="top" char="(" charoff="50">99 (6.9)</td><td align="char" valign="top" char="." charoff="50">0.99</td><td align="char" valign="top" char="–" charoff="50">0.72–1.36</td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> 2-df test</td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50">0.95</td></tr><tr><td align="left" valign="top" charoff="50"> Per allele</td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50">0.99</td><td align="char" valign="top" char="–" charoff="50">0.87–1.12</td><td align="char" valign="top" char="." charoff="50">0.83</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="6" align="left" valign="top" charoff="50"><italic>MDM2 309T</italic>><italic>G (rs2279744)</italic></td></tr><tr><td colspan="6" align="left" valign="top" charoff="50"> <italic>BRCA1/2</italic></td></tr><tr><td align="left" valign="top" charoff="50"> TT</td><td align="char" valign="top" char="(" charoff="50">358 (40.3)</td><td align="char" valign="top" char="(" charoff="50">530 (39.8)</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> TG</td><td align="char" valign="top" char="(" charoff="50">405 (45.6)</td><td align="char" valign="top" char="(" charoff="50">615 (46.1)</td><td align="char" valign="top" char="." charoff="50">0.99</td><td align="char" valign="top" char="–" charoff="50">0.84–1.18</td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="(" charoff="50">126 (14.2)</td><td align="char" valign="top" char="(" charoff="50">188 (14.1)</td><td align="char" valign="top" char="." charoff="50">0.93</td><td align="char" valign="top" char="–" charoff="50">0.73–1.17</td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> 2-df test</td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50">0.79</td></tr><tr><td align="left" valign="top" charoff="50"> Per allele</td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50">0.97</td><td align="char" valign="top" char="–" charoff="50">0.87–1.08</td><td align="char" valign="top" char="." charoff="50">0.60</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="6" align="left" valign="top" charoff="50"> <italic>BRCA1</italic></td></tr><tr><td align="left" valign="top" charoff="50"> TT</td><td align="char" valign="top" char="(" charoff="50">275 (39.7)</td><td align="char" valign="top" char="(" charoff="50">369 (39.5)</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> TG</td><td align="char" valign="top" char="(" charoff="50">323 (46.6)</td><td align="char" valign="top" char="(" charoff="50">443 (47.4)</td><td align="char" valign="top" char="." charoff="50">0.98</td><td align="char" valign="top" char="–" charoff="50">0.81–1.19</td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="(" charoff="50">95 (13.7)</td><td align="char" valign="top" char="(" charoff="50">123 (13.2)</td><td align="char" valign="top" char="." charoff="50">0.91</td><td align="char" valign="top" char="–" charoff="50">0.67–1.19</td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> 2-df test</td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50">0.78</td></tr><tr><td align="left" valign="top" charoff="50"> Per allele</td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50">0.96</td><td align="char" valign="top" char="–" charoff="50">0.84–1.09</td><td align="char" valign="top" char="." charoff="50">0.54</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="6" align="left" valign="top" charoff="50"> <italic>BRCA2</italic></td></tr><tr><td align="left" valign="top" charoff="50"> TT</td><td align="char" valign="top" char="(" charoff="50">83 (42.4)</td><td align="char" valign="top" char="(" charoff="50">161 (40.5)</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> TG</td><td align="char" valign="top" char="(" charoff="50">82 (41.8)</td><td align="char" valign="top" char="(" charoff="50">172 (43.2)</td><td align="char" valign="top" char="." charoff="50">1.07</td><td align="char" valign="top" char="–" charoff="50">0.77–1.50</td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="(" charoff="50">31 (15.8)</td><td align="char" valign="top" char="(" charoff="50">65 (16.3)</td><td align="char" valign="top" char="." charoff="50">0.93</td><td align="char" valign="top" char="–" charoff="50">0.60–1.44</td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> 2-df test</td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="–" charoff="50"> </td><td align="char" valign="top" char="." charoff="50">0.83</td></tr><tr><td align="left" valign="top" charoff="50"> Per allele</td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="." charoff="50">0.98</td><td align="char" valign="top" char="–" charoff="50">0.80–1.21</td><td align="char" valign="top" char="." charoff="50">0.88</td></tr></tbody></table></table-wrap></floats-wrap></pmc>
