Journal
PLOS GENETICS
Volume 10, Issue 4, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1004285
Keywords
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Categories
Funding
- Breast Cancer Campaign [2010NovPR61]
- National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust and King's College London
- Wellcome Trust Centre for Human Genetics (Wellcome Trust) [090532/Z/09/Z]
- Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program
- Ministry of Economic Development, Innovation and Export Trade of Quebec [PSR-SIIRI-701]
- European Community [223175, HEALTH-F2-2009-223175]
- United States National Cancer Institute, National Institutes of Health (NIH) [RFA-CA-06-503]
- Cancer Care Ontario [U01 CA69467]
- Northern California Cancer Center [U01 CA69417]
- University of Melbourne [U01 CA69638]
- National Health and Medical Research Council of Australia
- New South Wales Cancer Council
- Victorian Health Promotion Foundation (Australia)
- Victorian Breast Cancer Research Consortium
- Dutch Cancer Society [NKI 2007-3839, 2009-4363, RUL 1997-1505, DDHK 2004-3124, DDHK 2009-4318]
- ELAN-Fond of the University Hospital of Erlangen
- Cancer Research UK
- Breakthrough Breast Cancer
- NHS
- National Cancer Research Network (NCRN)
- CR-UK [C1287/A10118, C1287/A12014]
- European Union COST programme [BM0606]
- Oxford Biomedical Research Centre
- Dietmar-Hopp Foundation
- Helmholtz Society
- German Cancer Research Center (DKFZ)
- Fondation de France
- Institut National du Cancer (INCa)
- Ligue Nationale contre le Cancer
- Ligue contre le Cancer Grand Ouest
- Agence Nationale de Securite Sanitaire (ANSES)
- Agence Nationale de la Recherche (ANR)
- Lise Boserup Fund
- Danish Medical Research Council
- Herlev Hospital
- Genome Spain Foundation
- Red Tematica de Investigacion Cooperativa en Cancer
- Asociacion Espanola Contra el Cancer
- Fondo de Investigacion Sanitario [PI11/00923, PI081120]
- charity Against Breast Cancer [1121258]
- Baden Wurttemberg Ministry of Science, Research and Arts
- German Cancer Aid (Deutsche Krebshilfe)
- Deutsche Krebshilfe [107 352]
- Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]
- Robert Bosch Foundation
- Stuttgart
- Deutsches Krebsforschungszentrum (DKFZ), Heidelberg
- Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum
- Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH
- Johanniter Krankenhaus, Bonn, Germany
- Helsinki University Central Hospital Research Fund
- Academy of Finland [132473]
- Finnish Cancer Society
- Nordic Cancer Union
- Sigrid Juselius Foundation
- Friends of Hannover Medical School
- Rudolf Bartling Foundation
- Stockholm County Council
- Karolinska Institutet
- Swedish Cancer Society
- Bert von Kantzow foundation
- Kuopio University Hospital grants
- Cancer Fund of North Savo
- Finnish Cancer Organizations
- Academy of Finland
- University of Eastern Finland
- National Breast Cancer Foundation
- NHMRC
- Queensland Cancer Fund
- Cancer Councils of New South Wales, Victoria, Tasmania and South Australia
- Cancer Foundation of Western Australia
- NHMRC [145684, 288704, 454508, 199600]
- United States Army Medical Research and Materiel Command [DAMD17-01-1-0729]
- Cancer Council of Tasmania
- Stichting tegen Kanker [232-2008, 196-2010]
- FWO
- Deutsche Krebshilfe e.V. [70-2892-BR I]
- Hamburg Cancer Society
- German Cancer Research Center
- Italian Association for Cancer Research (AIRC)
- Fondazione IRCCS Istituto Nazionale Tumori [561000]
- NIH [CA128978, CA63464, CA54281, CA098758, CA132839]
- NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]
- Breast Cancer Research Foundation
- VicHealth and Cancer Council Victoria
- Australian NHMRC [209057, 251553, 504711]
- MTLGEBCS: The Quebec Breast Cancer Foundation
- Norwegian Research council [FUGE-NFR 181600/V11]
- Finnish Cancer Foundation
- University of Oulu
- Oulu University Hospital
- Canadian Institutes of Health Research CIHR Team in Familial Risks of Breast Cancer program
- National Cancer Institute/NIH (USA) [UM1 CA164920]
- Biobanking and Biomolecular Resources Research Infrastructure [BBMRI-NL CP16]
- Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA
- Agency for Science, Technology and Research of Singapore (A*STAR)
- US National Institute of Health (NIH)
- Susan G. Komen Breast Cancer Foundation
- Yorkshire Cancer Research [S295, S299, S305PA]
- Cancer Research UK [C490/A10124]
- UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge
- DKFZ, Heidelberg, Germany
- Polish Foundation of Science
- Institute of Cancer Research (ICR)
- [KULPFV/10/016-SymBioSysII]
- Cancer Foundation Finland sr [110135] Funding Source: researchfish
- Cancer Research UK [16565, 16563, 16459, 16561] Funding Source: researchfish
- National Breast Cancer Foundation [IF-12-06] Funding Source: researchfish
- National Institute for Health Research [03/DHCS/03/G121/51] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10124] Funding Source: researchfish
Ask authors/readers for more resources
Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95% CI) for ILC = 1.13 (1.09-1.18), P = 6.0x10(-10); P-het for ILC vs IDC ER+ tumors = 1.8x10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.
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