Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast: e1004285
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...
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| creator | Sawyer, Elinor Petridis, Christos Brook, Mark N Papouli, Efterpi Fletcher, Olivia Pinder, Sarah Peto, Julian Johnson, Nichola Dwek, Miriam Houlston, Richard Ieso, Paolo De Southey, Melissa C Provenzano, Elena Apicella, Carmel Wesseling, Jelle Cornelissen, Sten Keeman, Renske Ekici, Arif B Beckmann, Matthias W Kerin, Michael J Marme, Federick Schneeweiss, Andreas Sohn, Christof Burwinkel, Barbara Guénel, Pascal Laurent-Puig, Pierre Kerbrat, Pierre Nordestgaard, Børge G Nielsen, Sune F Flyger, Henrik Milne, Roger L Menéndez, Primitiva Benitez, Javier Brenner, Hermann Arndt, Volker Schmutzler, Rita K Lochmann, Magdalena Ko, Yon-Dschun Nevanlinna, Heli Muranen, Taru A Margolin, Sara Kataja, Vesa Hartikainen, Jaana M Chenevix-Trench, Georgia Lambrechts, Diether Limbergen, Erik Van Rudolph, Anja Seibold, Petra Flesch-Janys, Dieter Radice, Paolo Peterlongo, Paolo Bonanni, Bernardo Giles, Graham G Severi, Gianluca Baglietto, Laura Mclean, Catriona A Henderson, Brian E Schumacher, Fredrick Marchand, Loic Le Simard, Jacques Labrèche, France Dumont, Martine Pylkäs, Katri Kauppila, Saila Andrulis, Irene L Knight, Julia A Glendon, Gord Mulligan, Anna Marie Devillee, Peter Tollenaar, A EM Seynaeve, Caroline M Kriege, Mieke Figueroa, Jonine Chanock, Stephen J Sherman, Mark E Hollestelle, Antoinette Czene, Kamila Cross, Simon S Reed, Malcolm WR Shah, Mitul Jakubowska, Anna Lubinski, Jan Jaworska-Bieniek, Katarzyna Swerdlow, Anthony Orr, Nicholas Schoemaker, Minouk Couch, Fergus J Hallberg, Emily Tessier, Daniel C Vincent, Daniel Bacot, Francois Bolla, Manjeet K Wang, Qin Dunning, Alison M Hall, Per Easton, Doug Pharoah, Paul Schmidt, Marjanka K Tomlinson, Ian Garcia-Closas, Montserrat |
| description | 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 |
| doi_str_mv | 10.1371/journal.pgen.1004285 |
| format | Article |
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Petridis, Christos ; Brook, Mark N ; Papouli, Efterpi ; Fletcher, Olivia ; Pinder, Sarah ; Peto, Julian ; Johnson, Nichola ; Dwek, Miriam ; Houlston, Richard ; Ieso, Paolo De ; Southey, Melissa C ; Provenzano, Elena ; Apicella, Carmel ; Wesseling, Jelle ; Cornelissen, Sten ; Keeman, Renske ; Ekici, Arif B ; Beckmann, Matthias W ; Kerin, Michael J ; Marme, Federick ; Schneeweiss, Andreas ; Sohn, Christof ; Burwinkel, Barbara ; Guénel, Pascal ; Laurent-Puig, Pierre ; Kerbrat, Pierre ; Nordestgaard, Børge G ; Nielsen, Sune F ; Flyger, Henrik ; Milne, Roger L ; Menéndez, Primitiva ; Benitez, Javier ; Brenner, Hermann ; Arndt, Volker ; Schmutzler, Rita K ; Lochmann, Magdalena ; Ko, Yon-Dschun ; Nevanlinna, Heli ; Muranen, Taru A ; Margolin, Sara ; Kataja, Vesa ; Hartikainen, Jaana M ; Chenevix-Trench, Georgia ; Lambrechts, Diether ; Limbergen, Erik Van ; Rudolph, Anja ; Seibold, Petra ; Flesch-Janys, Dieter ; Radice, Paolo ; Peterlongo, Paolo ; Bonanni, Bernardo ; Giles, Graham G ; Severi, Gianluca ; Baglietto, Laura ; Mclean, Catriona A ; Henderson, Brian E ; Schumacher, Fredrick ; Marchand, Loic Le ; Simard, Jacques ; Labrèche, France ; Dumont, Martine ; Pylkäs, Katri ; Kauppila, Saila ; Andrulis, Irene L ; Knight, Julia A ; Glendon, Gord ; Mulligan, Anna Marie ; Devillee, Peter ; Tollenaar, A EM ; Seynaeve, Caroline M ; Kriege, Mieke ; Figueroa, Jonine ; Chanock, Stephen J ; Sherman, Mark E ; Hollestelle, Antoinette ; Czene, Kamila ; Cross, Simon S ; Reed, Malcolm WR ; Shah, Mitul ; Jakubowska, Anna ; Lubinski, Jan ; Jaworska-Bieniek, Katarzyna ; Swerdlow, Anthony ; Orr, Nicholas ; Schoemaker, Minouk ; Couch, Fergus J ; Hallberg, Emily ; Tessier, Daniel C ; Vincent, Daniel ; Bacot, Francois ; Bolla, Manjeet K ; Wang, Qin ; Dunning, Alison M ; Hall, Per ; Easton, Doug ; Pharoah, Paul ; Schmidt, Marjanka K ; Tomlinson, Ian ; Garcia-Closas, Montserrat</creator><creatorcontrib>Sawyer, Elinor ; Petridis, Christos ; Brook, Mark N ; Papouli, Efterpi ; Fletcher, Olivia ; Pinder, Sarah ; Peto, Julian ; Johnson, Nichola ; Dwek, Miriam ; Houlston, Richard ; Ieso, Paolo De ; Southey, Melissa C ; Provenzano, Elena ; Apicella, Carmel ; Wesseling, Jelle ; Cornelissen, Sten ; Keeman, Renske ; Ekici, Arif B ; Beckmann, Matthias W ; Kerin, Michael J ; Marme, Federick ; Schneeweiss, Andreas ; Sohn, Christof ; Burwinkel, Barbara ; Guénel, Pascal ; Laurent-Puig, Pierre ; Kerbrat, Pierre ; Nordestgaard, Børge G ; Nielsen, Sune F ; Flyger, Henrik ; Milne, Roger L ; Menéndez, Primitiva ; Benitez, Javier ; Brenner, Hermann ; Arndt, Volker ; Schmutzler, Rita K ; Lochmann, Magdalena ; Ko, Yon-Dschun ; Nevanlinna, Heli ; Muranen, Taru A ; Margolin, Sara ; Kataja, Vesa ; Hartikainen, Jaana M ; Chenevix-Trench, Georgia ; Lambrechts, Diether ; Limbergen, Erik Van ; Rudolph, Anja ; Seibold, Petra ; Flesch-Janys, Dieter ; Radice, Paolo ; Peterlongo, Paolo ; Bonanni, Bernardo ; Giles, Graham G ; Severi, Gianluca ; Baglietto, Laura ; Mclean, Catriona A ; Henderson, Brian E ; Schumacher, Fredrick ; Marchand, Loic Le ; Simard, Jacques ; Labrèche, France ; Dumont, Martine ; Pylkäs, Katri ; Kauppila, Saila ; Andrulis, Irene L ; Knight, Julia A ; Glendon, Gord ; Mulligan, Anna Marie ; Devillee, Peter ; Tollenaar, A EM ; Seynaeve, Caroline M ; Kriege, Mieke ; Figueroa, Jonine ; Chanock, Stephen J ; Sherman, Mark E ; Hollestelle, Antoinette ; Czene, Kamila ; Cross, Simon S ; Reed, Malcolm WR ; Shah, Mitul ; Jakubowska, Anna ; Lubinski, Jan ; Jaworska-Bieniek, Katarzyna ; Swerdlow, Anthony ; Orr, Nicholas ; Schoemaker, Minouk ; Couch, Fergus J ; Hallberg, Emily ; Tessier, Daniel C ; Vincent, Daniel ; Bacot, Francois ; Bolla, Manjeet K ; Wang, Qin ; Dunning, Alison M ; Hall, Per ; Easton, Doug ; Pharoah, Paul ; Schmidt, Marjanka K ; Tomlinson, Ian ; Garcia-Closas, Montserrat</creatorcontrib><description>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.</description><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1004285</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Biomedical research ; Breast cancer ; Councils ; Genomes ; Grants ; Medical research ; Studies ; Tumors</subject><ispartof>PLoS genetics, 2014-04, Vol.10 (4)</ispartof><rights>2014 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Citation: Sawyer E, Roylance R, Petridis C, Brook MN, Nowinski S, et al. (2014) Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast. 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Mieke</creatorcontrib><creatorcontrib>Figueroa, Jonine</creatorcontrib><creatorcontrib>Chanock, Stephen J</creatorcontrib><creatorcontrib>Sherman, Mark E</creatorcontrib><creatorcontrib>Hollestelle, Antoinette</creatorcontrib><creatorcontrib>Czene, Kamila</creatorcontrib><creatorcontrib>Cross, Simon S</creatorcontrib><creatorcontrib>Reed, Malcolm WR</creatorcontrib><creatorcontrib>Shah, Mitul</creatorcontrib><creatorcontrib>Jakubowska, Anna</creatorcontrib><creatorcontrib>Lubinski, Jan</creatorcontrib><creatorcontrib>Jaworska-Bieniek, Katarzyna</creatorcontrib><creatorcontrib>Swerdlow, Anthony</creatorcontrib><creatorcontrib>Orr, Nicholas</creatorcontrib><creatorcontrib>Schoemaker, Minouk</creatorcontrib><creatorcontrib>Couch, Fergus J</creatorcontrib><creatorcontrib>Hallberg, Emily</creatorcontrib><creatorcontrib>Tessier, Daniel C</creatorcontrib><creatorcontrib>Vincent, Daniel</creatorcontrib><creatorcontrib>Bacot, Francois</creatorcontrib><creatorcontrib>Bolla, Manjeet K</creatorcontrib><creatorcontrib>Wang, Qin</creatorcontrib><creatorcontrib>Dunning, Alison M</creatorcontrib><creatorcontrib>Hall, Per</creatorcontrib><creatorcontrib>Easton, Doug</creatorcontrib><creatorcontrib>Pharoah, Paul</creatorcontrib><creatorcontrib>Schmidt, Marjanka K</creatorcontrib><creatorcontrib>Tomlinson, Ian</creatorcontrib><creatorcontrib>Garcia-Closas, Montserrat</creatorcontrib><title>Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast: e1004285</title><title>PLoS genetics</title><description>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.</description><subject>Biomedical research</subject><subject>Breast cancer</subject><subject>Councils</subject><subject>Genomes</subject><subject>Grants</subject><subject>Medical 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Brook, Mark N ; Papouli, Efterpi ; Fletcher, Olivia ; Pinder, Sarah ; Peto, Julian ; Johnson, Nichola ; Dwek, Miriam ; Houlston, Richard ; Ieso, Paolo De ; Southey, Melissa C ; Provenzano, Elena ; Apicella, Carmel ; Wesseling, Jelle ; Cornelissen, Sten ; Keeman, Renske ; Ekici, Arif B ; Beckmann, Matthias W ; Kerin, Michael J ; Marme, Federick ; Schneeweiss, Andreas ; Sohn, Christof ; Burwinkel, Barbara ; Guénel, Pascal ; Laurent-Puig, Pierre ; Kerbrat, Pierre ; Nordestgaard, Børge G ; Nielsen, Sune F ; Flyger, Henrik ; Milne, Roger L ; Menéndez, Primitiva ; Benitez, Javier ; Brenner, Hermann ; Arndt, Volker ; Schmutzler, Rita K ; Lochmann, Magdalena ; Ko, Yon-Dschun ; Nevanlinna, Heli ; Muranen, Taru A ; Margolin, Sara ; Kataja, Vesa ; Hartikainen, Jaana M ; Chenevix-Trench, Georgia ; Lambrechts, Diether ; Limbergen, Erik Van ; Rudolph, Anja ; Seibold, Petra ; Flesch-Janys, Dieter ; Radice, Paolo ; Peterlongo, Paolo ; Bonanni, Bernardo ; Giles, Graham G ; Severi, Gianluca ; Baglietto, Laura ; Mclean, Catriona A ; Henderson, Brian E ; Schumacher, Fredrick ; Marchand, Loic Le ; Simard, Jacques ; Labrèche, France ; Dumont, Martine ; Pylkäs, Katri ; Kauppila, Saila ; Andrulis, Irene L ; Knight, Julia A ; Glendon, Gord ; Mulligan, Anna Marie ; Devillee, Peter ; Tollenaar, A EM ; Seynaeve, Caroline M ; Kriege, Mieke ; Figueroa, Jonine ; Chanock, Stephen J ; Sherman, Mark E ; Hollestelle, Antoinette ; Czene, Kamila ; Cross, Simon S ; Reed, Malcolm WR ; Shah, Mitul ; Jakubowska, Anna ; Lubinski, Jan ; Jaworska-Bieniek, Katarzyna ; Swerdlow, Anthony ; Orr, Nicholas ; Schoemaker, Minouk ; Couch, Fergus J ; Hallberg, Emily ; Tessier, Daniel C ; Vincent, Daniel ; Bacot, Francois ; Bolla, Manjeet K ; Wang, Qin ; Dunning, Alison M ; Hall, Per ; Easton, Doug ; Pharoah, Paul ; Schmidt, Marjanka K ; Tomlinson, Ian ; Garcia-Closas, Montserrat</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p619-a30caaa1ec58e3452288a46ad0d0831e895e4d397b9d3eaf3cacf37773c5ca653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Biomedical research</topic><topic>Breast cancer</topic><topic>Councils</topic><topic>Genomes</topic><topic>Grants</topic><topic>Medical research</topic><topic>Studies</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sawyer, Elinor</creatorcontrib><creatorcontrib>Petridis, Christos</creatorcontrib><creatorcontrib>Brook, Mark N</creatorcontrib><creatorcontrib>Papouli, Efterpi</creatorcontrib><creatorcontrib>Fletcher, Olivia</creatorcontrib><creatorcontrib>Pinder, Sarah</creatorcontrib><creatorcontrib>Peto, Julian</creatorcontrib><creatorcontrib>Johnson, Nichola</creatorcontrib><creatorcontrib>Dwek, 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genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sawyer, Elinor</au><au>Petridis, Christos</au><au>Brook, Mark N</au><au>Papouli, Efterpi</au><au>Fletcher, Olivia</au><au>Pinder, Sarah</au><au>Peto, Julian</au><au>Johnson, Nichola</au><au>Dwek, Miriam</au><au>Houlston, Richard</au><au>Ieso, Paolo De</au><au>Southey, Melissa C</au><au>Provenzano, Elena</au><au>Apicella, Carmel</au><au>Wesseling, Jelle</au><au>Cornelissen, Sten</au><au>Keeman, Renske</au><au>Ekici, Arif B</au><au>Beckmann, Matthias W</au><au>Kerin, Michael J</au><au>Marme, Federick</au><au>Schneeweiss, Andreas</au><au>Sohn, Christof</au><au>Burwinkel, Barbara</au><au>Guénel, Pascal</au><au>Laurent-Puig, Pierre</au><au>Kerbrat, Pierre</au><au>Nordestgaard, Børge G</au><au>Nielsen, Sune F</au><au>Flyger, Henrik</au><au>Milne, Roger L</au><au>Menéndez, Primitiva</au><au>Benitez, Javier</au><au>Brenner, Hermann</au><au>Arndt, Volker</au><au>Schmutzler, Rita K</au><au>Lochmann, Magdalena</au><au>Ko, Yon-Dschun</au><au>Nevanlinna, Heli</au><au>Muranen, Taru A</au><au>Margolin, Sara</au><au>Kataja, Vesa</au><au>Hartikainen, Jaana M</au><au>Chenevix-Trench, Georgia</au><au>Lambrechts, Diether</au><au>Limbergen, Erik Van</au><au>Rudolph, Anja</au><au>Seibold, Petra</au><au>Flesch-Janys, Dieter</au><au>Radice, Paolo</au><au>Peterlongo, Paolo</au><au>Bonanni, Bernardo</au><au>Giles, Graham G</au><au>Severi, Gianluca</au><au>Baglietto, Laura</au><au>Mclean, Catriona A</au><au>Henderson, Brian E</au><au>Schumacher, Fredrick</au><au>Marchand, Loic Le</au><au>Simard, Jacques</au><au>Labrèche, France</au><au>Dumont, Martine</au><au>Pylkäs, Katri</au><au>Kauppila, Saila</au><au>Andrulis, Irene L</au><au>Knight, Julia A</au><au>Glendon, Gord</au><au>Mulligan, Anna Marie</au><au>Devillee, Peter</au><au>Tollenaar, A EM</au><au>Seynaeve, Caroline M</au><au>Kriege, Mieke</au><au>Figueroa, Jonine</au><au>Chanock, Stephen J</au><au>Sherman, Mark E</au><au>Hollestelle, Antoinette</au><au>Czene, Kamila</au><au>Cross, Simon S</au><au>Reed, Malcolm WR</au><au>Shah, Mitul</au><au>Jakubowska, Anna</au><au>Lubinski, Jan</au><au>Jaworska-Bieniek, Katarzyna</au><au>Swerdlow, Anthony</au><au>Orr, Nicholas</au><au>Schoemaker, Minouk</au><au>Couch, Fergus J</au><au>Hallberg, Emily</au><au>Tessier, Daniel C</au><au>Vincent, Daniel</au><au>Bacot, Francois</au><au>Bolla, Manjeet K</au><au>Wang, Qin</au><au>Dunning, Alison M</au><au>Hall, Per</au><au>Easton, Doug</au><au>Pharoah, Paul</au><au>Schmidt, Marjanka K</au><au>Tomlinson, Ian</au><au>Garcia-Closas, Montserrat</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast: e1004285</atitle><jtitle>PLoS genetics</jtitle><date>2014-04-01</date><risdate>2014</risdate><volume>10</volume><issue>4</issue><issn>1553-7390</issn><eissn>1553-7404</eissn><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.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><doi>10.1371/journal.pgen.1004285</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1553-7390 |
| ispartof | PLoS genetics, 2014-04, Vol.10 (4) |
| issn | 1553-7390 1553-7404 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1534825309 |
| source | DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Public Library of Science (PLoS) |
| subjects | Biomedical research Breast cancer Councils Genomes Grants Medical research Studies Tumors |
| title | Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast: e1004285 |
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