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Breast Cancer Res. 2016 Feb 17;18(1):22. doi: 10.1186/s13058-016-0675-7.

Genetic predisposition to ductal carcinoma in situ of the breast.

Author information

1
Research Oncology, Guy's Hospital, King's College London, London, UK. christos.petridis@kcl.ac.uk.
2
Medical and Molecular Genetics, Guy's Hospital, King's College London, London, UK. christos.petridis@kcl.ac.uk.
3
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. Mark.Brook@icr.ac.uk.
4
Research Oncology, Guy's Hospital, King's College London, London, UK. vandna.shah@kcl.ac.uk.
5
Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK. kohut.kelly@gmail.com.
6
Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK. patricia.carlyle@me.com.
7
Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK. michele.caneppele@novartis.com.
8
Research Oncology, Guy's Hospital, King's College London, London, UK. dinalevi@gmail.com.
9
Biomedical Research Centre, King's College London, Guy's Hospital, London, UK. efterpi@cegx.co.uk.
10
The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK. Nicholas.Orr@icr.ac.uk.
11
Sheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield, UK. a.cox@shef.ac.uk.
12
Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK. s.s.cross@sheffield.ac.uk.
13
Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. isabel.silva@lshtm.ac.uk.
14
Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. Julian.Peto@lshtm.ac.uk.
15
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. Anthony.Swerdlow@icr.ac.uk.
16
Division of Breast Cancer Research, The Institute of Cancer Research, London, UK. Anthony.Swerdlow@icr.ac.uk.
17
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. minouk.schoemaker@icr.ac.uk.
18
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. mkh39@medschl.cam.ac.uk.
19
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. qw232@medschl.cam.ac.uk.
20
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. jgd29@cam.ac.uk.
21
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. km533@medschl.cam.ac.uk.
22
Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain. jbenitez@cnio.es.
23
Centro de Investigación en Red de Enfermedades Raras, Valencia, Spain. jbenitez@cnio.es.
24
Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain. agonzalez@cnio.es.
25
Centre d'innovation Génome Québec et Université McGill, Montréal, Canada. dtessier@genomequebec.com.
26
Centre d'innovation Génome Québec et Université McGill, Montréal, Canada. daniel.vincent@mail.mcgill.ca.
27
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. jingmei@gmail.com.
28
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. figueroaj@mail.nih.gov.
29
Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway. v.n.kristensen@medisin.uio.no.
30
K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. v.n.kristensen@medisin.uio.no.
31
Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway. v.n.kristensen@medisin.uio.no.
32
Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway. a.l.borresen-dale@medisin.uio.no.
33
K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. a.l.borresen-dale@medisin.uio.no.
34
Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada. penny.soucy@crchudequebec.ulaval.ca.
35
Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada. jacques.simard@crchul.ulaval.ca.
36
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. Roger.Milne@cancervic.org.au.
37
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, VIC, Australia. Roger.Milne@cancervic.org.au.
38
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. Graham.Giles@cancervic.org.au.
39
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, VIC, Australia. Graham.Giles@cancervic.org.au.
40
Department of Oncology - Pathology, Karolinska Institutet, Stockholm, Sweden. Sara.Margolin@karolinska.se.
41
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. Annika.Lindblom@ki.se.
42
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum, Bochum, Germany. bruening@ipa-dguv.de.
43
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany. hiltrud.brauch@ikp-stuttgart.de.
44
University of Tübingen, Tübingen, Germany. hiltrud.brauch@ikp-stuttgart.de.
45
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. hiltrud.brauch@ikp-stuttgart.de.
46
Department of Pathology, The University of Melbourne, Melbourne, Australia. msouthey@unimelb.edu.au.
47
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, VIC, Australia. j.hopper@unimelb.edu.au.
48
Gynaecology Research Unit, Hannover Medical School, Hannover, Germany. doerk.thilo@mh-hannover.de.
49
Department of Radiation Oncology, Hannover Medical School, Hannover, Germany. bogdanova.natalia@mh-hannover.de.
50
Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany. m.kabisch@dkfz.de.
51
Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany. u.hamann@dkfz-heidelberg.de.
52
Center for Familial Breast and Ovarian Cancer, Medical Faculty, University of Cologne and University Hospital Cologne, Cologne, Germany. rita.schmutzler@uk-koeln.de.
53
Center for Integrated Oncology (CIO), Medical Faculty, University of Cologne and University Hospital Cologne, Cologne, Germany. rita.schmutzler@uk-koeln.de.
54
Center for Molecular Medicine Cologne (CMMC), Medical Faculty, University of Cologne and University Hospital Cologne, Cologne, Germany. rita.schmutzler@uk-koeln.de.
55
Division of Gynaecology and Obstetrics, Technische Universität München, Munich, Germany. alfons.meindl@lrz.tu-muenchen.de.
56
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. h.brenner@dkfz.de.
57
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. h.brenner@dkfz.de.
58
Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. h.brenner@dkfz.de.
59
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. v.arndt@dkfz.de.
60
Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland. robert.winqvist@oulu.fi.
61
Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre NordLab, Oulu, Finland. robert.winqvist@oulu.fi.
62
Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland. katri.pylkas@oulu.fi.
63
Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre NordLab, Oulu, Finland. katri.pylkas@oulu.fi.
64
Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany. peter.fasching@uk-erlangen.de.
65
David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, CA, USA. peter.fasching@uk-erlangen.de.
66
Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany. Fk-direktion@uk-erlangen.de.
67
Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. lubinski@pum.edu.pl.
68
Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. aniaj@pum.edu.pl.
69
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. AnnaMarie.Mulligan@uhn.ca.
70
Laboratory Medicine Program, University Health Network, Toronto, Canada. AnnaMarie.Mulligan@uhn.ca.
71
Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada. andrulis@lunenfeld.ca.
72
Department of Molecular Genetics, University of Toronto, Toronto, Canada. andrulis@lunenfeld.ca.
73
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. r.a.e.m.tollenaar@lumc.nl.
74
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. p.devilee@lumc.nl.
75
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. p.devilee@lumc.nl.
76
University of Hawaii Cancer Center, Honolulu, HI, USA. loic@crch.hawaii.edu.
77
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Christopher.Haiman@med.usc.edu.
78
Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland. arto.mannermaa@uef.fi.
79
Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland. arto.mannermaa@uef.fi.
80
Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland. arto.mannermaa@uef.fi.
81
Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland. veli-matti.kosma@uef.fi.
82
Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland. veli-matti.kosma@uef.fi.
83
Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland. veli-matti.kosma@uef.fi.
84
Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT), Milan, Italy. paolo.radice@istitutotumori.mi.it.
85
IFOM, Fondazione Istituto FIRC (Italian Foundation of Cancer Research) di Oncologia Molecolare, Milan, Italy. paolo.peterlongo@ifom.eu.
86
National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany. frederikmarme@gmail.com.
87
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany. frederikmarme@gmail.com.
88
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany. Barbara.Burwinkel@med.uni-heidelberg.de.
89
Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. Barbara.Burwinkel@med.uni-heidelberg.de.
90
Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands. c.h.m.vandeurzen@erasmusmc.nl.
91
Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. a.hollestelle@erasmusmc.nl.
92
School of Medicine, National University of Ireland, Galway, Ireland. nicola.miller@nuigalway.ie.
93
School of Medicine, National University of Ireland, Galway, Ireland. michael.kerin@nuigalway.ie.
94
Vesalius Research Center, VIB, Leuven, Belgium. Diether.Lambrechts@med.kuleuven.be.
95
Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium. Diether.Lambrechts@med.kuleuven.be.
96
University Hospital Gashuisberg, Leuven, Belgium. Giuseppe.Floris@uzleuven.be.
97
Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands. j.wesseling@nki.nl.
98
Department of Breast Surgery, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark. henrik.flyger@regionh.dk.
99
Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark. stig.egil.bojesen@regionh.dk.
100
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark. stig.egil.bojesen@regionh.dk.
101
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. stig.egil.bojesen@regionh.dk.
102
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA. song.yao@roswellpark.org.
103
Roswell Park Cancer Institute, Buffalo, NY, USA. Christine.ambrosone@roswellpark.org.
104
Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia. Georgia.Trench@qimrberghofer.edu.au.
105
Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France. therese.truong@inserm.fr.
106
University Paris-Sud, Villejuif, France. therese.truong@inserm.fr.
107
Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France. pascal.guenel@inserm.fr.
108
University Paris-Sud, Villejuif, France. pascal.guenel@inserm.fr.
109
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. a.rudolph@dkfz.de.
110
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. j.chang-claude@dkfz-heidelberg.de.
111
Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. Heli.Nevanlinna@hus.fi.
112
Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. carl.blomqvist@helsinki.fi.
113
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. kamila.czene@ki.se.
114
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. judith.brand@ki.se.
115
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. olsonj@mayo.edu.
116
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. couch.fergus@mayo.edu.
117
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK. amd24@medschl.cam.ac.uk.
118
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Per.Hall@ki.se.
119
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. dfe20@medschl.cam.ac.uk.
120
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK. dfe20@medschl.cam.ac.uk.
121
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. pp10001@medschl.cam.ac.uk.
122
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK. pp10001@medschl.cam.ac.uk.
123
Research Oncology, Guy's Hospital, King's College London, London, UK. sarah.pinder@kcl.ac.uk.
124
Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands. mk.schmidt@nki.nl.
125
Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK. iant@well.ox.ac.uk.
126
Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK. r.roylance@qmul.ac.uk.
127
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. montserrat.garcia-closas@nih.gov.
128
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. montserrat.garcia-closas@nih.gov.
129
Research Oncology, Guy's Hospital, King's College London, London, UK. elinor.sawyer@kcl.ac.uk.

Abstract

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.

PMID:
26884359
PMCID:
PMC4756509
DOI:
10.1186/s13058-016-0675-7
[Indexed for MEDLINE]
Free PMC Article

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