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PLoS One. 2015 Apr 1;10(4):e0120020. doi: 10.1371/journal.pone.0120020. eCollection 2015.

Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers.

Blanco I1, Kuchenbaecker K2, Cuadras D3, Wang X4, Barrowdale D2, de Garibay GR5, Librado P6, Sánchez-Gracia A6, Rozas J6, Bonifaci N5, McGuffog L2, Pankratz VS7, Islam A8, Mateo F5, Berenguer A3, Petit A9, Català I9, Brunet J10, Feliubadaló L1, Tornero E1, Benítez J11, Osorio A11, Ramón y Cajal T12, Nevanlinna H13, Aittomäki K14, Arun BK15, Toland AE16, Karlan BY17, Walsh C17, Lester J17, Greene MH18, Mai PL18, Nussbaum RL19, Andrulis IL20, Domchek SM21, Nathanson KL21, Rebbeck TR22, Barkardottir RB23, Jakubowska A24, Lubinski J24, Durda K24, Jaworska-Bieniek K24, Claes K25, Van Maerken T25, Díez O26, Hansen TV27, Jønson L27, Gerdes AM28, Ejlertsen B29, de la Hoya M30, Caldés T30, Dunning AM2, Oliver C2, Fineberg E2, Cook M2, Peock S2, McCann E31, Murray A32, Jacobs C33, Pichert G33, Lalloo F34, Chu C35, Dorkins H36, Paterson J37, Ong KR38, Teixeira MR39; Teixeira, Hogervorst FB40, van der Hout AH41, Seynaeve C42, van der Luijt RB43, Ligtenberg MJ44, Devilee P45, Wijnen JT46, Rookus MA47, Meijers-Heijboer HE48, Blok MJ49, van den Ouweland AM50, Aalfs CM51, Rodriguez GC52, Phillips KA53, Piedmonte M54, Nerenstone SR55, Bae-Jump VL56, O'Malley DM57, Ratner ES58, Schmutzler RK59, Wappenschmidt B59, Rhiem K59, Engel C60, Meindl A61, Ditsch N62, Arnold N63, Plendl HJ64, Niederacher D65, Sutter C66, Wang-Gohrke S67, Steinemann D68, Preisler-Adams S69, Kast K70, Varon-Mateeva R71, Gehrig A72, Bojesen A73, Pedersen IS74, Sunde L75, Jensen UB75, Thomassen M76, Kruse TA76, Foretova L77, Peterlongo P78, Bernard L79, Peissel B80, Scuvera G80, Manoukian S80, Radice P81, Ottini L82, Montagna M83, Agata S83, Maugard C84, Simard J85, Soucy P85, Berger A86, Fink-Retter A86, Singer CF86, Rappaport C86, Geschwantler-Kaulich D86, Tea MK86, Pfeiler G86; BCFR, John EM87, Miron A88, Neuhausen SL89, Terry MB90, Chung WK91, Daly MB92, Goldgar DE93, Janavicius R94, Dorfling CM95, van Rensburg EJ95, Fostira F96, Konstantopoulou I96, Garber J97, Godwin AK98, Olah E99, Narod SA100, Rennert G101, Paluch SS102, Laitman Y103, Friedman E104; SWE-BRCA, Liljegren A105, Rantala J106, Stenmark-Askmalm M107, Loman N108, Imyanitov EN109, Hamann U110; kConFab Investigators, Spurdle AB111, Healey S111, Weitzel JN112, Herzog J112, Margileth D113, Gorrini C114, Esteller M115, Gómez A116, Sayols S116, Vidal E116, Heyn H116; GEMO, Stoppa-Lyonnet D117, Léoné M118, Barjhoux L119, Fassy-Colcombet M120, de Pauw A120, Lasset C121, Ferrer SF122, Castera L120, Berthet P123, Cornelis F124, Bignon YJ125, Damiola F119, Mazoyer S119, Sinilnikova OM126, Maxwell CA127, Vijai J128, Robson M128, Kauff N128, Corines MJ128, Villano D128, Cunningham J129, Lee A130, Lindor N131, Lázaro C1, Easton DF2, Offit K128, Chenevix-Trench G111, Couch FJ129, Antoniou AC2, Pujana MA5.

Collaborators (258)

Verny-Pierre C, Boutry-Kryza N, Calender A, Giraud S, Gauthier-Villars M, Buecher B, Houdayer C, Rouleau E, Golmard L, Collet A, Moncoutier V, Lefol C, Belotti M, Elan C, Nogues C, Fourme E, Birot AM, Bressac-de-Paillerets B, Caron O, Guillaud-Bataille M, Uhrhammer N, Bonadona V, Handallou S, Hardouin A, Vaur D, Sobol H, Bourdon V, Noguchi T, Remenieras A, Eisinger F, Coupier I, Pujol P, Peyrat JP, Fournier J, Révillion F, Vennin P, Adenis C, Muller D, Fricker JP, Barouk-Simonet E, Bonnet F, Bubien V, Sevenet N, Longy M, Toulas C, Guimbaud R, Gladieff L, Feillel V, Leroux D, Dreyfus H, Rebischung C, Peysselon M, Coron F, Faivre L, Prieur F, Lebrun M, Kientz C, Frénay M, Vénat-Bouvet L, Delnatte C, Mortemousque I, Coulet F, Colas C, Soubrier F, Warcoin M, Sokolowska J, Bronner M, Collonge-Rame MA, Damette A, Lynch HT, Snyder CL, Mazoyer S, Stoppa-Lyonnet D, Aghmesheh M, Amor D, Andrews L, Antill Y, Armitage S, Arnold L, Balleine R, Bankier A, Bastick P, Beesley J, Beilby J, Bennett B, Bennett I, Berry G, Blackburn A, Bogwitz M, Brennan M, Brown M, Buckley M, Burgess M, Burke J, Butow P, Byron K, Callen D, Campbell I, Chauhan D, Chauhan M, Chenevix-Trench G, Christian A, Clarke C, Colley A, Cotton D, Crook A, Cui J, Culling B, Cummings M, Dawson SJ, deFazio A, Delatycki M, Dickson R, Dixon J, Dobrovic A, Dudding T, Edkins T, Edwards S, Eisenbruch M, Farshid G, Fawcett S, Fellows A, Fenton G, Field M, Firgaira F, Flanagan J, Fleming J, Fong P, Forbes J, Fox S, French J, Friedlander M, Gaff C, Gardner M, Gattas M, George P, Giles G, Gill G, Goldblatt J, Greening S, Grist S, Haan E, Hardie K, Harris M, Hart S, Hayward N, Healey S, Heiniger L, Hopper J, Humphrey E, Hunt C, James P, Jenkins M, Jones A, Kefford R, Kidd A, Kiely B, Kirk J, Koehler J, Kollias J, Kovalenko S, Lakhani S, Leaming A, Leary J, Lim J, Lindeman G, Lipton L, Lobb L, Mann G, Marsh D, McLachlan SA, Meiser B, Meldrum C, Milne R, Mitchell G, Newman B, Niedermayr E, Nightingale S, O'Connell S, O'Loughlin I, Osborne R, Pachter N, Patterson B, Peters L, Phillips K, Price M, Purser L, Reeve T, Reeve J, Richards R, Rickard E, Robinson B, Rudzki B, Saleh M, Salisbury E, Sambrook J, Saunders C, Saunus J, Sayer R, Scott E, Scott R, Scott C, Seshadri R, Sexton A, Sharma R, Shelling A, Simpson P, Southey M, Spurdle A, Suthers G, Sykes P, Tassell M, Taylor D, Taylor J, Thierry B, Thomas S, Thompson E, Thorne H, Townshend S, Trainer A, Tran L, Tucker K, Tyler J, Visvader J, Walker L, Walpole I, Ward R, Waring P, Warner B, Warren G, Williams R, Wilson J, Winship I, Wu K, Young MA, Thorne H, Olsson H, Jernström H, Henriksson K, Harbst K, Soller M, Kristoffersson U, Öfverholm A, Nordling M, Karlsson P, Einbeigi Z, von Wachenfeldt A, Lindblom A, Arver B, Bustinza GB, Melin B, Ardnor CE, Emanuelsson M, Ehrencrona H, Pigg MH, Rosenquist R, Liedgren S, Borg Å.

Author information

1
Hereditary Cancer Program, Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Catalonia, Spain.
2
Epidemiological Study of Familial Breast Cancer (EMBRACE), Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
3
Statistics Unit, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Catalonia, Spain.
4
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, United States of America.
5
Breast Cancer and Systems Biology Unit, Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Catalonia, Spain.
6
Department of Genetics and Biodiversity Research Institute (IRBio), University of Barcelona, Barcelona, Catalonia, Spain.
7
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
8
Department of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka, Bangladesh.
9
Department of Pathology, University Hospital of Bellvitge, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Catalonia, Spain.
10
Hereditary Cancer Program, Catalan Institute of Oncology (ICO), Girona Biomedical Research Institute (IDIBGI), Hospital Josep Trueta, Girona, Catalonia, Spain.
11
Human Genetics Group, Spanish National Cancer Centre (CNIO), and Biomedical Network on Rare Diseases, Madrid, Spain.
12
Oncology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain.
13
Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
14
Department of Clinical Genetics, Helsinki University Central Hospital, Helsinki, Finland.
15
Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
16
Division of Human Cancer Genetics, Departments of Internal Medicine and Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America.
17
Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
18
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Maryland, Rockville, United States of America.
19
Department of Medicine and Genetics, University of California San Francisco, San Francisco, California, United States of America.
20
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
21
Abramson Cancer Center and Department of Medicine, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
22
Abramson Cancer Center and Center for Clinical Epidemiology and Biostatistics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
23
Department of Pathology, Landspitali University Hospital and BMC, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
24
Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
25
Center for Medical Genetics, Ghent University, Ghent, Belgium.
26
Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
27
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
28
Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
29
Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
30
Molecular Oncology Laboratory, Hospital Clínico San Carlos, San Carlos Research Institute (IdISSC), Madrid, Spain.
31
All Wales Medical Genetics Service, Glan Clwyd Hospital, Rhyl, United Kingdom.
32
All Wales Medical Genetics Services, Singleton Hospital, Swansea, United Kingdom.
33
Clinical Genetics, Guy's and St. Thomas' National Health Service (NHS) Foundation Trust, London, United Kingdom.
34
Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals National Health Service (NHS) Foundation Trust, Manchester, United Kingdom.
35
Yorkshire Regional Genetics Service, Leeds, United Kingdom.
36
North West Thames Regional Genetics Service, Kennedy-Galton Centre, Harrow, United Kingdom.
37
Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, United Kingdom.
38
West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare National Health Service (NHS) Trust, Edgbaston, Birmingham, United Kingdom.
39
Department of Genetics, Portuguese Oncology Institute, and Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal.
40
Family Cancer Clinic, Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
41
Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands.
42
Department of Medical Oncology, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands.
43
Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
44
Department of Human Genetics and Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands.
45
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
46
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
47
Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
48
Department of Clinical Genetics, Vrije Universiteit (VU) University Medical Centre, Amsterdam, The Netherlands.
49
Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
50
Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
51
Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
52
Division of Gynecologic Oncology, NorthShore University HealthSystem, University of Chicago, Chicago, Illinois, United States of America.
53
Division of Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
54
Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
55
Central Connecticut Cancer Consortium, Hartford Hospital/Helen and Harry Gray Cancer Center, Hartford, Connecticut, United States of America.
56
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
57
Division of Gynecologic Oncology, Ohio State University, Columbus Cancer Council, Hilliard, Ohio, United States of America.
58
Division of Gynecologic Oncology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
59
Centre of Familial Breast and Ovarian Cancer and Centre for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany.
60
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
61
Department of Gynecology and Obstetrics, Division of Tumor Genetics, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany.
62
Department of Gynecology and Obstetrics, Ludwig-Maximilian University Munich, Munich, Germany.
63
Department of Gynecology and Obstetrics, Christian-Albrechts-University of Kiel University Medical Center Schleswig-Holstein, Kiel, Germany.
64
Institute of Human Genetics, Christian-Albrechts-University of Kiel University Medical Center Schleswig-Holstein, Kiel, Germany.
65
Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
66
Institute of Human Genetics, Department of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany.
67
Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
68
Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany.
69
Institute of Human Genetics, University of Münster, Münster, Germany.
70
Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
71
Institute of Human Genetics, Campus Virchov Klinikum, Charite Berlin, Berlin, Germany.
72
Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics, University Würzburg, Würzburg, Germany.
73
Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark.
74
Section of Molecular Diagnostics, Department of Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
75
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
76
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
77
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
78
Fondazione Istituto di Oncologia Molecolare (IFOM), Fondazione Italiana per la Ricerca sul Cancro (FIRC), Milan, Italy.
79
Department of Experimental Oncology, Istituto Europeo di Oncologia (IEO), Cogentech Cancer Genetic Test Laboratory, Milan, Italy.
80
Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Istituto Nazionale Tumori (INT), Milan, Italy.
81
Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Istituto Nazionale Tumori (INT), Milan, Italy.
82
Department of Molecular Medicine, "Sapienza" University, Rome, Italy.
83
Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto (IOV), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua, Italy.
84
Laboratoire de Diagnostic Génétique et Service d'Onco-Hématologie, Hopitaux Universitaire de Strasbourg, Centre Hospitalier Régional Universitaire (CHRU) Nouvel Hôpital Civil, Strasbourg, France.
85
Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center and Laval University, Quebec City, Canada.
86
Department of Gynecology and Obstetrics, and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
87
Department of Epidemiology, Cancer Prevention Institute of California, Fremont, California, United States of America.
88
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
89
Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California, United States of America.
90
Department of Epidemiology, Columbia University, New York, New York, United States of America.
91
Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, New York, United States of America.
92
Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
93
Department of Dermatology, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
94
Vilnius University Hospital Santariskiu Clinics, Hematology, Oncology and Transfusion Medicine Center, Department of Molecular and Regenerative Medicine, State Research Centre Institute for Innovative medicine, Vilnius, Lithuania.
95
Cancer Genetics Laboratory, Department of Genetics, University of Pretoria, Arcadia, South Africa.
96
Molecular Diagnostics Laboratory, Institute of Radioisotopes and Radiodiagnostic Products (IRRP), National Centre for Scientific Research Demokritos, Athens, Greece.
97
Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States of America.
98
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
99
Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.
100
Women's College Research Institute, University of Toronto, Toronto, Canada.
101
Clalit National Israeli Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and B Rappaport Faculty of Medicine, Haifa, Israel.
102
The Institute of Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel.
103
The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Chaim Sheba Medical Center, Ramat Gan, Israel.
104
The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Chaim Sheba Medical Center, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
105
Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
106
Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
107
Division of Clinical Genetics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
108
Department of Oncology, Lund University Hospital, Lund, Sweden.
109
N.N. Petrov Institute of Oncology, St.-Petersburg, Russia.
110
Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
111
Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Brisbane, Australia.
112
Clinical Cancer Genetics, City of Hope, Duarte, California, United States of America.
113
St. Joseph Hospital of Orange, Care of City of Hope Clinical Cancer Genetics Community Research Network, Duarte, California, United States of America.
114
The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, Canada.
115
Cancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Catalonia, Spain; Department of Physiological Sciences II, School of Medicine, University of Barcelona, L'Hospitalet del Llobregat, Catalonia, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Catalonia, Spain.
116
Cancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Catalonia, Spain.
117
Department of Tumour Biology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U830, Institut Curie, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
118
Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon-Centre Léon Bérard, Lyon, France.
119
Institut National de la Santé et de la Recherche Médicale (INSERM) U1052, Centre National de la Recherche Scientifique (CNRS) UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
120
Department of Tumour Biology, Institut Curie, Paris, France.
121
Université Lyon 1, Centre National de la Recherche Scientifique (CNRS) UMR5558, and Unité de Prévention et d'Epidémiologie Génétique, Centre Léon Bérard, Lyon, France.
122
Laboratoire de Génétique Chromosomique, Hôtel Dieu Centre Hospitalier, Chambéry, France.
123
Centre François Baclesse, Caen, France.
124
Genetic Unit, Avicenne Hospital, Assitance Publique-Hôpitaux de Paris, Paris, Sud-Francilien Hospital, Evry-Corbeil, and University Hospital, Clermont-Ferrand, France.
125
Département d'Oncogénétique, Centre Jean Perrin, Université de Clermont-Ferrand, Clermont-Ferrand, France.
126
Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon-Centre Léon Bérard, Lyon, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U1052, Centre National de la Recherche Scientifique (CNRS) UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
127
Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, Canada.
128
Clinical Genetics Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
129
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, United States of America; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
130
Department of Oncology, Mayo Clinic, Rochester, Minnesota, United States of America.
131
Center for Individualized Medicine, Mayo Clinic, Scottsdale, Arizona, United States of America.

Abstract

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

PMID:
25830658
PMCID:
PMC4382299
DOI:
10.1371/journal.pone.0120020
[Indexed for MEDLINE]
Free PMC Article

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