Genetic predisposition to ductal carcinoma in situ of the breast

Journal article

Publication Details

Author(s): Petridis C, Brook MN, Shah V, Kohut K, Gorman P, Caneppele M, Levi D, Papouli E, Orr N, Cox A, Cross SS, Dos-Santos-Silva I, Peto J, Swerdlow A, Schoemaker MJ, Bolla MK, Wang Q, Dennis J, Michailidou K, Benitez J, Gonzalez-Neira A, Tessier DC, Vincent D, Li J, Figueroa J, Kristensen V, Borresen-Dale AL, Soucy P, Simard J, Milne RL, Giles GG, Margolin S, Lindblom A, Bruening T, Brauch H, Southey MC, Hopper JL, Doerk T, Bogdanova NV, Kabisch M, Hamann U, Schmutzler RK, Meindl A, Brenner H, Arndt V, Winqvist R, Pylkas K, Fasching P, Beckmann M, Lubinski J, Jakubowska A, Mulligan AM, Andrulis IL, Tollenaar RAEM, Devilee P, Le Marchand L, Haiman CA, Mannermaa A, Kosma VM, Radice P, Peterlongo P, Marme F, Burwinkel B, Van Deurzen CHM, Hollestelle A, Miller N, Kerin MJ, Lambrechts D, Floris G, Wesseling J, Flyger H, Bojesen SE, Yao S, Ambrosone CB, Chenevix-Trench G, Truong T, Guenel P, Rudolph A, Chang-Claude J, Nevanlinna H, Blomqvist C, Czene K, Brand JS, Olson JE, Couch FJ, Dunning AM, Hall P, Easton DF, Pharoah PDP, Pinder SE, Schmidt MK, Tomlinson I, Roylance R, Garcia-Closas M, Sawyer EJ
Journal: Breast Cancer Research
Publication year: 2016
Volume: 18
Journal issue: 1
ISSN: 1465-542X


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.

FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe

External institutions with authors

Antoni van Leeuwenhoek
Cancer Council Victoria
Deutsches Krebsforschungszentrum (DKFZ)
Erasmus University Medical Center
Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Helsingin yliopisto / University of Helsinki
Herlev Hospital
IFOM - FIRC Institute of Molecular Oncology
Istituto di ricovero e cura a carattere scientifico (IRCCS)
Karolinska Institute
King’s College London
Kuopio University Hospital / Pohjois-Savon sairaanhoitopiiri
Leiden University
London School of Hygiene and Tropical Medicine
Mayo Clinic
McGill University and Génome Québec Innovation Centre
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
National University of Ireland (NUI), Galway
Oslo universitetssykehus Rikshospitalet
Oulun Yliopisto / University of Oulo
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Queen Mary, University of London
Roswell Park Cancer Institute
Ruhr-Universität Bochum (RUB)
Ruprecht-Karls-Universität Heidelberg
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
Technische Universität München (TUM)
The Institute of Cancer Research (ICR)
The University of Melbourne
Universität Köln
Université Laval (UL)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of Cambridge
University of Hawaii (U.H.)
University of Oxford
University of Sheffield
University of Southern California (USC)
University of Toronto

How to cite

Petridis, C., Brook, M.N., Shah, V., Kohut, K., Gorman, P., Caneppele, M.,... Sawyer, E.J. (2016). Genetic predisposition to ductal carcinoma in situ of the breast. Breast Cancer Research, 18(1).

Petridis, Christos, et al. "Genetic predisposition to ductal carcinoma in situ of the breast." Breast Cancer Research 18.1 (2016).


Last updated on 2019-21-07 at 08:06