13044
2012
eng
R33
14
article
CIMBA; SWE-BRCA; HEBON; EMBRACE; GEMO Study Collaborators; kConFab Investigators
1
2016-03-22
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--
Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers
Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2).
Methods: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework.
Results: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 x 10\(^{-4}\)). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 x 10\(^{-5}\), P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df P = 0.007; rs1292011 2df P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 x 10\(^{-5}\)) and there was marginal evidence of association with ER- negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049).
Conclusions: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.
Breast Cancer Research
10.1186/bcr3121
urn:nbn:de:bvb:20-opus-130449
Breast Cancer Research 2012, 14:R33. DOI:10.1186/bcr3121
223175
Antonis C. Antoniou
Karoline B. Kuchenbaecker
Penny Soucy
Jonathan Beesley
Xiaoqing Chen
Lesley McGuffog
Andrew Lee
Daniel Barrowdale
Sue Healey
Olga M. Sinilnikova
Maria A. Caligo
Niklas Loman
Katja Harbst
Annika Lindblom
Brita Arver
Richard Rosenquist
Per Karlsson
Kate Nathanson
Susan Domchek
Tim Rebbeck
Anna Jakubowska
Jan Lubinski
Katarzyna Jaworska
Katarzyna Durda
Elżbieta Zlowowcka-Perłowska
Ana Osorio
Mercedes Durán
Raquel Andrés
Javier Benítez
Ute Hamann
Frans B. Hogervorst
Theo A. van Os
Senno Verhoef
Hanne E. J. Meijers-Heijboer
Juul Wijnen
Encarna B. Gómez Garcia
Marjolijn J. Ligtenberg
Mieke Kriege
Margriet Collée
Margreet G. E. M. Ausems
Jan C. Oosterwijk
Susan Peock
Debra Frost
Steve D. Ellis
Radka Platte
Elena Fineberg
D. Gareth Evans
Fiona Lalloo
Chris Jacobs
Ros Eeles
Julian Adlard
Rosemarie Davidson
Trevor Cole
Jackie Cook
Joan Paterson
Fiona Douglas
Carole Brewer
Shirley Hodgson
Patrick J. Morrison
Lisa Walker
Mark T. Rogers
Alan Donaldson
Huw Dorkins
Andrew K. Godwin
Betsy Bove
Dominique Stoppa-Lyonnet
Claude Houdayer
Bruno Buecher
Antoine de Pauw
Sylvie Mazoyer
Alain Calender
Mélanie Léoné
Brigitte Bressac-de Paillerets
Olivier Caron
Hagay Sobol
Marc Frenay
Fabienne Prieur
Sandra Fert Ferrer
Isabelle Mortemousque
Saundra Buys
Mary Daly
Alexander Miron
Mary Beth Terry
John L. Hopper
Esther M. John
Melissa Southey
David Goldgar
Christian F. Singer
Anneliese Fink-Retter
Tea Muy-Kheng
Daphne Geschwantler Kaulich
Thomas V. O. Hansen
Finn C. Nielsen
Rosa B. Barkardottir
Mia Gaudet
Tomas Kirchhoff
Vijai Joseph
Ana Dutra-Clarke
Kenneth Offit
Marion Piedmonte
Judy Kirk
David Cohn
Jean Hurteau
John Byron
James Fiorica
Amanda E. Toland
Marco Montagna
Cristina Oliani
Evgeny Imyanitov
Claudine Isaacs
Laima Tihomirova
Ignacio Blanco
Conxi Lazaro
Alex Teulé
J. Del Valle
Simon A. Gayther
Kunle Odunsi
Jenny Gross
Beth Y. Karlan
Edith Olah
Soo-Hwang Teo
Patricia A. Ganz
Mary S. Beattie
Cecelia M. Dorfling
Elizabeth Jansen van Rensburg
Orland Diez
Ava Kwong
Rita K. Schmutzler
Barbara Wappenschmidt
Christoph Engel
Alfons Meindl
Nina Ditsch
Norbert Arnold
Simone Heidemann
Dieter Niederacher
Sabine Preisler-Adams
Dorothea Gadzicki
Raymonda Varon-Mateeva
Helmut Deissler
Andrea Gehrig
Christian Sutter
Karin Kast
Britta Fiebig
Dieter Schäfer
Trinidad Caldes
Miguel de la Hoya
Heli Nevanlinna
Taru A. Muranen
Bernard Lespérance
Amanda B. Spurdle
Susan L. Neuhausen
Yuan C. Ding
Xianshu Wang
Zachary Fredericksen
Vernon S. Pankratz
Noralane M. Lindor
Paulo Peterlongo
Siranoush Manoukian
Bernard Peissel
Daniela Zaffaroni
Bernardo Bonanni
Loris Bernard
Riccardo Dolcetti
Laura Papi
Laura Ottini
Paolo Radice
Mark H. Greene
Jennifer T. Loud
Irene L. Andrulis
Hilmi Ozcelik
Anna Marie Mulligan
Gord Glendon
Mads Thomassen
Anne-Marie Gerdes
Uffe B. Jensen
Anne-Bine Skytte
Torben A. Kruse
Georgia Chenevix-Trench
Fergus J. Couch
Jacques Simard
Douglas F. Easton
eng
uncontrolled
investigators
eng
uncontrolled
genetic modifiers
eng
uncontrolled
mammographic density
eng
uncontrolled
susceptibility loci
eng
uncontrolled
ovarian cancer
eng
uncontrolled
hormone-related protein
eng
uncontrolled
genome-wide association
eng
uncontrolled
tumor subtypes
eng
uncontrolled
alleles
eng
uncontrolled
consortium
Menschliche Anatomie, Zytologie, Histologie
open_access
Institut für Humangenetik
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13044/Antoniou_A10.1186-Fbcr3121.pdf
14346
2015
eng
e0120020
4
10
article
1
2017-01-27
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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