期刊
HUMAN MOLECULAR GENETICS
卷 23, 期 22, 页码 6096-6111出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddu311
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资金
- Cancer Research UK [C1287/A10118, C1287/A12014, C1287/A10710, C490/A10124]
- European Community [223175, HEALTH-F2-2009-223175]
- European Union COST programme [BM0606]
- European Union [HEALTH-F2-2009-223175]
- Canadian Institutes of Health Research
- Ministry of Economic Development, Innovation and Export Trade of Quebec [PSR-SIIRI-701]
- National Cancer Institute (USA) [UM1 CA164920]
- National Health and Medical Research Council of Australia
- New South Wales Cancer Council
- Victorian Health Promotion Foundation (Australia)
- Victorian Breast Cancer Research Consortium
- National Health and Medical Research Council (NHMRC)
- Dutch Cancer Society [NKI2007-3839, NKI2009-4363, RUL 1997-1505, DDHK 2004-3124, DDHK 2009-4318]
- Breast Cancer Research Trust, UK
- University Hospital of Erlangen
- Cancer Research UK
- Breakthrough Breast Cancer
- NHS
- National Cancer Research Network (NCRN)
- NIHR Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust
- King's College London, UK
- Wellcome Trust [090532/Z/09/Z]
- Oxford Biomedical Research Centre
- Dietmar-Hopp Foundation
- Helmholtz Society
- German Cancer Research Center (DKFZ)
- Fondation de France
- French National Institute of Cancer (INCa)
- The National League against Cancer
- National Agency for Environmental and Occupational Health and Food Safety (ANSES)
- National Agency for Research (ANR)
- Association for Research against Cancer (ARC)
- Chief Physician Johan Boserup and 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]
- Instituto de Salud Carlos III
- Michael Manzella Foundation (MMF)
- California Breast Cancer Act
- California Breast Cancer Research Fund [97-10500]
- National Institutes of Health [R01 CA77398]
- Lon V Smith Foundation [LVS39420]
- Baden Wurttemberg Ministry of Science, Research and Arts
- German Cancer Aid (Deutsche Krebshilfe)
- Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114, 01KH0402]
- Robert Bosch Foundation, Stuttgart
- Deutsches Krebsforschungszentrum (DKFZ), Heidelberg
- Institute for Prevention and Occupational Medicine of the German Social Accident Insurance
- Institute of the Ruhr University Bochum (IPA)
- 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
- The Nordic Cancer Union
- Sigrid Juselius Foundation
- Ministry of Education, Science, Sports, Culture and Technology of Japan
- Ministry Health, Labour and Welfare of Japan
- Takeda Science Foundation
- National Cancer Center Research and Development Fund
- German Academic Exchange Program
- Friends of Hannover Medical School
- Stockholm County Council
- Karolinska Institutet
- Stockholm Cancer Foundation
- Swedish Cancer Society
- Kuopio University Hospital
- Cancer Fund of North Savo
- Finnish Cancer Organizations
- University of Eastern Finland
- National Breast Cancer Foundation
- NHMRC
- Queensland Cancer Fund
- Cancer Council of New South Wales
- Cancer Council of Victoria
- Cancer Council of Tasmania
- Cancer Council of South Australia
- Cancer Foundation of Western Australia
- NHMRC [145684, 288704, 454508, 199600]
- United States Army Medical Research and Materiel Command [DAMD17-01-1-0729]
- California Breast Cancer Research Program [1RB-0287, 3PB-0102, 5PB-0018, 10PB-0098]
- California Department of Health
- National Cancer Institute's Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program [N01CN25403]
- Stichting tegen Kanker [232-2008, 196-2010]
- Deutsche Krebshilfe e.V. [70-2892-BR I]
- Hamburg Cancer Society
- Italian Association for Cancer Research (AIRC)
- Fondazione IRCCS Istituto Nazionale Tumori
- NIH [CA122340, CA128978, CA63464, CA54281, CA098758, CA132839, R01CA100374, R01CA64277, R01CA148667, R37CA70867, R01 CA092447]
- Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]
- Breast Cancer Research Foundation
- VicHealth
- Cancer Council Victoria
- Australian NHMRC [209057, 251553, 504711]
- Quebec Breast Cancer Foundation
- Canadian Institutes of Health Research [CRN-87521]
- Ministry of Economic Development, Innovation and Export Trade [PSR-SIIRI-701]
- Malaysian Ministry of Science, Technology and Innovation (MOSTI)
- Malaysian Ministry of Higher Education [UM.C/HlR/MOHE/06]
- Cancer Research Initiatives Foundation (CARIF)
- Biomedical Research Council, Singapore [BMRC08/1/35/19]
- National medical Research Council, Singapore [NMRC/CG/SERI/2010]
- Norwegian Research council [155218/V40, 175240/S10, FUGE-NFR 181600/V11]
- Norwegian Research council (Swizz Bridge Award)
- Finnish Cancer Foundation
- University of Oulu
- Oulu University Hospital
- Biobanking and Biomolecular Resources Research Infrastructure [BBMRI-NL CP16]
- National Cancer Institute, Department of Health and Human Services, USA
- Marit and Hans Rausings Initiative Against Breast Cancer
- Cancer Risk Prediction Center (CRisP)
- Linnaeus Centre - Swedish Research Council [70867902]
- Agency for Science, Technology and Research of Singapore (A*STAR)
- US National Institute of Health (NIH)
- Susan G. Komen Breast Cancer Foundation
- Swedish Cancer Society [5128-B07-01PAF]
- Yorkshire Cancer Research [S305PA, S299, S295]
- National Program of Cancer Registries, Centers for Disease Control and Prevention (CDC)
- UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge
- BRL (Basic Research Laboratory) program through the National Research Foundation of Korea - Ministry of Education, Science and Technology [2012-0000347]
- National Medical Research Council Start-up Grant
- National Medical Research Council Centre Grant [NMRC/CG/NCIS /2010]
- Biomedical Research Council [05/1/21/19/425]
- DKFZ
- Polish Foundation of Science
- Komen Foundation for the Cure
- Ohio State University Comprehensive Cancer Center
- Stefanie Spielman Fund for Breast Cancer Research
- European Union (European Social Fund - ESF)
- Greek National Funds through the Operational Program 'Education and Lifelong Learning' of the National Strategic Reference Framework (NSRF)-Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA
- Institute of Biomedical Sciences
- Academia Sinica
- National Science Council, Taiwan
- Institute of Cancer Research (ICR)
- Wellcome Trust
- [P30 CA68485]
- [PBZ_KBN_122/P05/2004]
- Cancer Foundation Finland sr [130168] Funding Source: researchfish
- Cancer Research UK [11022, 16563, 10118, 16565, 16561] Funding Source: researchfish
- Cancer Research UK
- The Francis Crick Institute [10124] 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
Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 x 10 26], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 x 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 x 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 x 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 x 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.
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