Article
Genetic predisposition to ductal carcinoma in situ of the breast
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- (1) King's College London, grid.13097.3c
- (2) Institute of Cancer Research, grid.18886.3f
- (3) Queen Mary University of London, grid.4868.2
- (4) University of Sheffield, grid.11835.3e
- (5) London School of Hygiene & Tropical Medicine, grid.8991.9
- (6) University of Cambridge, grid.5335.0
- (7) Centro de Investigación en Red de Enfermedades Raras, Valencia, Spain
- (8) Spanish National Cancer Research Centre, grid.7719.8
- (9) McGill University and Génome Québec Innovation Centre, grid.411640.6
- (10) Karolinska Institute, grid.4714.6
- (11) National Cancer Institute, grid.48336.3a
- (12) Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway
- (13) K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- (14) Oslo University Hospital, grid.55325.34
- (15) Laval University, grid.23856.3a
- (16) Cancer Council Victoria, grid.3263.4
- (17) University of Melbourne, grid.1008.9
- (18) Ruhr University Bochum, grid.5570.7
- (19) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
- (20) University of Tübingen, grid.10392.39
- (21) German Cancer Research Center, grid.7497.d
- (22) Hannover Medical School, grid.10423.34
- (23) University Hospital Cologne, grid.411097.a
- (24) Technical University of Munich, grid.6936.a
- (25) Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre NordLab, Oulu, Finland
- (26) University of Oulu, grid.10858.34
- (27) University of California, Los Angeles, grid.19006.3e
- (28) Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- (29) Pomeranian Medical University, grid.107950.a
- (30) University Health Network, grid.231844.8
- (31) University of Toronto, grid.17063.33
- (32) Lunenfeld-Tanenbaum Research Institute, grid.250674.2
- (33) Leiden University Medical Center, grid.10419.3d
- (34) University of Hawaii at Manoa, grid.410445.0
- (35) University of Southern California, grid.42505.36
- (36) Kuopio University Hospital, grid.410705.7
- (37) University of Eastern Finland, grid.9668.1
- (38) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
- (39) IFOM, Fondazione Istituto FIRC (Italian Foundation of Cancer Research) di Oncologia Molecolare, Milan, Italy
- (40) National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany
- (41) Heidelberg University, grid.7700.0
- (42) Erasmus University Medical Center, grid.5645.2
- (43) National University of Ireland, Galway, grid.6142.1
- (44) Flanders Institute for Biotechnology, grid.11486.3a
- (45) KU Leuven, grid.5596.f
- (46) Universitair Ziekenhuis Leuven, grid.410569.f
- (47) Antoni van Leeuwenhoek Hospital, grid.430814.a
- (48) Herlev Hospital, grid.411900.d, Capital Region
- (49) University of Copenhagen, grid.5254.6, KU
- (50) Roswell Park Cancer Institute, grid.240614.5
- (51) QIMR Berghofer Medical Research Institute, grid.1049.c
- (52) French Institute of Health and Medical Research, grid.7429.8
- (53) University of Paris-Sud, grid.5842.b
- (54) Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
- (55) Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
- (56) Mayo Clinic, grid.66875.3a
- (57) University of Oxford, grid.4991.5
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Description
BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. METHODS: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. RESULTS: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10(-8). CONCLUSION: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.
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