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
16686
2016
eng
e0158801
7
11
article
1
2018-08-08
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--
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