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Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Lookup NU author(s): Dr Fiona Douglas

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Abstract

Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 x 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05-1.29; P = 3.8 x 10(-4)) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10-1.52; P = 1.8 x 10(-3)). Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(4); 645-57. (C) 2012 AACR.


Publication metadata

Author(s): Couch FJ, Gaudet MM, Antoniou AC, Ramus SJ, Kuchenbaecker KB, Soucy P, Beesley J, Chen XQ, Wang XS, Kirchhoff T, McGuffog L, Barrowdale D, Lee A, Healey S, Sinilnikova OM, Andrulis IL, Ozcelik H, Mulligan AM, Thomassen M, Gerdes AM, Jensen UB, Skytte AB, Kruse TA, Caligo MA, von Wachenfeldt A, Barbany-Bustinza G, Loman N, Soller M, Ehrencrona H, Karlsson P, Nathanson KL, Rebbeck TR, Domchek SM, Jakubowska A, Lubinski J, Jaworska K, Durda K, Zlowocka E, Huzarski T, Byrski T, Gronwald J, Cybulski C, Gorski B, Osorio A, Duran M, Tejada MI, Benitez J, Hamann U, Hogervorst FBL, van Os TA, van Leeuwen FE, Meijers-Heijboer HEJ, Wijnen J, Blok MJ, Kets M, Hooning MJ, Oldenburg RA, Ausems MGEM, Peock S, Frost D, Ellis SD, Platte R, Fineberg E, Evans DG, Jacobs C, Eeles RA, Adlard J, Davidson R, Eccles DM, Cole T, Cook J, Paterson J, Brewer C, Douglas F, Hodgson SV, Morrison PJ, Walker L, Porteous ME, Kennedy MJ, Side LE, Bove B, Godwin AK, Stoppa-Lyonnet D, Fassy-Colcombet M, Castera L, Cornelis F, Mazoyer S, Leone M, Boutry-Kryza N, Bressac-de Paillerets B, Caron O, Pujol P, Coupier I, Delnatte C, Akloul L, Lynch HT, Snyder CL, Buys SS, Daly MB, Terry M, Chung WK, John EM, Miron A, Southey MC, Hopper JL, Goldgar DE, Singer CF, Rappaport C, Tea MKM, Fink-Retter A, Hansen TVO, Nielsen FC, Arason A, Vijai J, Shah S, Sarrel K, Robson ME, Piedmonte M, Phillips K, Basil J, Rubinstein WS, Boggess J, Wakeley K, Ewart-Toland A, Montagna M, Agata S, Imyanitov EN, Isaacs C, Janavicius R, Lazaro C, Blanco I, Feliubadalo L, Brunet J, Gayther SA, Pharoah PPD, Odunsi KO, Karlan BY, Walsh CS, Olah E, Teo SH, Ganz PA, Beattie MS, van Rensburg EJ, Dorfling CM, Diez O, Kwong A, Schmutzler RK, Wappenschmidt B, Engel C, Meindl A, Ditsch N, Arnold N, Heidemann S, Niederacher D, Preisler-Adams S, Gadzicki D, Varon-Mateeva R, Deissler H, Gehrig A, Sutter C, Kast K, Fiebig B, Heinritz W, Caldes T, de la Hoya M, Muranen TA, Nevanlinna H, Tischkowitz M, Spurdle AB, Neuhausen SL, Ding YC, Lindor NM, Fredericksen Z, Pankratz VS, Peterlongo P, Manoukian S, Peissel B, Zaffaroni D, Barile M, Bernard L, Viel A, Giannini G, Varesco L, Radice P, Greene MH, Mai PL, Easton DF, Chenevix-Trench G, Offit K, Simard J, OCGN, SWE-BRCA, HEBON, EMBRACE, GEMO Study Collaborators, kConFab Investigators, Consortium Investigators Modifiers

Publication type: Article

Publication status: Published

Journal: Cancer Epidemiology, Biomarkers & Prevention

Year: 2012

Volume: 21

Issue: 4

Pages: 645-657

Print publication date: 20/02/2012

ISSN (print): 1055-9965

ISSN (electronic): 1538-7755

Publisher: American Association for Cancer Research

URL: http://dx.doi.org/10.1158/1055-9965.EPI-11-0888

DOI: 10.1158/1055-9965.EPI-11-0888


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Funding

Funder referenceFunder name
Autonomous Government of Catalonia
Avon Foundation
Canadian Institutes of Health Research
Cancer Association of South Africa (CANSA)
Cancer Foundation of Western Australia
Center for Translational and Policy Research in Personalized Medicine (TRANSPERS)
DKFZ
Fondazione Italiana per la Ricerca sul Cancro
Helen Diller Family Comprehensive Cancer Center at UCSF
Icelandic Association "Walking for Breast Cancer Research"
Instituto Toscano Tumori grant
Komen Foundation for the Cure
Lymphoma Foundation
Ministero della Salute
National Breast Cancer Foundation
Neye Foundation
Norman and Carol Stone Cancer Research Initiative
Ohio State University Comprehensive Cancer Center
Queensland Cancer Fund
Sabin Family Research Initiative
Sigrid Juselius Foundation
Starr Cancer Consortium
Swing Fore the Cure
University Malaya
University of Kansas Cancer Center
Asociacion Espanola Contra el Cancer
Association "Le cancer du sein, parlons-en!"
Breast Cancer Family Registry (BCFR)
Breast Cancer Research Foundation
Cancer Care Ontario
Cancer Councils of New South Wales, Victoria, Tasmania
CARIF
Carlos III Health Institute
Catalan Health Institute
Centre of Molecular Medicine Cologne (CMMC)
Clinical Genetics Branch, DCEG
Community Oncology and Prevention Trials Program-COPTRG
CRUK
FCCC
Finnish Cancer Society
Fondazione IRCCS Istituto Nazionale Tumori
Fundacion Mutua Madrilena
Helsinki University Central Hospital
Jewish General Hospital
Kansas Bioscience Authority Eminent Scholar Program
Kate and Robert Niehaus Clinical Cancer Research Initiative
Landspitali University Hospital
Ligue National Contre le Cancer
Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR)
National Health and Medical Research Council (NHMRC)
NIHR
Polish Foundation of Science
Postgraduate School of Molecular Medicine, Warsaw Medical University
Royal Marsden NHS Foundation Trust
Spanish Health Research Fund
U.S. National Cancer Institute
Westat, Inc.
019511Canadian Breast Cancer Research Alliance
10-04-92110Russian Federation for Basic Research
10-04-92601Russian Federation for Basic Research
109076German Cancer Aid
11-04-00227Russian Federation for Basic Research
145684NHMRC
132473Academy of Finland
16.512.11.2237Federal Agency for Science and Innovations
2009SGR290
454508NHMRC
5U01CA113916
223175 (HEALTH-F2-2009-223175)European Community
91109024ZonMW
288704NHMRC
ACC2/R6.9"Ministero della Salute"
4017Associazione Italiana per la Ricerca sulCancro
BIO07/CA/006Basque Foundation for Health Innovation and Research (BIOEF)
CA-06-503U.S. National Cancer Institute, NIH under RFA
CA128978NIH
AICR-07-0454Association for International Cancer Research Grant
C12292/A11174Cancer Research UK (CR-UK)
C1287/A10118Cancer Research UK (CR-UK)
C1287/A10118CR-UK
C1287/A11990CR-UK
CA116201NCI
FIS PI08 1120Spanish Ministry of Science and Innovation
HHSN261200744000CCancer Genetics Network
KTIA-OTKACK-80745Hungarian Research Grant
LIG-19/2010Research Council of Lithuania
ISCIIIRETIC RD06/0020/1051
N02-CP-65504
NKI1998-1854Dutch Cancer Society
NKI2004-3088Dutch Cancer Society
P01 CA130818-02A1NIH/NCI
P30-CA051008Familial Cancer Registry at Georgetown University (NIH/NCI)
PI10/01422
PI10/31488
NKI2007-3756Dutch Cancer Society
NO2-CP-11019-50
RFA-CA-06-503National Cancer Institute, NIH
RFPS 2006-5-341353"Ministero della Salute"
SIOP-06-258-06-COUNAmerican Cancer Society
W81XWH-10-1-0341U.S. Department of Defence
RBLAO3-BETHMinistero dell'Universita' e Ricerca
U01CA69631

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