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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
Communications Biology, Volume 5, No. 1, Article 1061, Year 2022
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Description
The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09–1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers. © 2022, The Author(s).
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC9537519/bin/42003_2022_3978_MOESM1_ESM.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC9537519/bin/42003_2022_3978_MOESM2_ESM.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC9537519/bin/42003_2022_3978_MOESM3_ESM.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC9537519/bin/42003_2022_3978_MOESM4_ESM.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC9537519/bin/42003_2022_3978_MOESM5_ESM.pdf
Authors & Co-Authors
Marquart-Wilson, Louise
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Australia, Brisbane
The University of Queensland
Dennis, Joe G.
United Kingdom, Cambridge
University of Cambridge
Barnes, Daniel R.
United Kingdom, Cambridge
University of Cambridge
Robinson, Bridget Anne
New Zealand, Christchurch
University of Otago, Christchurch
New Zealand, Christchurch
Canterbury District Health Board
Aittomäki, Kristiina
Finland, Helsinki
Helsingin Yliopisto
Andrulis, Irene L.
Canada, Toronto
Mount Sinai Hospital of University of Toronto
Canada, Toronto
University of Toronto
Azzollini, Jacopo
Italy, Milan
Fondazione Irccs Istituto Nazionale Dei Tumori, Milan
Balmaña, Judith
Spain, Barcelona
Vall D‘hebron Institut de Oncologia
Spain, Barcelona
Hospital Universitari de Bellvitge
Barkardóttir, Rósa Björk
Iceland, Reykjavik
Landspitali - the National University Hospital of Iceland
Iceland, Reykjavik
Haskoli Islands
Blok, Marinus J.
Netherlands, Maastricht
Maastricht Universitair Medisch Centrum+
Boonen, Susanne Eriksen
Denmark, Odense
Odense Universitetshospital
Borde, Julika
Germany, Aachen
Centrum Für Integrierte Onkologie
Germany, Koln
Universität zu Köln
Bradbury, Angela R.
United States, Philadelphia
University of Pennsylvania Perelman School of Medicine
Brunet, Joan Maria
Spain, Hospitalet de Llobregat
Institut D'investigació Biomedica de Bellvitge
Caligo, Maria Adelaide
Italy, Pisa
Azienda Ospedaliero Universitaria Pisana
Campbell, I. G. G.
Australia, Melbourne
Peter Maccallum Cancer Centre
Chung, Wendy Kay
United States, New York
Columbia University
Claes, Kathleen B.M.
Belgium, Ghent
Universitair Ziekenhuis Gent
Collonge-Rame, Marie Agnès
France, Besancon
Centre Hospitalier Universitaire de Besançon
Cook, Jacqueline A.
United Kingdom, Sheffield
Sheffield Children's Hospital
Couch, Fergus J.
United States, Rochester
Mayo Clinic
Daly, Mary B.
United States, Philadelphia
Fox Chase Cancer Center
Davidson, Rosemarie H.
United Kingdom, Glasgow
Queen Elizabeth University Hospital, Glasgow
de la Hoya, Miguel
Spain, Madrid
Centro de Investigación Biomédica en Red de Cáncer
de Putter, Robin
Belgium, Ghent
Universitair Ziekenhuis Gent
Delnatte, Capucine D.
France, Saint-herblain
Institut de Cancérologie de L'ouest René-gauducheau
Díez, Orland
Spain, Barcelona
Vall D‘hebron Institut de Oncologia
Spain, Barcelona
Hospital Universitari de Bellvitge
Ding, Yuanchun
United States, Duarte
City of Hope National Med Center
Domchek, Susan M.
United States, Philadelphia
University of Pennsylvania
Donaldson, Alan
United Kingdom, Bristol
St. Michael's Hospital
Eason, Jacqueline
United Kingdom, Nottingham
Nottingham University Hospitals Nhs Trust
Easton, Douglas F.
United Kingdom, Cambridge
University of Cambridge
Ehrencrona, Hans
Sweden, Lund
Skånes Universitetssjukhus
Sweden, Lund
Lunds Universitet
Engel, Christoph
Germany, Leipzig
Universität Leipzig
Evans, D. Gareth R.
United Kingdom, Manchester
Health Innovation Manchester
United Kingdom, Manchester
Manchester University Nhs Foundation Trust
Faust, Ulrike E.A.
Germany, Tubingen
Eberhard Karls Universität Tübingen
Feliubadaló, Lidia
Spain, Hospitalet de Llobregat
Institut D'investigació Biomedica de Bellvitge
Fostira, Florentia
Greece, Athens
National Centre for Scientific Research Demokritos
Friedman, Eitan A.
Israel, Tel Hashomer Tel Aviv
Chaim Sheba Medical Center Israel
Israel, Tel Aviv-yafo
Tel Aviv University
Frost, Debra
United Kingdom, Cambridge
University of Cambridge
Garber, Judy Ellen
United States, Boston
Dana-farber Cancer Institute
Gayther, Simon A.
United States, Los Angeles
Cedars-sinai Medical Center
Gehrig, Andrea E.
Germany, Wurzburg
Julius-maximilians-universität Würzburg
Gesta, Paul H.
France, Niort
Ch de Niort
Goldgar, David E.
United States, Salt Lake City
University of Utah School of Medicine
Greene, Mark H.
United States, Rockville
National Cancer Institute Nci
Hahnen, Eric T.
Germany, Aachen
Centrum Für Integrierte Onkologie
Germany, Koln
Universität zu Köln
Hamann, Ute
Germany, Heidelberg
German Cancer Research Center
Hauke, Jan
Germany, Aachen
Centrum Für Integrierte Onkologie
Germany, Koln
Universität zu Köln
Hentschel, Julia
Germany, Leipzig
Universitätsklinikum Leipzig Und Medizinische Fakultät
Honisch, Ellen
Germany, Dusseldorf
Heinrich-heine-universität Düsseldorf
Hulick, Peter J.
United States, Evanston
Northshore University Healthsystem
United States, Chicago
Pritzker School of Medicine
Isaacs, Claudine J.
United States, Washington, D.c.
Georgetown University
Izatt, Louise
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
Izquierdo, Ángel J.
Spain, Hospitalet de Llobregat
Institut D'investigació Biomedica de Bellvitge
Jakubowska, Anna
Poland, Szczecin
Pomeranian Medical University in Szczecin
James, Paul A.
Australia, Melbourne
Peter Maccallum Cancer Centre
Janavičius, Ramūnas
Lithuania, Vilnius
Vilniaus Universitetas
John, Esther M.
United States, Stanford
Stanford University School of Medicine
United States, Stanford
Stanford Cancer Institute
Karlan, Beth Y.
United States, Los Angeles
University of California, Los Angeles
Kemp, Zoe E.
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
Konstantopoulou, Irene
Greece, Athens
National Centre for Scientific Research Demokritos
Laitman, Yael
Israel, Tel Hashomer Tel Aviv
Chaim Sheba Medical Center Israel
Lalloo, Fiona I.
United States, New York
Weill Cornell Medicine
Lasset, Christine
France, Lyon
Le Centre Régional de Lutte Contre le Cancer Léon Bérard
Lázaro, Conxi
Spain, Hospitalet de Llobregat
Institut D'investigació Biomedica de Bellvitge
Leslie, Goska
United Kingdom, Cambridge
University of Cambridge
Lesueur, Fabienne El Khoury
France, Paris
Cancer et Génome : Bioinformatique, Biostatistiques et Épidémiologie Des Systèmes Complexes
France, Paris
Institut Curie
France, Paris
Mines Paris - Psl
Mai, Phuong L.
United States, Pittsburgh
University of Pittsburgh School of Medicine
Mari, Véronique
France, Nice
Centre Antoine Lacassagne
Martens, J. W. M. W.M.
Netherlands, Rotterdam
Erasmus Mc Cancer Institute
McGuffog, Lesley
United Kingdom, Cambridge
University of Cambridge
Mebirouk, Noura
France, Paris
Cancer et Génome : Bioinformatique, Biostatistiques et Épidémiologie Des Systèmes Complexes
France, Paris
Institut Curie
France, Paris
Mines Paris - Psl
Meindl, Alfons
Germany, Munich
Ludwig-maximilians-universität München
Miller, Austin
United States, Buffalo
Roswell Park Cancer Institute
Mouret-Fourme, Emmanuelle
France, Paris
Institut Curie
Nambot, Sophie
France, Dijon
Centre Georges-françois Leclerc
Nathanson, Katherine L.
United States, Philadelphia
University of Pennsylvania
Floris, Giuseppe L.
United States, Duarte
City of Hope National Med Center
Nevanlinna, Heli A.
Finland, Helsinki
Helsingin Yliopisto
Offit, Kenneth
United States, New York
Memorial Sloan-kettering Cancer Center
Oláh, Edith
Hungary, Budapest
Országos Onkológiai Intézet Budapest
Olopade, Olufunmilayo Ibironke
United States, Chicago
The University of Chicago
Osorio, Ana
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Raras
Ott, Claus Eric
Germany, Berlin
Freie Universität Berlin
Park, Suekyung
South Korea, Seoul
Seoul National University College of Medicine
South Korea, Seoul
Seoul National University
Parsons, Michael T.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Pedersen, Inge Søkilde
Denmark, Aalborg
Aalborg Universitetshospital
Denmark, Aalborg
Aalborg University
Peterlongo, Paolo
Italy, Milan
Fondazione Ifom Istituto Firc Di Oncologia Molecolare
Rantala, Johanna
Sweden, Stockholm
Karolinska Institutet
Rodríguez, Gustavo C.
United States, Chicago
The University of Chicago
Rossing, Maria Caroline
Denmark, Copenhagen
Rigshospitalet
Denmark, Copenhagen
Københavns Universitet
Schmutzler, Rita Katharina
Germany, Aachen
Centrum Für Integrierte Onkologie
Germany, Koln
Universität zu Köln
Shah, Payal Deepak
United States, Philadelphia
University of Pennsylvania Perelman School of Medicine
Sharma, Priyanka
United States, Kansas City
University of Kansas Medical Center
Side, Lucy E.
United Kingdom, Southampton
Princess Anne Hospital
Singer, Christian Fridolin
Austria, Vienna
Medizinische Universität Wien
Snape, Katie M.G.
United Kingdom, London
St George’s, University of London
Steinemann, Doris
Germany, Hannover
Hannover Medical School
Stoppa-Lyonnet, Dominique
France, Paris
Institut Curie
France, Paris
Cancer, Hétérogénéité, Instabilité et Plasticité Chip
France, Paris
Université Paris Cité
Sutter, Christian
Germany, Heidelberg
Universitätsklinikum Heidelberg
Teixeira, Manuel R.
Portugal, Porto
Instituto Português de Oncologia do Porto fg
Portugal, Porto
Universidade do Porto
Teo, Soo Hwang
Malaysia, Kuala Lumpur
Universiti Malaya
Thomassen, Mads Christella L.G.D.
Denmark, Odense
Odense Universitetshospital
Tischkowitz, Marc D.
Canada, Montreal
Université Mcgill
United Kingdom, Royston
National Institute for Health and Care Research
Tung, Nadine M.
United States, Boston
Beth Israel Deaconess Medical Center
van Rensburg, Elizabeth J.
South Africa, Pretoria
University of Pretoria
Vega, Ana Karina
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Raras
Spain, Santiago de Compostela
Fundación Pública Galega de Medicina Xenómica
Spain, Santiago de Compostela
Instituto de Investigación Sanitaria de Santiago de Compostela
Walker, Lisa J.
United Kingdom, Oxford
Churchill Hospital
Weitzel, Jeffrey Nelson
Unknown Affiliation
Antoniou, Antonis C.
United Kingdom, Cambridge
University of Cambridge
Walker, Logan C.
New Zealand, Christchurch
University of Otago, Christchurch
Statistics
Citations: 1
Authors: 112
Affiliations: 131
Identifiers
Doi:
10.1038/s42003-022-03978-6
ISSN:
23993642
Research Areas
Cancer
Environmental
Genetics And Genomics