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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers
Human Mutation, Volume 33, No. 4, Year 2012
Notification
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Description
Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 × 10-4, rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 × 10-4, rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 × 10-4. The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer. © 2012 Wiley Periodicals, Inc.
Authors & Co-Authors
Ramus, Susan J.
United States, Los Angeles
University of Southern California
Antoniou, Antonis C.
United Kingdom, Cambridge
University of Cambridge
Kuchenbaecker, Karoline B.
United Kingdom, Cambridge
University of Cambridge
Soucy, Penny
Canada, Quebec
Université Laval
Beesley, Jonathan
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Chen, Xiaoqing
Australia, Brisbane
Qimr Berghofer Medical Research Institute
McGuffog, Lesley
United Kingdom, Cambridge
University of Cambridge
Sinilnikova, Olga M.
France, Lyon
Le Centre Régional de Lutte Contre le Cancer Léon Bérard
France, Villeurbanne
Université Claude Bernard Lyon 1
Healey, Sue C.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Barrowdale, Daniel
United Kingdom, Cambridge
University of Cambridge
Lee, Andrew J.
United Kingdom, Cambridge
University of Cambridge
Thomassen, Mads Christella L.G.D.
Denmark, Odense
Odense Universitetshospital
Gerdes, Anne Marie Axø
Denmark, Copenhagen
Rigshospitalet
Kruse, Torben Arvid
Denmark, Odense
Odense Universitetshospital
Jensen, Uffe Birk
Denmark, Aarhus
Aarhus Universitetshospital
Caligo, Maria Adelaide
Italy, Pisa
Azienda Ospedaliero Universitaria Pisana
Liljegren, Annelie
Sweden, Stockholm
Karolinska Universitetssjukhuset
Lindblöm, Annika
Sweden, Stockholm
Karolinska Universitetssjukhuset
Kristoffersson, Ulf
Sweden, Lund
Skånes Universitetssjukhus
Stenmark-Askmalm, Marie
Sweden, Linkoping
Linköpings Universitet
Domchek, Susan M.
United States, Philadelphia
University of Pennsylvania
Nathanson, Katherine L.
United States, Philadelphia
University of Pennsylvania
Rebbeck, Timothy Richard
United States, Philadelphia
University of Pennsylvania
Jakubowska, Anna
Poland, Szczecin
Pomeranian Medical University in Szczecin
Lubiński, Jan
Poland, Szczecin
Pomeranian Medical University in Szczecin
Durda, Katarzyna M.
Poland, Szczecin
Pomeranian Medical University in Szczecin
Gronwald, Jacek
Poland, Szczecin
Pomeranian Medical University in Szczecin
Huzarski, Tomasz
Poland, Szczecin
Pomeranian Medical University in Szczecin
Cybulski, Cezary
Poland, Szczecin
Pomeranian Medical University in Szczecin
Tołoczko-Grabarek, Aleksandra Izabela
Poland, Szczecin
Pomeranian Medical University in Szczecin
Osorio, Ana
Spain, Madrid
Centro Nacional de Investigaciones Oncológicas
Benit́ez, Javier J.
Spain, Madrid
Centro Nacional de Investigaciones Oncológicas
Durán, Mercedes
Spain, Valladolid
Csic-uva - Instituto de Biologia y Genetica Molecular Ibgm
Tejada, María Isabel
Spain, Baracaldo
Osakidetza, Cruces University Hospital
Hamann, Ute
Germany, Heidelberg
German Cancer Research Center
Rookus, Matti A.
Netherlands, Amsterdam
The Netherlands Cancer Institute
van Leeuwen, Flora Elizabeth
Netherlands, Amsterdam
The Netherlands Cancer Institute
Aalfs, Cora M.
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Meijers-Heijboer, Hanne E.J.
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
van Asperen, Christi J.
Netherlands, Leiden
Universiteit Leiden
Hoogerbrugge, Nicoline
Netherlands, Nijmegen
Radboud University Medical Center
Collée, Johanna Margriet
Netherlands, Rotterdam
Erasmus Mc
Kriege, Mieke G.
Netherlands, Rotterdam
Erasmus Mc
van der Luijt, Rob B.
Netherlands, Utrecht
University Medical Center Utrecht
Peock, Susan
United Kingdom, Cambridge
University of Cambridge
Frost, Debra
United Kingdom, Cambridge
University of Cambridge
Ellis, Steve D.
United Kingdom, Cambridge
University of Cambridge
Platte, Radka
United Kingdom, Cambridge
University of Cambridge
Fineberg, Elena
United Kingdom, Cambridge
University of Cambridge
Evans, D. Gareth R.
United Kingdom, Manchester
Manchester University Nhs Foundation Trust
Lalloo, Fiona I.
United Kingdom, Manchester
Manchester University Nhs Foundation Trust
Jacobs, Chris
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
Eeles, Ros A.
United Kingdom, London
The Institute of Cancer Research
Adlard, Julian W.
United Kingdom, Leeds
Yorkshire Regional Genetics Service
Davidson, Rosemarie H.
United Kingdom, Glasgow
Royal Hospital for Sick Children
Eccles, Diana M.
United Kingdom, Southampton
University Hospital Southampton Nhs Foundation Trust
Cole, Trevor R.P.
United Kingdom, Birmingham
Birmingham Women’s and Children’s Nhs Foundation Trust
Cook, Jacqueline A.
United Kingdom, Sheffield
Sheffield Children's Hospital
Paterson, Joan S.
United Kingdom, Cambridge
Addenbrooke's Hospital
Douglas, Fiona S.
United Kingdom, Newcastle
University of Newcastle Upon Tyne, Faculty of Medical Sciences
Brewer, Carole M.
United Kingdom, Exeter
Royal Devon and Exeter Hospital
Hodgson, Shirley Victoria
United Kingdom, London
St George’s, University of London
Morrison, Patrick J.
United Kingdom, Belfast
Belfast Health and Social Care Trust
Walker, Lisa J.
United Kingdom, Oxford
Churchill Hospital
Porteous, Mary E.M.
United Kingdom, Edinburgh
Western General Hospital
Kennedy, Michael John
Ireland, Dublin
Trinity College Dublin
Pathak, Harsh B.
United States, Kansas City
University of Kansas Medical Center
Godwin, Andrew K.
United States, Kansas City
University of Kansas Medical Center
Stoppa-Lyonnet, Dominique
France, Paris
Institut Curie
France, Paris
Université Paris Cité
Caux-Moncoutier, Virginie
France, Paris
Institut Curie
de Pauw, Antoine
France, Paris
Institut Curie
Gauthier-Villars, Marion
France, Paris
Institut Curie
Mazoyer, Sylvie
France, Villeurbanne
Université Claude Bernard Lyon 1
Léoné, Meĺanie
France, Lyon
Le Centre Régional de Lutte Contre le Cancer Léon Bérard
Calender, Alain
France, Lyon
Le Centre Régional de Lutte Contre le Cancer Léon Bérard
Lasset, Christine
France, Villeurbanne
Laboratoire de Biométrie et Biologie Évolutive
France, Lyon
Le Centre Régional de Lutte Contre le Cancer Léon Bérard
Bonadona, Valérie
France, Villeurbanne
Laboratoire de Biométrie et Biologie Évolutive
France, Lyon
Le Centre Régional de Lutte Contre le Cancer Léon Bérard
Hardouin, Agnès
France, Caen
Centre François Baclesse
Berthet, Pascaline
France, Caen
Centre François Baclesse
Bignon, Yves Jean
France, Clermont-ferrand
Université Clermont Auvergne
Uhrhammer, Nancy A.
France, Clermont-ferrand
Université Clermont Auvergne
Faivre, Laurence
France, Dijon
Centre Hospitalier Universitaire Dijon Bourgogne
France, Dijon
Centre Georges-françois Leclerc
Buys, Saundra S.
United States, Salt Lake City
The University of Utah
Daly, Mary B.
United States, Philadelphia
Fox Chase Cancer Center
Miron, Alexander F.
United States, Boston
Dana-farber Cancer Institute
Chung, Wendy Kay
United States, New York
Columbia University
John, Esther M.
United States, Fremont
Cancer Prevention Institute of California
Southey, Melissa Caroline
Australia, Melbourne
University of Melbourne
Goldgar, David F.
United States, Salt Lake City
University of Utah School of Medicine
Singer, Christian Fridolin
Unknown Affiliation
Pfeiler, Georg
Unknown Affiliation
Hansen, Thomas Van Overeem
Denmark, Copenhagen
Copenhagen University Hospital
Ejlertsen, Bent
Denmark, Copenhagen
Copenhagen University Hospital
Jóhannsson, Óskar Th
Iceland, Reykjavik
Haskoli Islands
Offit, Kenneth
United States, New York
Memorial Sloan-kettering Cancer Center
Kirchhoff, Tomas
United States, New York
Nyu Langone Health
Gaudet, Mia M.
United States, Kennesaw
American Cancer Society
Robson, Mark E.
United States, New York
Memorial Sloan-kettering Cancer Center
Piedmonte, Marion R.
Unknown Affiliation
Phillips, K. A.
Australia, Melbourne
Peter Maccallum Cancer Centre
van Le, Linda
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Toland, Amanda Ewart
United States, Columbus
The Ohio State University
Montagna, Marco
Italy, Padua
Istituto Oncologico Veneto Iov - Irccs
Imyanitov, Evgeny N.
Russian Federation, Saint Petersburg
N.n. Petrov Research Institute of Oncology of the Ussr Ministry of Health
Isaacs, Claudine J.D.
United States, Washington, D.c.
Georgetown University
Janavičius, Ramūnas
Lithuania, Vilnius
Vilniaus Universitetas
Lázaro, Conxi
Unknown Affiliation
Blanco, Ignacio
Unknown Affiliation
Navarro, Matilde Y.
Unknown Affiliation
Moysich, Kirsten Barbara
United States, Buffalo
Roswell Park Cancer Institute
Karlan, Beth Y.
United States, Los Angeles
Cedars-sinai Medical Center
Oláh, Edith
Hungary, Budapest
Országos Onkológiai Intézet Budapest
Teo, Soo Hwang
Malaysia, Subang Jaya
Cancer Reserach Initiatives Foundation, Malaysia
Ganz, Patricia A.
United States, Los Angeles
David Geffen School of Medicine at Ucla
Beattie, Mary Spanos
United States, San Francisco
University of California, San Francisco
Dorfling, Cecilia M.
South Africa, Pretoria
University of Pretoria
van Rensburg, Elizabeth J.
South Africa, Pretoria
University of Pretoria
Díez, Orland
Spain, Barcelona
Hospital Universitari Vall D'hebron
Kwong, Ava
China, Hong Kong
Hong Kong Sanatorium and Hospital
Schmutzler, Rita Katharina
Germany, Koln
Uniklinik Köln
Wappenschmidt, Barbara
Germany, Koln
Uniklinik Köln
Engel, Christoph
Germany, Leipzig
Universität Leipzig
Meindl, Alfons
Germany, Munich
Technische Universität München
Ditsch, Nina
Germany, Munich
Ludwig-maximilians-universität München
Arnold, Norbert K.
Germany, Kiel
Christian-albrechts-universität zu Kiel
Niederacher, Dieter
Germany, Dusseldorf
Heinrich-heine-universität Düsseldorf
Preisler-Adams, Sabine S.
Germany, Munster
University of Münster
Gadzicki, Dorothea
Germany, Hannover
Hannover Medical School
Varon-Mateeva, Raymonda
Germany, Berlin
Charité – Universitätsmedizin Berlin
Gehrig, Andrea E.
Germany, Wurzburg
Julius-maximilians-universität Würzburg
Sutter, Christian
Germany, Heidelberg
Universitätsklinikum Heidelberg
Kast, Karin
Germany, Dresden
Technische Universität Dresden
Fiebig, Britta S.
Germany, Regensburg
Universität Regensburg
Caldés, Trinidad
Spain, Madrid
Hospital Clínico San Carlos
de la Hoya, Miguel
Spain, Madrid
Hospital Clínico San Carlos
Nevanlinna, Heli A.
Finland, Helsinki
Helsingin Yliopisto
Aittomäki, Kristiina A.U.
Finland, Helsinki
Helsinki University Hospital
Plante, Marie
Canada, Quebec
Chu de Québec-université Laval
Spurdle, Amanda B.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Floris, Giuseppe L.
United States, Duarte
City of Hope National Med Center
Ding, Yuanchun
United States, Duarte
City of Hope National Med Center
Wang, Xianshu
United States, Rochester
Mayo Clinic
Lindor, Noralane M.
United States, Rochester
Mayo Clinic
Fredericksen, Zachary S.
United States, Rochester
Mayo Clinic
Pankratz, Vernon Shane
United States, Rochester
Mayo Clinic
Peterlongo, Paolo
Italy, Milan
Fondazione Irccs Istituto Nazionale Dei Tumori, Milan
Italy, Milan
Fondazione Ifom Istituto Firc Di Oncologia Molecolare
Manoukian, Siranoush
Italy, Milan
Fondazione Irccs Istituto Nazionale Dei Tumori, Milan
Zaffaroni, Daniela
Italy, Milan
Fondazione Irccs Istituto Nazionale Dei Tumori, Milan
Bonanni, Bernardo
Italy, Milan
Istituto Europeo Di Oncologia
Bernard, Loris
Italy, Milan
Istituto Europeo Di Oncologia
Dolcetti, Riccardo
Italy, Aviano
Irccs Centro Di Riferimento Oncologico Aviano
Papi, Laura
Italy, Florence
Università Degli Studi Di Firenze
Ottini, Laura
Italy, Rome
Sapienza Università Di Roma
Radice, Paolo
Italy, Milan
Fondazione Irccs Istituto Nazionale Dei Tumori, Milan
Italy, Milan
Fondazione Ifom Istituto Firc Di Oncologia Molecolare
Greene, Mark H.
United States, Bethesda
National Institutes of Health Nih
Mai, Phuong L.
United States, Bethesda
National Institutes of Health Nih
Andrulis, Irene L.L.
Canada, Toronto
The Lunenfeld-tanenbaum Research Institute of University of Toronto
Glendon, Gord
Canada, Toronto
Cancer Care Ontario
Özçelik, Hilmi
Canada, Toronto
The Lunenfeld-tanenbaum Research Institute of University of Toronto
Pharoah, Paul D.P.
United Kingdom, Cambridge
University of Cambridge
Gayther, Simon A.
United States, Los Angeles
University of Southern California
Simard, Jacques
Canada, Quebec
Université Laval
d'Adamo, Adamo P.
United Kingdom, Cambridge
University of Cambridge
Couch, Fergus J.
United States, Rochester
Mayo Clinic
Chenevix-Trench, Georgia
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Statistics
Citations: 33
Authors: 165
Affiliations: 111
Identifiers
Doi:
10.1002/humu.22025
ISSN:
10597794
Research Areas
Cancer
Environmental
Genetics And Genomics
Study Design
Cross Sectional Study
Cohort Study
Case-Control Study
Participants Gender
Female