Journal
HUMAN MOLECULAR GENETICS
Volume 21, Issue 24, Pages 5373-5384Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/dds381
Keywords
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Funding
- Department of Defense [W81XWH-08-1-0383]
- Norris Foundation
- MEC (National Institutes of Health) [R01-CA63464, R37-CA54281]
- CARE (National Institute for Child Health and Development) [NO1-HD-3-3175]
- WCHS (U.S. Army Medical Research and Material Command (USAMRMC) [DAMD-17-01-0-0334]
- National Institutes of Health [R01-CA100598, CA 65725, CA87969, CA49449, CA67262, CA50385, 5UO1CA098233, CA109147, CA132839, CA54281, CA63464, CA120120]
- Breast Cancer Research Foundation
- SFBCS (National Institutes of Health) [R01-CA77305]
- SFBCS (United States Army Medical Research Program) [DAMD17-96-6071]
- NC-BCFR (National Institutes of Health) [U01-CA69417]
- CBCS (National Institutes of Health Specialized Program of Research Excellence in Breast Cancer [P50-CA58223]
- Center for Environmental Health and Susceptibility, National Institute of Environmental Health Sciences, National Institutes of Health [P30-ES10126]
- PLCO (Intramural Research Program, National Cancer Institute, National Institutes of Health)
- NBHS (National Institutes of Health) [R01-CA100374]
- WFBC (National Institutes of Health) [R01-CA73629]
- National Cancer Institute, National Institutes of Health [RFA CA-06-503]
- MCBCS (National Institutes of Health) [CA122340]
- Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]
- Breast Cancer Research Foundation (BCRF)
- MARIE (Deutsche Krebshilfe e.V.) [70-2892-BR I]
- Hamburg Cancer Society
- German Cancer Research Center (DKFZ)
- Federal Ministry of Education and Research (BMBF) Germany [01KH0402]
- GENICA (Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]
- Robert Bosch Foundation Stuttgart, Germany
- MCCS (Australian NHMRC) [209057, 251553, 504711]
- SBCS [Breast Cancer Campaign) [2004Nov49]
- Yorkshire Cancer Research
- DFCI (DFCI Breast Cancer SPORE NIH) [P50 CA089393]
- POSH (Cancer Research UK)
- DEMOKRITOS [Hellenic Cooperative Oncology Group] [HR R_BG/04]
- Greek General Secretary for Research and Technology (GSRT) Program
- European Union
- BBCC (Dr Mildred Scheel Stiftung of the Deutsche Krebshilfe e.V.)
- BBCS (Cancer Research UK)
- Breakthrough Breast Cancer
- NHS
- National Cancer Research Network (NCRN)
- LMBC (European Union) [LSHC-CT-2003-503297]
- Stichting tegen Kanker [232-2008]
- OBCS (Finnish Cancer Foundation)
- Sigrid Juselius Foundation
- University of Finland
- Oulu University Hospital
- HEBCS (Helsinki University Central Hospital Research Fund)
- Academy of Finland [132473]
- Finnish Cancer Society
- Nordic Cancer Union
- FCCC [U01CA69631, 5U01CA113916]
- University of Kansas Cancer Center
- Kansas Bioscience Authority Eminent Scholar Program
- RPCI (RPCI DataBank and BioRepository (DBBR)
- Cancer Center Support Grant Shared Resource [P30 CA016056-32]
- SKKDKFZS (Deutsches Krebsforschungszentrum)
- BIGGS (National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre
- Guy's & St. Thomas' NHS Foundation Trust
- King's College London and King's College Hospital NHS Foundation Trust
- ABCTB (National Health and Medical Research Council of Australia)
- Cancer Institute NSW
- National Breast Cancer Foundation
- ABCS (Dutch Cancer Society [2009-4363]
- KARBAC (The Stockholm Cancer Society)
- US National Institutes of Health, National Cancer Institute [U01-CA98233, U01-CA98710, U01-CA98216, U01-CA98758]
- NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics (PLCO)
- National Heart, Lung, and Blood Institute [HL043851, HL080467]
- National Cancer Institute [CA 047988]
- Donald W. Reynolds Foundation
- Fondation Leducq
- Amgen
- Wellcome Trust
- Cancer Research UK
- CR-UK [C1287/A10118, C1287/A12014]
- European Community [223175 (HEALTH-F2-2009-223175)]
- European Union [BM0606]
- National Health and Medical Research Council of Australia
- New South Wales Cancer Council
- Victorian Health Promotion Foundation (Australia)
- Institut National de Cancer
- Netherlands Organisation for Scientific Research (NWO) as part of a ZonMw/VIDI [91756341]
- Deutsche Krebshilfe [107054]
- Dietmar-Hopp Foundation
- Helmholtz society
- e German Cancer Research Centre (DKFZ)
- German Cancer Aid [107352]
- Deutsche Krebshilfe e.V. [70-2892-BR I]
- German Cancer Research Center
- Agency for Science, Technology and Research of Singapore (A*STAR)
- US National Institute of Health (NIH)
- Susan G. Komen Breast Cancer Foundation
- Helsinki University Central Hospital Research Fund
- Nordic Center of Excellence in Disease Genetics
- MRC [G0700491] Funding Source: UKRI
- Cancer Research UK [15106, 11022, 10118] Funding Source: researchfish
- Medical Research Council [G0700491] Funding Source: researchfish
- National Breast Cancer Foundation [IF-12-05, PF-11-20] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10124] Funding Source: researchfish
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Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P 1 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR 1.16; P 1.1 10(8)) but showed a weaker association with overall breast cancer (OR 1.08, P 1.3 10(6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR 1.01, P 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR 1.12; P 1.1 10(9)), and with both ER-positive (OR 1.09; P 1.5 10(5)) and ER-negative (OR 1.16, P 2.5 10(7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.
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