期刊
HUMAN MOLECULAR GENETICS
卷 20, 期 16, 页码 3289-3303出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddr228
关键词
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资金
- European Community [223175, HEALTH-F2-2009-223175]
- CR-UK [C1287/A10118, C1287/A7497, C1287/A12014, C8197/A10865]
- European Union [BM0606, LSHC-CT-2003-503297]
- National Health and Medical Research Council of Australia [199600]
- New South Wales Cancer Council
- Victorian Health Promotion Foundation (Australia)
- National Cancer Institute, National Institutes of Health [RFA-CA-06-503, CA-06-503, CA-58860]
- Dutch Cancer Society [NKI 2001-2423, 2007-3839, DDHK 2004-3124]
- Dutch National Genomics Initiative
- University of Erlangen
- Dr Mildred Scheel Stiftung of the Deutsche Krebshilfe e.V
- Dietmar-Hopp Foundation
- Helmholtz Society
- Chief Physician Johan Boserup and Lise Boserup Fund
- Danish Medical Research Council
- Copenhagen University Hospital, Herlev Hospital
- Red Tematica de Investigacion Cooperativa en Cancer
- Asociacion Espanola Contra Cancer
- Fondo de Investigacion Sanitario [PI081120, PI081583]
- Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]
- Deutsche Krebshilfe e.V [70492, 70-2892-BR I]
- Hannover Medical School
- Helsinki University Central Hospital
- Academy of Finland [110663]
- Finnish Cancer Society
- Sigrid Juselius Foundation
- Swedish Cancer Society
- Gustav V Jubilee Foundation
- Bert von Kantzow Foundation
- Kuopio University
- University of Kuopio
- EVO research funding of Vaasa Hospital District
- National Breast Cancer Foundation
- National Health and Medical Research Council (NHMRC) [145684, 288704, 454508, 209057, 251533, 396414, 504711, 504715]
- 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
- US Army Medical Research and Material Command [DAMD17-01-1-0729]
- Cancer Council Tasmania and Cancer Foundation of Western Australia
- Stichting tegen Kanker [232-2008]
- Hamburg Cancer Society
- German Cancer Research Center
- German Federal Ministry of Education and Research [01KH0402]
- National Institutes of Health [R01 CA122340, R01-CA63464, R37-CA54281]
- NCI Specialized Program of Research Excellence (SPORE) in breast cancer [P50 CA116201]
- Cancer Council Victoria
- Norwegian Research council [155218/V40, 175240/S10, 181600/V11]
- Swizz Bridge Award
- Cancer Care Ontario [U01 CA69467]
- Northern California Cancer Center [U01 CA69417]
- University of Melbourne [U01 CA69638]
- 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
- Breast Cancer Campaign
- Yorkshire Cancer Research
- Cancer Research UK [C1287/A10118, C490/A1102, C8197/A10123, C490/A10119, C490/A11020]
- NIHR Cambridge Biomedical Research Centre
- Cambridge Experimental Cancer Medicine Centre
- National Cancer Institute Thailand
- Institute of Biomedical Sciences, Academia Sinica, National Sciences Counciland Taiwan Biobank
- Lon V Smith Foundation [LVS-39420]
- [PBZ_KBN_122/P05/2004]
- Cancer Research UK [11022, 10118] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10124] Funding Source: researchfish
Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER+ than ER- tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 x 10(-18)), rs3803662 (16q12) (P = 3.7 x 10(-5)), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 x 10(-6) and P = 4.1 x 10(-4), respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P <= 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P <= 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.
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