Genetic predisposition to in situ and invasive lobular carcinoma of the breast

Journal article


Publication Details

Author(s): Sawyer E, Roylance R, Petridis C, Brook MN, Nowinski S, Papouli E, Fletcher O, Pinder S, Hanby A, Kohut K, Gorman P, Caneppele M, Peto J, Silva IDS, Johnson N, Swann R, Dwek M, Perkins KA, Gillett C, Houlston R, Ross G, De Ieso P, Southey MC, Hopper JL, Provenzano E, Apicella C, Wesseling J, Cornelissen S, Keeman R, Fasching PA, Jud S, Ekici AB, Beckmann M, Kerin MJ, Marme F, Schneeweiss A, Sohn C, Burwinkel B, Guenel P, Truong T, Laurent-Puig P, Kerbrat P, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Milne RL, Perez JIA, Menendez P, Benitez J, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Meindl A, Lichtner P, Schmutzler RK, Lochmann M, Brauch H, Fischer HP, Ko YD, Nevanlinna H, Muranen TA, Aittomaki K, Blomqvist C, Bogdanova NV, Dork T, Lindblom A, Margolin S, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Chenevix-Trench G, Lambrechts D, Weltens C, Van Limbergen E, Hatse S, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Radice P, Peterlongo P, Bonanni B, Volorio S, Giles GG, Severi G, Baglietto L, Mclean CA, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Simard J, Goldberg MS, Labreche F, Dumont M, Kristensen V, Winqvist R, Pylkas K, Jukkola-Vuorinen A, Kauppila S, Andrulis IL, Knight JA, Glendon G, Mulligan AM, Devillee P, Tollenaar RAEM, Seynaeve CM, Kriege M, Figueroa J, Chanock SJ, Sherman ME, Hooning MJ, Hollestelle A, Van Den Ouweland AMW, Van Deurzen CHM, Li J, Czene K, Humphreys K, Cox A, Cross SS, Reed MWR, Shah M, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Swerdlow A, Ashworth A, Orr N, Schoemaker M, Couch FJ, Hallberg E, Gonzalez-Neira A, Pita G, Alonso MR, Tessier DC, Vincent D, Bacot F, Bolla MK, Wang Q, Dennis J, Michailidou K, Dunning AM, Hall P, Easton D, Pharoah P, Schmidt MK, Tomlinson I, Garcia-Closas M
Journal: Plos Genetics
Publication year: 2014
Volume: 10
Journal issue: 4
Pages range: e1004285
ISSN: 1553-7390
eISSN: 1553-7404


Abstract


Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.



FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe
Jud, Sebastian Dr.
Frauenklinik


External institutions with authors

Addenbrooke's Hospital
Antoni van Leeuwenhoek
Cancer Council Victoria
Centre Eugène Marquis
Centre hospitalier universitaire de Québec
Copenhagen University Hospital
Deutsches Krebsforschungszentrum (DKFZ)
Erasmus University Medical Center
Erasmus University Medical Center (MC)
Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam
European Institute of Oncology / Istituto Europeo di Oncologia (IEO)
Evangelische Kliniken Bonn gGmbH
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Fondazione IRCCS: Istituto Nazionale dei Tumori
Genome Institute of Singapore
Hannover Medical School / Medizinische Hochschule Hannover (MHH)
Helsingin yliopisto / University of Helsinki
Hospital Monte Naranco
IFOM - FIRC Institute of Molecular Oncology
Karolinska Institute
King’s College London
Krebsregister Saarland / Saarland Cancer Registry
Leiden University
London School of Hygiene and Tropical Medicine
Mayo Clinic
McGill University
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
National University of Ireland (NUI), Galway
Oslo University Hospital / Oslo Universitetssykehus
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
Research Center in Epidemiology and Population Health / Centre de recherche en Epidémiologie et Santé des Populations (CESP)
Rheinische Friedrich-Wilhelms-Universität Bonn
Robert-Bosch-Krankenhaus
Ruprecht-Karls-Universität Heidelberg
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
St James's University Hospital
Technische Universität München (TUM)
The Alfred Hospital
The Royal Marsden NHS Foundation Trust
The University of Melbourne
Universitätsklinikum Köln
Université de Montréal
University College London (UCL)
University Health Network (UHN)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of Cambridge
University of Copenhagen
University of Eastern Finland
University of Hawaii (U.H.)
University of Oxford
University of Paris 4 - Paris-Sorbonne / Université paris IV Paris-Sorbonne
University of Sheffield
University of Southern California (USC)
University of Westminster


How to cite

APA:
Sawyer, E., Roylance, R., Petridis, C., Brook, M.N., Nowinski, S., Papouli, E.,... Garcia-Closas, M. (2014). Genetic predisposition to in situ and invasive lobular carcinoma of the breast. Plos Genetics, 10(4), e1004285. https://dx.doi.org/10.1371/journal.pgen.1004285

MLA:
Sawyer, Elinor, et al. "Genetic predisposition to in situ and invasive lobular carcinoma of the breast." Plos Genetics 10.4 (2014): e1004285.

BibTeX: 

Last updated on 2018-10-10 at 08:22