14346
2015
eng
e0120020
4
10
article
1
2017-01-27
--
--
Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers
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 p\(_{interaction}\) 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.
PLoS ONE
10.1371/journal.pone.0120020
urn:nbn:de:bvb:20-opus-143469
PLoS ONE 10(4): e0120020 (2015). DOI: 10.1371/journal.pone.0120020
CC 0: Public Domain Dedication
Ignacio Blanco
Karoline Kuchenbaecker
Daniel Cuadras
Xianshu Wang
Daniel Barrowdale
Gorka Ruiz de Garibay
Pablo Librado
Alejandro Sanchez-Gracia
Julio Rozas
Núria Bonifaci
Lesley McGuffog
Vernon S. Pankratz
Abul Islam
Francesca Mateo
Antoni Berenguer
Anna Petit
Isabel Català
Joan Brunet
Lidia Feliubadaló
Eva Tornero
Javier Benítez
Ana Osorio
Teresa Ramón y Cajal
Heli Nevanlinna
Kristina Aittomäki
Banu K. Arun
Amanda E. Toland
Beth Y. Karlan
Christine Walsh
Jenny Lester
Mark H. Greene
Phuong L. Mai
Robert L. Nussbaum
Irene L. Andrulis
Susan M. Domchek
Katherine L. Nathanson
Timothy R. Rebbeck
Rosa B. Barkardottir
Anna Jakubowska
Jan Lubinski
Katarzyna Durda
Katarzyna Jaworska-Bieniek
Kathleen Claes
Tom Van Maerken
Orland Díez
Thomas V. Hansen
Lars Jønson
Anne-Marie Gerdes
Bent Ejlertsen
Miguel De la Hoya
Trinidad Caldés
Alison M. Dunning
Clare Oliver
Elena Fineberg
Margaret Cook
Susan Peock
Emma McCann
Alex Murray
Chris Jacobs
Gabriella Pichert
Fiona Lalloo
Carol Chu
Huw Dorkins
Joan Paterson
Kai-Ren Ong
Manuel R. Teixeira
Frans B. L. Hogervorst
Annemarie H. Van der Hout
Caroline Seynaeve
Rob B. Van der Luijt
Marjolijn J. L. Ligtenberg
Peter Devilee
Juul T. Wijnen
Matti A. Rookus
Hanne E. J. Meijers-Heijboer
Marinus J. Blok
Ans M. W. Van den Ouweland
Cora M. Aalfs
Gustavo C. Rodriguez
Kelly-Anne A. Phillips
Marion Piedmonte
Stacy R. Nerenstone
Victoria L. Bae-Jump
David M. O'Malley
Rita K. Schmutzler
Barbara Wappenschmidt
Kerstin Rhiem
Christoph Engel
Alfons Meindl
Nina Ditsch
Norbert Arnold
Hansjoerg J. Plendl
Dieter Niederacher
Christian Sutter
Shan Wang-Gohrke
Doris Steinemann
Sabine Preisler-Adams
Karin Kast
Raymonda Varon-Mateeva
Andrea Gehrig
Anders Bojesen
Inge Sokilde Pedersen
Lone Sunde
Uffe Birk Jensen
Mads Thomassen
Torben A. Kruse
Lenka Foretova
Paolo Peterlongo
Loris Bernard
Bernard Peissel
Giulietta Scuvera
Siranoush Manoukian
Paolo Radice
Laura Ottini
Marco Montagna
Simona Agata
Christine Maugard
Jacques Simard
Penny Soucy
Andreas Berger
Anneliese Fink-Retter
Christian F. Singer
Christine Rappaport
Daphne Geschwantler-Kaulich
Muy-Kheng Tea
Georg Pfeiler
Esther M. John
Alex Miron
Susan L. Neuhausen
Mary Beth Terry
Wendy K. Chung
Mary B. Daly
David E. Goldgar
Ramunas Janavicius
Cecilia M. Dorfling
Elisabeth J. Van Rensburg
Florentia Fostira
Irene Konstantopoulou
Judy Garber
Andrew K. Godwin
Edith Olah
Steven A. Narod
Gad Rennert
Shani Shimon Paluch
Yael Laitman
Eitan Friedman
Annelie Liljegren
Johanna Rantala
Marie Stenmark-Askmalm
Niklas Loman
Evgeny N. Imyanitov
Ute Hamann
Amanda B. Spurdle
Sue Healey
Jeffrey N. Weitzel
Josef Herzog
David Margileth
Chiara Gorrini
Manel Esteller
Antonio Gómez
Sergi Sayols
Enrique Vidal
Holger Heyn
Dominique Stoppa-Lyonnet
Melanie Léoné
Laure Barjhoux
Marion Fassy-Colcombet
Antoine de Pauw
Christine Lasset
Sandra Fert Ferrer
Laurent Castera
Pascaline Berthet
François Cornelis
Yves-Jean Bignon
Francesca Damiola
Sylvie Mazoyer
Olga M. Sinilnikova
Christopher A. Maxwell
Joseph Vijai
Mark Robson
Noah Kauff
Marina J. Corines
Danylko Villano
Julie Cunningham
Adam Lee
Noralane Lindor
Conxi Lázaro
Douglas F. Easton
Kenneth Offit
Georgia Chenevix-Trench
Fergus J. Couch
Antonis C. Antoniou
Miguel Angel Pujana
eng
uncontrolled
genetic interaction networks
eng
uncontrolled
genome-wide association
eng
uncontrolled
expression signature
eng
uncontrolled
susceptibility loci
eng
uncontrolled
survival
eng
uncontrolled
modifiers
eng
uncontrolled
polymorphism
eng
uncontrolled
cell
eng
uncontrolled
chip-seq
eng
uncontrolled
elements
Menschliche Anatomie, Zytologie, Histologie
open_access
Institut für Humangenetik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14346/028_Blanco_PLOS ONE.pdf
11682
2014
eng
e1004256
4
article
SWE-BRCA ; HEBON ; kConFab Investigators
1
2015-07-27
--
--
DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7x10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95% CI: 1.03-1.21, p = 4.8x10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
PLOS Genetics
10.1371/journal.pgen.1004256
1553-7404
24698998
urn:nbn:de:bvb:20-opus-116820
PLoS Genetics 10(4): e1004256. doi:10.1371/journal.pgen.1004256
CC 0: Public Domain Dedication
Ana Osorio
Roger L. Milne
Karoline Kuchenbaecker
Tereza Vaclová
Guillermo Pita
Rosario Alonso
Paolo Peterlongo
Ignacio Blanco
Miguel de la Hoya
Mercedes Duran
Orland Diez
Teresa Ramón y Cajal
Irene Konstantopoulou
Christina Martínez-Bouzas
Raquel Andrés Conejero
Penny Soucy
Lesley McGuffog
Daniel Barrowdale
Andrew Lee
Brita Arver
Johanna Rantala
Niklas Loman
Hans Ehrencrona
Olufunmilayo I. Olopade
Mary S. Beattie
Susan M. Domchek
Katherine Nathanson
Timothy R. Rebbeck
Banu K. Arun
Beth Y. Karlan
Christine Walsh
Jenny Lester
Esther M. John
Alice S. Whittemore
Mary B. Daly
Melissa Southey
John Hopper
Mary B. Terry
Saundra S. Buys
Ramunas Janavicius
Cecilia M. Dorfling
Elizabeth J. van Rensburg
Linda Steele
Susan L. Neuhausen
Yuan Chun Ding
Thomas V. O. Hansen
Lars Jønson
Bent Ejlertsen
Anne-Marie Gerdes
Mar Infante
Belén Herráez
Leticia Thais Moreno
Jeffrey N. Weitzel
Josef Herzog
Kisa Weeman
Siranoush Manoukian
Bernard Peissel
Daniela Zaffaroni
Guilietta Scuvera
Bernardo Bonanni
Frederique Mariette
Sara Volorio
Alessandra Viel
Liliana Varesco
Laura Papi
Laura Ottini
Maria Grazia Tibiletti
Paolo Radice
Drakoulis Yannoukakos
Judy Garber
Steve Ellis
Debra Frost
Radka Platte
Elena Fineberg
Gareth Evans
Fiona Lalloo
Louise Izatt
Ros Eeles
Julian Adlard
Rosemarie Davidson
Trevor Cole
Diana Eccles
Jackie Cook
Shirley Hodgson
Carole Brewer
Marc Tischkowitz
Fiona Douglas
Mary Porteous
Lucy Side
Lisa Walker
Patrick Morrison
Alan Donaldson
John Kennedy
Claire Foo
Andrew K. Godwin
Rita Katharina Schmutzler
Barbara Wappenschmidt
Kerstin Rhiem
Christoph Engel
Alftons Meindl
Nina Ditsch
Norbert Arnold
Hans Jörg Plendl
Dieter Niederacher
Christian Sutter
Shan Wang-Gohrke
Doris Steinemann
Sabine Preisler-Adams
Karin Kast
Raymonda Varon-Mateeva
Andrea Gehrig
Dominique Stoppa-Lyonnet
Olga M. Sinilnikova
Sylvie Mazoyer
Francesca Damiola
Bruce Poppe
Kathleen Claes
Marion Piedmonte
Kathy Tucker
Floor Backes
Gustavo Rodríguez
Wendy Brewster
Katie Wakeley
Thomas Rutherford
Trinidad Caldés
Heli Nevanlinna
Kristiina Aittomäki
Matti A. Rookus
Theo A. M. van Os
Lizet van der Kolk
J. L. de Lange
Hanne E. J. Meijers-Heijboer
A. H. van der Hout
Christi J. van Asperen
Encarna B. Goméz Garcia
B. Encarna
Nicoline Hoogerbrugge
J. Margriet Collée
Carolien H. M. van Deurzen
Rob B. van der Luijt
Peter Devilee
Edith Olah
Conxi Lázaro
Alex Teulé
Mireia Menéndez
Anna Jakubowska
Cezary Cybulski
Jecek Gronwald
Jan Lubinski
Katarzyna Durda
Katarzyna Jaworska-Bieniek
Oskar Th. Johannsson
Christine Maugard
Marco Montagna
Silvia Tognazzo
Manuel R. Teixeira
Sue Healey
Curtis Olswold
Lucia Guidugli
Noralane Lindor
Susan Slager
Csilla I. Szabo
Joseph Vijai
Mark Robson
Noah Kauff
Liying Zhang
Rohini Rau-Murthy
Anneliese Fink-Retter
Christine F. Singer
Christine Rappaport
Daphne Geschwantler Kaulich
Georg Pfeiler
Muy-Kheng Tea
Andreas Berger
Catherine M. Phelan
Mark H. Greene
Phuong L. Mai
Flavio Lejbkowicz
Irene Andrulis
Anna Marie Mulligan
Gord Glendon
Amanda Ewart Toland
Anders Bojesen
Inge Sokilde Pedersen
Lone Sunde
Mads Thomassen
Torben A. Kruse
Uffe Birk Jensen
Eitan Friedman
Yeal Laitman
Shanie Paluch Shimon
Jaques Simard
Douglas F. Easton
Kenneth Offit
Fergus J. Couch
Georgia Chenevix-Trench
Antonis C. Antoniou
Javier Benitez
eng
uncontrolled
single-nucleotide polymorphisms
eng
uncontrolled
breast cancer
eng
uncontrolled
ovarian cancer
eng
uncontrolled
genetic modifiers
eng
uncontrolled
common variants
eng
uncontrolled
NEIL2
eng
uncontrolled
OGG1
eng
uncontrolled
investigators
eng
uncontrolled
consortium
eng
uncontrolled
damage
Medizin und Gesundheit
open_access
Institut für Humangenetik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11682/097_Osario_Plos_Genetics.pdf