| Literature DB >> 24743323 |
Elinor Sawyer1, Rebecca Roylance2, Christos Petridis1, Mark N Brook3, Salpie Nowinski1, Efterpi Papouli4, Olivia Fletcher5, Sarah Pinder1, Andrew Hanby6, Kelly Kohut2, Patricia Gorman2, Michele Caneppele2, Julian Peto7, Isabel Dos Santos Silva7, Nichola Johnson5, Ruth Swann8, Miriam Dwek8, Katherine-Anne Perkins8, Cheryl Gillett1, Richard Houlston3, Gillian Ross9, Paolo De Ieso9, Melissa C Southey10, John L Hopper11, Elena Provenzano12, Carmel Apicella11, Jelle Wesseling13, Sten Cornelissen13, Renske Keeman13, Peter A Fasching14, Sebastian M Jud15, Arif B Ekici16, Matthias W Beckmann15, Michael J Kerin17, Federick Marme18, Andreas Schneeweiss18, Christof Sohn19, Barbara Burwinkel20, Pascal Guénel21, Therese Truong21, Pierre Laurent-Puig22, Pierre Kerbrat23, Stig E Bojesen24, Børge G Nordestgaard24, Sune F Nielsen24, Henrik Flyger25, Roger L Milne26, Jose Ignacio Arias Perez27, Primitiva Menéndez28, Javier Benitez29, Hermann Brenner30, Aida Karina Dieffenbach30, Volker Arndt30, Christa Stegmaier31, Alfons Meindl32, Peter Lichtner33, Rita K Schmutzler34, Magdalena Lochmann32, Hiltrud Brauch35, Hans-Peter Fischer36, Yon-Dschun Ko37, Heli Nevanlinna38, Taru A Muranen38, Kristiina Aittomäki39, Carl Blomqvist40, Natalia V Bogdanova41, Thilo Dörk42, Annika Lindblom43, Sara Margolin44, Arto Mannermaa45, Vesa Kataja45, Veli-Matti Kosma45, Jaana M Hartikainen45, Georgia Chenevix-Trench46, Diether Lambrechts47, Caroline Weltens48, Erik Van Limbergen48, Sigrid Hatse48, Jenny Chang-Claude49, Anja Rudolph49, Petra Seibold49, Dieter Flesch-Janys49, Paolo Radice50, Paolo Peterlongo51, Bernardo Bonanni52, Sara Volorio53, Graham G Giles54, Gianluca Severi54, Laura Baglietto54, Catriona A McLean55, Christopher A Haiman56, Brian E Henderson56, Fredrick Schumacher56, Loic Le Marchand57, Jacques Simard58, Mark S Goldberg59, France Labrèche60, Martine Dumont58, Vessela Kristensen61, Robert Winqvist62, Katri Pylkäs62, Arja Jukkola-Vuorinen63, Saila Kauppila63, Irene L Andrulis64, Julia A Knight65, Gord Glendon66, Anna Marie Mulligan67, Peter Devillee68, Rob A E M Tollenaar69, Caroline M Seynaeve70, Mieke Kriege70, Jonine Figueroa71, Stephen J Chanock71, Mark E Sherman71, Maartje J Hooning72, Antoinette Hollestelle72, Ans M W van den Ouweland73, Carolien H M van Deurzen74, Jingmei Li75, Kamila Czene76, Keith Humphreys76, Angela Cox77, Simon S Cross78, Malcolm W R Reed77, Mitul Shah79, Anna Jakubowska80, Jan Lubinski80, Katarzyna Jaworska-Bieniek81, Katarzyna Durda80, Anthony Swerdlow82, Alan Ashworth83, Nicholas Orr83, Minouk Schoemaker3, Fergus J Couch84, Emily Hallberg85, Anna González-Neira86, Guillermo Pita86, M Rosario Alonso86, Daniel C Tessier87, Daniel Vincent87, Francois Bacot87, Manjeet K Bolla88, Qin Wang88, Joe Dennis88, Kyriaki Michailidou88, Alison M Dunning79, Per Hall76, Doug Easton88, Paul Pharoah89, Marjanka K Schmidt13, Ian Tomlinson90, Montserrat Garcia-Closas91.
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.Entities:
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Year: 2014 PMID： 24743323 PMCID： PMC3990493 DOI： 10.1371/journal.pgen.1004285
Source DB: PubMed Journal: PLoS Genet ISSN： 1553-7390 Impact factor: 5.917