12794
2013
eng
e1003212
3
9
article
1
2016-02-25
--
--
Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk
BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
PLOS Genetics
10.1371/journal.pgen.1003212
1553-7404
urn:nbn:de:bvb:20-opus-127947
PLoS Genetics 9(3): e1003212. doi:10.1371/journal.pgen.1003212
223175
Fergus J. Couch
Xianshu Wang
Lesley McGuffog
Andrew Lee
Curtis Olswold
Karoline B. Kuchenbaecker
Penny Soucy
Zachary Fredericksen
Daniel Barrowdale
Joe Dennis
Mia M. Gaudet
Ed Dicks
Matthew Kosel
Sue Healey
Olga M. Sinilnikova
Adam Lee
Françios Bacot
Daniel Vincent
Frans B. L. Hogervorst
Susan Peock
Dominique Stoppa-Lyonnet
Anna Jakubowska
Paolo Radice
Rita Katharina Schmutzler
Susan M. Domchek
Marion Piedmonte
Christian F. Singer
Eitan Friedman
Mads Thomassen
Thomas V. O. Hansen
Susan L. Neuhausen
Csilla I. Szabo
Ingnacio Blanco
Mark H. Greene
Beth Y. Karlan
Judy Garber
Catherine M. Phelan
Jeffrey N. Weitzel
Marco Montagna
Edith Olah
Irene L. Andrulis
Andrew K. Godwin
Drakoulis Yannoukakos
David E. Goldgar
Trinidad Caldes
Heli Nevanlinna
Ana Osorio
Mary Beth Terry
Mary B. Daly
Elisabeth J. van Rensburg
Ute Hamann
Susan J. Ramus
Amanda Ewart Toland
Maria A. Caligo
Olufunmilayo I. Olopade
Nadine Tung
Kathleen Claes
Mary S. Beattie
Melissa C. Southey
Evgeny N. Imyanitov
Marc Tischkowitz
Ramunas Janavicius
Esther M. John
Ava Kwong
Orland Diez
Ava Kwong
Judith Balmaña
Rosa B. Barkardottir
Banu K. Arun
Gad Rennert
Soo-Hwang Teo
Patricia A. Ganz
Ian Campbell
Annemarie H. van der Hout
Carolien H. M. van Deurzen
Caroline Seynaeve
Encarna B. Gómez Garcia
Flora E. van Leeuwen
Hanne E. J. Meijers-Heijboer
Johannes J. P. Gille
Magreet G. E. M. Ausems
Marinus J. Blok
Marjolinjin J. L. Ligtenberg
Matti A. Rookus
Peter Devilee
Senno Verhoef
Theo A. M. van Os
Juul T. Wijnen
Debra Frost
Steve Ellis
Elena Fineberg
Radke Platte
D. Gareth Evans
Luise Izatt
Rosalind A. Eeles
Julian Adlard
Diana M. Eccles
Jackie Cook
Carole Brewer
Fiona Douglas
Shirley Hodgson
Patrick J. Morrison
Lucy E. Side
Alan Donaldson
Catherine Houghton
Mark T. Rogers
Huw Dorkins
Jacqueline Eason
Helen Gregory
Emma McCann
Alex Murray
Alain Calender
Agnès Hardouin
Pascaline Berthet
Capucine Delnatte
Catherine Nogues
Christine Lasset
Claude Houdayer
Dominique Leroux,
Etienne Rouleau
Fabienne Prieur
Francesca Damiola
Hagay Sobol
Isabelle Coupier
Laurence Venat-Bouvet
Laurent Castera
Marion Gauthier-Villars
Mélanie Léoné
Pascal Pujol
Sylvie Mazoyer
Yves-Jean Bignon
Elzbieta Zlowocka-Perlowska
Jacek Gronwald
Jan Lubinski,
Katarzyna Durda
Katarzyna Jaworska
Tomasz Huzarski
Amanda B. Spurdle
Alessandra Viel
Bernhard Peissel
Bernardo Bonanni
Guilia Melloni
Laura Ottini
Laura Papi
Liliana Varesco
Maria Grazia Tibiletti
Paolo Peterlongo
Sara Volorio
Siranoush Manoukian
Valeria Pensotti
Norbert Arnold
Christoph Engel
Helmut Deissler
Dorothea Gadzicki
Andrea Gehrig
Karin Kast
Kerstin Rhiem
Alfons Meindl
Dieter Niederacher
Nina Ditsch
Hansjoerg Plendl
Sabine Preisler-Adams
Stefanie Engert
Christian Sutter
Raymenda Varon-Mateeva
Barbara Wappenschmidt
Bernhard H. F. Weber
Brita Arver
Marie Stenmark-Askmalm
Niklas Loman
Richard Rosenquist
Zakaria Einbeigi
Katherine L. Nathanson
Timothy R. Rebbeck
Stephanie V. Blank
David E. Cohn
Gustavo C. Rodriguez
Laurie Small
Michael Friedlander
Victoria L. Bae-Jump
Anneliese Fink-Retter
Christine Rappaport
Daphne Gschwantler-Kaulich
Georg Pfeiler
Muy-Kheng Tea
Noralane M. Lindor
Bella Kaufman
Shani Shimon Paluch
Yael Laitman
Anne-Bine Skytte
Anne-Marie Gerdes
Inge Sokilde Pedersen
Sanne Traasdahl Moeller
Torben A. Kruse
Uffe Birk Jensen
Joseph Vijai
Kara Sarrel
Mark Robson
Noah Kauff
Anna Marie Mulligan
Gord Glendon
Hilmi Ozcelik
Bent Ejlertsen
Finn C. Nielsen
Lars Jønson
Mette K. Andersen
Yuan Chun Ding
Linda Steele
Lenka Foretova
Alex Teulé
Conxi Lazaro
Joan Brunet
Miquel Angel Pujana
Phuong L. Mai
Jennifer T. Loud
Christine Walsh
Jenny Lester
Sandra Orsulic
Steven A. Narod
Josef Herzog
Sharon R. Sand
Silvia Tognazzo
Simona Agata
Tibor Vaszko
Joellen Weaver
Alexandra V. Stravropoulou
Saundra S. Buys
Atocha Romero
Miguel de la Hoya
Kristiina Aittomäki
Taru A. Muranen
Mercedes Duran
Wendy K. Chung
Adriana Lasa
Cecilia M. Dorfling
Alexander Miron
Javier Benitez
Leigha Senter
Dezheng Huo
Salina B. Chan
Anna P. Sokolenko
Jocelyne Chiquette
Laima Tihomirova
Tara M. Friebel
Bjarne A. Agnarsson
Karen H. Lu
Flavio Lejbkowicz
Paul A. James
Per Hall
Alison M. Dunning
Daniel Tessier
Julie Cunningham
Susan L. Slager
Wang Chen
Steven Hart
Kristen Stevens
Jacques Simard
Tomi Pastinen
Vernon S. Pankratz
Kenneth Offit
Douglas F. Easton
Georgia Chenevix-Trench
Antonis C. Antoniou
eng
uncontrolled
common variants
eng
uncontrolled
susceptibility alleles
eng
uncontrolled
genetic variants
eng
uncontrolled
modifiers
eng
uncontrolled
ZNF365
eng
uncontrolled
investigators
eng
uncontrolled
population
eng
uncontrolled
consortium
eng
uncontrolled
selection
eng
uncontrolled
subtypes
Inzidenz und Prävention von Krankheiten
open_access
Institut für Humangenetik
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12794/063_Couch_Plos_Genetics.pdf
12737
2013
eng
e1003864
10
9
article
1
2016-02-18
--
--
Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
PLoS Genetics
10.1371/journal.pgen.1003864
1553-7390
urn:nbn:de:bvb:20-opus-127377
PLoS Genetics 9(10): e1003864. doi:10.1371/journal.pgen.1003864
Lea K. Davis
Dongmei Yu
Clare L. Keenan
Eric R. Gamazon
Anuar I. Konkashbaev
Eske M. Derks
Benjamin M. Neale
Jian Yang
S. Hong Lee
Patrick Evans
Cathy L. Barr
Laura Bellodi
Fortu Benarroch
Gabriel Bedoya Berrio
Oscar J. Bienvenu
Michael H. Bloch
Rianne M. Blom
Ruth D. Bruun
Cathy L. Budman
Beatriz Camarena
Desmond Campbell
Carolina Cappi
Julio C. Cardona Silgado
Danielle C. Cath
Maria C. Cavallini
Denise A. Chavira
Sylvian Chouinard
David V. Conti
Edwin H. Cook
Vladimir Coric
Bernadette A. Cullen
Dieter Deforce
Richard Delorme
Yves Dion
Christopher K. Edlund
Karin Egberts
Peter Falkai
Thomas V. Fernandez
Patience J. Gallagher
Helena Garrido
Daniel Geller
Simon L. Girard
Hans J. Grabe
Marco A. Grados
Benjamin D. Greenberg
Varda Gross-Tsur
Stephen Haddad
Gary A. Heiman
Sian M. J. Hemmings
Ana G. Hounie
Cornelia Illmann
Joseph Jankovic
Micheal A. Jenike
James L. Kennedy
Robert A. King
Barbara Kremeyer
Roger Kurlan
Nuria Lanzagorta
Marion Leboyer
James F. Leckman
Leonhard Lennertz
Chunyu Liu
Christine Lochner
Thomas L. Lowe
Fabio Macciardi
James T. McCracken
Lauren M. McGrath
Sandra C. Mesa Restrepo
Rainald Moessner
Jubel Morgan
Heike Muller
Dennis L. Murphy
Allan L. Naarden
William Cornejo Ochoa
Roel A. Ophoff
Lisa Osiecki
Andrew J. Pakstis
Michele T. Pato
Carlos N. Pato
John Piacentini
Christopher Pittenger
Yehunda Pollak
Scott L. Rauch
Tobias J. Renner
Victor I. Reus
Margaret A. Richter
Mark A. Riddle
Mary M. Robertson
Roxana Romero
Maria C. Rosàrio
David Rosenberg
Guy A. Rouleau
Stephan Ruhrmann
Andreas Ruiz-Linares
Aline S. Sampaio
Jack Samuels
Paul Sandor
Broke Sheppard
Harvey S. Singer
Jan H. Smit
Dan J. Stein
E. Strengman
Jay A. Tischfield
Ana V. Valencia Duarte
Homero Vallada
Flip Van Nieuwerburgh
Jeremy Veenstra-VanderWeele
Susanne Walitza
Ying Wang
Jens R. Wendland
Herman G. M. Westenberg
Yin Yao Shugart
Euripedes C. Miguel
William McMahon
Michael Wagner
Humberto Nicolini
Danielle Posthuma
Gregory L. Hanna
Peter Heutink
Damiaan Denys
Paul D. Arnold
Ben A. Oostra
Gerald Nestadt
Nelson B. Freimer
David L. Pauls
Naomi R. Wray
S. Evelyn Stewart
Carol A. Mathews
James A. Knowles
Nancy J. Cox
Jeremiah M. Scharf
eng
uncontrolled
TIC disorders
eng
uncontrolled
missing heritability
eng
uncontrolled
complex diseases
eng
uncontrolled
neuropsychiatric disorders
eng
uncontrolled
common SNPS
eng
uncontrolled
gilles
eng
uncontrolled
family
eng
uncontrolled
brain
eng
uncontrolled
expression
eng
uncontrolled
autism
Krankheiten
open_access
Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12737/058_Davis_Plos_Genetics.pdf
13044
2012
eng
R33
14
article
CIMBA; SWE-BRCA; HEBON; EMBRACE; GEMO Study Collaborators; kConFab Investigators
1
2016-03-22
--
--
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
16622
2016
eng
10165
7
article
1
2018-08-01
--
--
Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.
Nature Communications
10.1038/ncomms10165
urn:nbn:de:bvb:20-opus-166221
Nature Communications, 2016, 7:10165. DOI: 10.1038/ncomms10165
260986
616346
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Joshua B. Benoit
Zach N. Adelman
Klaus Reinhardt
Amanda Dolan
Monica Poelchau
Emily C. Jennings
Elise M. Szuter
Richard W. Hagan
Hemant Gujar
Jayendra Nath Shukla
Fang Zhu
M. Mohan
David R. Nelson
Andrew J. Rosendale
Christian Derst
Valentina Resnik
Sebastian Wernig
Pamela Menegazzi
Christian Wegener
Nicolai Peschel
Jacob M. Hendershot
Wolfgang Blenau
Reinhard Predel
Paul R. Johnston
Panagiotis Ioannidis
Robert M. Waterhouse
Ralf Nauen
Corinna Schorn
Mark-Christoph Ott
Frank Maiwald
J. Spencer Johnston
Ameya D. Gondhalekar
Michael E. Scharf
Kapil R. Raje
Benjamin A. Hottel
David Armisén
Antonin Jean Johan Crumière
Peter Nagui Refki
Maria Emilia Santos
Essia Sghaier
Sèverine Viala
Abderrahman Khila
Seung-Joon Ahn
Christopher Childers
Chien-Yueh Lee
Han Lin
Daniel S.T. Hughes
Elizabeth J. Duncan
Shwetha C. Murali
Jiaxin Qu
Shannon Dugan
Sandra L. Lee
Hsu Chao
Huyen Dinh
Yi Han
Harshavardhan Doddapaneni
Kim C. Worley
Donna M. Muzny
David Wheeler
Kristen A. Panfilio
Iris M. Vargas Jentzsch
IMV Jentzsch
Edward L. Vargo
Warren Booth
Markus Friedrich
Matthew T. Weirauch
Michelle A.E. Anderson
Jeffery W. Jones
Omprakash Mittapalli
Chaoyang Zhao
Jing-Jiang Zhou
Jay D. Evans
Geoffrey M. Attardo
Hugh M. Robertson
Evgeny M. Zdobnov
Jose M.C. Ribeiro
Richard A. Gibbs
John H. Werren
Subba R. Palli
Coby Schal
Stephen Richards
eng
uncontrolled
human ectoparasite
eng
uncontrolled
bed bug
eng
uncontrolled
Cimex lectularius
eng
uncontrolled
genome
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16622/Benoit_Nature_Communications.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
14545
2015
eng
61
17
article
1
2017-03-07
--
--
An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers
Introduction:
Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers.
Methods:
We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals.
Results:
We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk.
Conclusions:
This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.
Breast Cancer Research
10.1186/s13058-015-0567-2
urn:nbn:de:bvb:20-opus-145458
Breast Cancer Research (2015) 17:61. DOI: 10.1186/s13058-015-0567-2
223175
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Sophie Blein
Claire Bardel
Vincent Danjean
Lesley McGuffog
Sue Healay
Daniel Barrowdale
Andrew Lee
Joe Dennis
Karoline B. Kuchenbaecker
Penny Soucy
Mary Beth Terry
Wendy K. Chung
David E. Goldgar
Saundra S. Buys
Ramunas Janavicius
Laima Tihomirova
Nadine Tung
Cecilia M. Dorfling
Elizabeth J. van Rensburg
Susan L. Neuhausen
Yuan Chun Ding
Anne-Marie Gerdes
Bent Ejlertsen
Finn C. Nielsen
Thomas V. O. Hansen
Ana Osorio
Javier Benitez
Raquel Andreas Conejero
Ena Segota
Jeffrey N. Weitzel
Margo Thelander
Paolo Peterlongo
Paolo Radice
Valeria Pensotti
Riccardo Dolcetti
Bernardo Bonanni
Bernard Peissel
Daniela Zaffaroni
Giulietta Scuvera
Siranoush Manoukian
Liliana Varesco
Gabriele L. Capone
Laura Papi
Laura Ottini
Drakoulis Yannoukakos
Irene Konstantopoulou
Judy Garber
Ute Hamann
Alan Donaldson
Angela Brady
Carole Brewer
Claire Foo
D. Gareth Evans
Debra Frost
Diana Eccles
Fiona Douglas
Jackie Cook
Julian Adlard
Julian Barwell
Lisa Walker
Louise Izatt
Lucy E. Side
M. John Kennedy
Marc Tischkowitz
Mark T. Rogers
Mary E. Porteous
Patrick J. Morrison
Radka Platte
Ros Eeles
Rosemarie Davidson
Shirley Hodgson
Trevor Cole
Andrew K Godwin
Claudine Isaacs
Kathleen Claes
Kim De Leeneer
Alfons Meindl
Andrea Gehrig
Barbara Wappenschmidt
Christian Sutter
Christoph Engel
Dieter Niederacher
Doris Steinemann
Hansjoerg Plendl
Karin Kast
Kerstin Rhiem
Nina Ditsch
Norbert Arnold
Raymonda Varon-Mateeva
Rita K. Schmutzler
Sabine Preisler-Adams
Nadja Bogdanova Markov
Shan Wang-Gohrke
Antoine de Pauw
Cedrick Lefol
Christine Lasset
Dominique Leroux
Etienne Rouleau
Francesca Damiola
Helene Dreyfus
Laure Barjhoux
Lisa Golmard
Nancy Uhrhammer
Valerie Bonadona
Valerie Sornin
Yves-Jean Bignon
Jonathan Carter
Linda Van Le
Marion Piedmonte
Paul A. DiSilvestro
Miguel de la Hoya
Trinidad Caldes
Heli Nevanlinna
Kristiina Aittomäki
Agnes Jager
Ans M. W. van den Ouweland
Carolien M. Kets
Cora M. Aalfs
Flora E. van Leeuwen
Frans B. L. Hogervorst
Hanne E. J. Meijers-Heijboer
Jan C. Oosterwijk
Kees E. P. van Roozendaal
Matti A. Rookus
Peter Devilee
Rob B. van der Luijt
Edith Olah
Orland Diez
Alex Teule
Conxi Lazaro
Ignacio Blanco
Jesus Del Valle
Anna Jakubowska
Grzegorz Sukiennicki
Jacek Gronwald
Amanda B. Spurdle
William Foulkes
Curtis Olswold
Noralene M. Lindor
Vernon S. Pankratz
Csilla I. Szabo
Anne Lincoln
Lauren Jacobs
Marina Corines
Mark Robson
Joseph Vijai
Andreas Berger
Anneliese Fink-Retter
Christian F. Singer
Christine Rappaport
Daphne Geschwantler Kaulich
Georg Pfeiler
Muy-Kheng Tea
Mark H. Greene
Phuong L. Mai
Gad Rennert
Evgeny N. Imyanitov
Anna Marie Mulligan
Gord Glendon
Irene L. Andrulis
Andrine Tchatchou
Amanda Ewart Toland
Inge Sokilde Pedersen
Mads Thomassen
Torben A. Kruse
Uffe Birk Jensen
Maria A. Caligo
Eitan Friedman
Jamal Zidan
Yael Laitman
Annika Lindblom
Beatrice Melin
Brita Arver
Niklas Loman
Richard Rosenquist
Olufunmilayo I. Olopade
Robert L. Nussbaum
Susan J. Ramus
Katherine L. Nathanson
Susan M. Domchek
Timothy R. Rebbeck
Banu K. Arun
Gillian Mitchell
Bethy Y. Karlan
Jenny Lester
Sandra Orsulic
Dominique Stoppa-Lyonnet
Gilles Thomas
Jacques Simard
Fergus J. Couch
Kenenth Offit
Douglas F. Easton
Georgia Chenevix-Trench
Antonis C. Antoniou
Sylvie Mazoyer
Catherine M. Phelan
Olga M. Sinilnikova
David G. Cox
eng
uncontrolled
single-nucleotide polymorphisms
eng
uncontrolled
genetic modifiers
eng
uncontrolled
oxidative stress
eng
uncontrolled
consortium
eng
uncontrolled
multiple diseases
eng
uncontrolled
DNA
eng
uncontrolled
haplogroups
eng
uncontrolled
susceptibility
eng
uncontrolled
Ovarian
eng
uncontrolled
variants
Krankheiten
open_access
Institut für Humangenetik
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14545/012_Blein_BREAST-CANCER-RESEARCH.pdf
22923
2020
eng
20
article
1
2021-03-03
--
--
Reduced hypertrophy in vitro after chondrogenic differentiation of adult human mesenchymal stem cells following adenoviral SOX9 gene delivery
Background
Mesenchymal stem cell (MSC) based-treatments of cartilage injury are promising but impaired by high levels of hypertrophy after chondrogenic induction with several bone morphogenetic protein superfamily members (BMPs). As an alternative, this study investigates the chondrogenic induction of MSCs via adenoviral gene-delivery of the transcription factor SOX9 alone or in combination with other inducers, and comparatively explores the levels of hypertrophy and end stage differentiation in a pellet culture system in vitro.
Methods
First generation adenoviral vectors encoding SOX9, TGFB1 or IGF1 were used alone or in combination to transduce human bone marrow-derived MSCs at 5 x 10\(^2\) infectious particles/cell. Thereafter cells were placed in aggregates and maintained for three weeks in chondrogenic medium. Transgene expression was determined at the protein level (ELISA/Western blot), and aggregates were analysed histologically, immunohistochemically, biochemically and by RT-PCR for chondrogenesis and hypertrophy.
Results
SOX9 cDNA was superior to that encoding TGFB1, the typical gold standard, as an inducer of chondrogenesis in primary MSCs as evidenced by improved lacuna formation, proteoglycan and collagen type II staining, increased levels of GAG synthesis, and expression of mRNAs associated with chondrogenesis. Moreover, SOX9 modified aggregates showed a markedly lower tendency to progress towards hypertrophy, as judged by expression of the hypertrophy markers alkaline phosphatase, and collagen type X at the mRNA and protein levels.
Conclusion
Adenoviral SOX9 gene transfer induces chondrogenic differentiation of human primary MSCs in pellet culture more effectively than TGFB1 gene transfer with lower levels of chondrocyte hypertrophy after 3 weeks of in vitro culture. Such technology might enable the formation of more stable hyaline cartilage repair tissues in vivo.
BMC Musculoskeletal Disorders
10.1186/s12891-020-3137-4
urn:nbn:de:bvb:20-opus-229232
publish
BMC Musculoskeletal Disorders (2020) 21:109 https://doi.org/10.1186/s12891-020-3137-4
true
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
M. Weissenberger
M. H. Weissenberger
F. Gilbert
J. Groll
C. H. Evans
A. F. Steinert
eng
uncontrolled
Mesenchymal stem cell
eng
uncontrolled
Cartilage
eng
uncontrolled
SOX9
eng
uncontrolled
Gene therapy
eng
uncontrolled
Chondrogenesis
eng
uncontrolled
Hypertrophy
eng
uncontrolled
Adenovirus
eng
uncontrolled
Bone marrow
Medizin und Gesundheit
open_access
Lehrstuhl für Orthopädie
Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie (Chirurgische Klinik II)
Abteilung für Funktionswerkstoffe der Medizin und der Zahnheilkunde
Förderzeitraum 2020
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/22923/s12891-020-3137-4.pdf
16686
2016
eng
e0158801
7
11
article
1
2018-08-08
--
--
Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10−16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10−6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
PLoS ONE
10.1371/journal.pone.0158801
urn:nbn:de:bvb:20-opus-166869
PLoS ONE 11(7):e0158801 (2016). DOI: 10.1371/journal.pone.0158801
false
true
CC 0: Public Domain Dedication
Elena Vigorito
Karoline B. Kuchenbaecker
Jonathan Beesley
Julian Adlard
Bjarni A. Agnarsson
Irene L. Andrulis
Banu K. Arun
Laure Barjhoux
Muriel Belotti
Javier Benitez
Andreas Berger
Anders Bojesen
Bernardo Bonanni
Carole Brewer
Trinidad Caldes
Maria A. Caligo
Ian Campbell
Salina B. Chan
Kathleen B. M. Claes
David E. Cohn
Jackie Cook
Mary B. Daly
Francesca Damiola
Rosemarie Davidson
Antoine de Pauw
Capucine Delnatte
Orland Diez
Susan M. Domchek
Martine Dumont
Katarzyna Durda
Bernd Dworniczak
Douglas F. Easton
Diana Eccles
Christina Edwinsdotter Ardnor
Ros Eeles
Bent Ejlertsen
Steve Ellis
D. Gareth Evans
Lidia Feliubadalo
Florentia Fostira
William D. Foulkes
Eitan Friedman
Debra Frost
Pragna Gaddam
Patricia A. Ganz
Judy Garber
Vanesa Garcia-Barberan
Marion Gauthier-Villars
Andrea Gehrig
Anne-Marie Gerdes
Sophie Giraud
Andrew K. Godwin
David E. Goldgar
Christopher R. Hake
Thomas V. O. Hansen
Sue Healey
Shirley Hodgson
Frans B. L. Hogervorst
Claude Houdayer
Peter J. Hulick
Evgeny N. Imyanitov
Claudine Isaacs
Louise Izatt
Angel Izquierdo
Lauren Jacobs
Anna Jakubowska
Ramunas Janavicius
Katarzyna Jaworska-Bieniek
Uffe Birk Jensen
Esther M. John
Joseph Vijai
Beth Y. Karlan
Karin Kast
Sofia Khan
Ava Kwong
Yael Laitman
Jenny Lester
Fabienne Lesueur
Annelie Liljegren
Jan Lubinski
Phuong L. Mai
Siranoush Manoukian
Sylvie Mazoyer
Alfons Meindl
Arjen R. Mensenkamp
Marco Montagna
Katherine L. Nathanson
Susan L. Neuhausen
Heli Nevanlinna
Dieter Niederacher
Edith Olah
Olufunmilayo I. Olopade
Kai-ren Ong
Ana Osorio
Sue Kyung Park
Ylva Paulsson-Karlsson
Inge Sokilde Pedersen
Bernard Peissel
Paolo Peterlongo
Georg Pfeiler
Catherine M. Phelan
Marion Piedmonte
Bruce Poppe
Miquel Angel Pujana
Paolo Radice
Gad Rennert
Gustavo C. Rodriguez
Matti A. Rookus
Eric A. Ross
Rita Katharina Schmutzler
Jacques Simard
Christian F. Singer
Thomas P. Slavin
Penny Soucy
Melissa Southey
Doris Steinemann
Dominique Stoppa-Lyonnet
Grzegorz Sukiennicki
Christian Sutter
Csilla I. Szabo
Muy-Kheng Tea
Manuel R. Teixeira
Soo-Hwang Teo
Mary Beth Terry
Mads Thomassen
Maria Grazia Tibiletti
Laima Tihomirova
Silvia Tognazzo
Elizabeth J. van Rensburg
Liliana Varesco
Raymonda Varon-Mateeva
Athanassios Vratimos
Jeffrey N. Weitzel
Lesley McGuffog
Judy Kirk
Amanda Ewart Toland
Ute Hamann
Noralane Lindor
Susan J. Ramus
Mark H. Greene
Fergus J. Couch
Kenneth Offit
Paul D. P. Pharoah
Georgia Chenevix-Trench
Antonis C. Antoniou
eng
uncontrolled
fine-scale mapping
eng
uncontrolled
ovarian cancer
eng
uncontrolled
genetics
eng
uncontrolled
BRCA1
eng
uncontrolled
BRCA2
Medizin und Gesundheit
open_access
Institut für Humangenetik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16686/Vigorito_PLoS_ONE.PDF
16476
2016
eng
15
18
article
1
2018-07-17
--
--
Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2
Background
BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs).
Methods
We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database.
Results
Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10−5) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor–positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15–21.80] and progesterone receptor–positive (OR 5.04; 95 % CI 3.17–8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10−12).
Conclusions
On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.
Breast Cancer Research
10.1186/s13058-016-0671-y
urn:nbn:de:bvb:20-opus-164769
Breast Cancer Research (2016) 18:15
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Valentina Silvestri
Daniel Barrowdale
Anna Marie Mulligan
Susan L. Neuhausen
Stephen Fox
Beth Y. Karlan
Gillian Mitchell
Paul James
Darcy L. Thull
Kristin K. Zorn
Natalie J. Carter
Katherine L. Nathanson
Susan M. Domchek
Timothy R. Rebbeck
Susan J. Ramus
Robert L. Nussbaum
Olufunmilayo I. Olopade
Johanna Rantala
Sook-Yee Yoon
Maria A. Caligo
Laura Spugnesi
Anders Bojesen
Inge Sokilde Pedersen
Mads Thomassen
Uffe Birk Jensen
Amanda Ewart Toland
Leigha Senter
Irene L. Andrulis
Gord Glendon
Peter J. Hulick
Evgeny N. Imyanitov
Mark H. Greene
Phuong L. Mai
Christian F. Singer
Christine Rappaport-Fuerhauser
Gero Kramer
Joseph Vijai
Kenneth Offit
Mark Robson
Anne Lincoln
Lauren Jacobs
Eva Machackova
Lenka Foretova
Marie Navratilova
Petra Vasickova
Fergus J. Couch
Emily Hallberg
Kathryn J. Ruddy
Priyanka Sharma
Sung-Won Kim
Manuel R. Teixeira
Pedro Pinto
Marco Montagna
Laura Matricardi
Adalgeir Arason
Oskar Th Johannsson
Rosa B. Barkardottir
Anna Jakubowska
Jan Lubinski
Angel Izquierdo
Miguel Angel Pujana
Judith Balmaña
Orland Diez
Gabriella Ivady
Janos Papp
Edith Olah
Ava Kwong
Heli Nevanlinna
Kristiina Aittomäki
Pedro Perez Segura
Trinidad Caldes
Tom Van Maerken
Bruce Poppe
Kathleen B. M. Claes
Claudine Isaacs
Camille Elan
Christine Lasset
Dominique Stoppa-Lyonnet
Laure Barjhoux
Muriel Belotti
Alfons Meindl
Andrea Gehrig
Christian Sutter
Christoph Engel
Dieter Niederacher
Doris Steinemann
Eric Hahnen
Karin Kast
Norbert Arnold
Raymonda Varon-Mateeva
Dorothea Wand
Andrew K. Godwin
D. Gareth Evans
Debra Frost
Jo Perkins
Julian Adlard
Louise Izatt
Radka Platte
Ros Eeles
Steve Ellis
Ute Hamann
Judy Garber
Florentia Fostira
George Fountzilas
Barbara Pasini
Giuseppe Giannini
Piera Rizzolo
Antonio Russo
Laura Cortesi
Laura Papi
Liliana Varesco
Domenico Palli
Ines Zanna
Antonella Savarese
Paolo Radice
Siranoush Manoukian
Bernard Peissel
Monica Barile
Bernardo Bonanni
Alessandra Viel
Valeria Pensotti
Stefania Tommasi
Paolo Peterlongo
Jeffrey N. Weitzel
Ana Osorio
Javier Benitez
Lesley McGuffog
Sue Healey
Anne-Marie Gerdes
Bent Ejlertsen
Thomas V. O. Hansen
Linda Steele
Yuan Chun Ding
Nadine Tung
Ramunas Janavicius
David E. Goldgar
Saundra S. Buys
Mary B. Daly
Anita Bane
Mary Beth Terry
Esther M. John
Melissa Southey
Douglas F. Easton
Georgia Chenevix-Trench
Antonis C. Antoniou
Laura Ottini
eng
uncontrolled
Male breast cancer
eng
uncontrolled
BRCA1/2
eng
uncontrolled
Pathology
eng
uncontrolled
Histologic grade
eng
uncontrolled
Genotype–phenotype correlations
Induktion
open_access
Institut für Humangenetik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16476/028_Silvestri_BREAST-CANCER-RESEARCH.pdf