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

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 P, 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 (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Book Volume: 10

Pages Range: e1004285

Journal Issue: 4

DOI: 10.1371/journal.pgen.1004285

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.

Authors with CRIS profile

Involved external institutions

King’s College London United Kingdom (GB) Queen Mary, University of London United Kingdom (GB) St James's University Hospital United Kingdom (GB) London School of Hygiene and Tropical Medicine United Kingdom (GB) University of Westminster United Kingdom (GB) Royal Marsden Hospital / The Royal Marsden NHS Foundation Trust United Kingdom (GB) The University of Melbourne Australia (AU) University of Southern California (USC) United States (USA) (US) University College London (UCL) United Kingdom (GB) Addenbrooke's Hospital United Kingdom (GB) Antoni van Leeuwenhoek Netherlands (NL) Mount Sinai Hospital (MSH) Canada (CA) University Health Network (UHN) Canada (CA) Leiden University Netherlands (NL) Erasmus University Medical Center (MC) Netherlands (NL) National Cancer Institute (NCI) United States (USA) (US) Ruprecht-Karls-Universität Heidelberg Germany (DE) Research Center in Epidemiology and Population Health / Centre de recherche en Epidémiologie et Santé des Populations (CESP) France (FR) National University of Ireland (NUI), Galway Ireland (IE) Universitätsklinikum Köln Germany (DE) Centre Eugène Marquis France (FR) University of Copenhagen Denmark (DK) Copenhagen University Hospital Denmark (DK) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Hospital Monte Naranco Spain (ES) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Krebsregister Saarland / Saarland Cancer Registry Germany (DE) Technische Universität München (TUM) Germany (DE) Robert-Bosch-Krankenhaus Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Helsingin yliopisto / University of Helsinki Finland (FI) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Karolinska Institute Sweden (SE) University of Eastern Finland Finland (FI) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) IFOM - FIRC Institute of Molecular Oncology Italy (IT) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) Italy (IT) Cancer Council Victoria Australia (AU) The Alfred Hospital Australia (AU) University of Hawaii (U.H.) United States (USA) (US) Centre hospitalier universitaire de Québec Canada (CA) McGill University Canada (CA) Université de Montréal Canada (CA) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Oulun Yliopisto / University of Oulo Finland (FI) Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam Netherlands (NL) Evangelische Kliniken Bonn gGmbH Germany (DE) University of Paris 4 - Paris-Sorbonne / Université paris IV Paris-Sorbonne France (FR) Genome Institute of Singapore Singapore (SG) University of Sheffield United Kingdom (GB) University of Cambridge United Kingdom (GB) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Mayo Clinic United States (USA) (US) University of Oxford United Kingdom (GB)

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://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.

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