Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2
Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutati...
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creator | Mulligan, Anna Marie Couch, Fergus J Barrowdale, Daniel Domchek, Susan M Eccles, Diana Nevanlinna, Heli Ramus, Susan J Robson, Mark Sherman, Mark Spurdle, Amanda B Wappenschmidt, Barbara Lee, Andrew McGuffog, Lesley Healey, Sue Sinilnikova, Olga M Janavicius, Ramunas Hansen, Thomas vO Nielsen, Finn C Ejlertsen, Bent Osorio, Ana Muñoz-Repeto, Iván Durán, Mercedes Godino, Javier Pertesi, Maroulio Benítez, Javier Peterlongo, Paolo Manoukian, Siranoush Peissel, Bernard Zaffaroni, Daniela Cattaneo, Elisa Bonanni, Bernardo Viel, Alessandra Pasini, Barbara Papi, Laura Ottini, Laura Savarese, Antonella Bernard, Loris Radice, Paolo Hamann, Ute Verheus, Martijn Meijers-Heijboer, Hanne E J Wijnen, Juul Gómez García, Encarna B Nelen, Marcel R Kets, C Marleen Seynaeve, Caroline Tilanus-Linthorst, Madeleine M A van der Luijt, Rob B van Os, Theo Rookus, Matti Frost, Debra Jones, J Louise Evans, D Gareth Lalloo, Fiona Eeles, Ros Izatt, Louise Adlard, Julian Davidson, Rosemarie Cook, Jackie Donaldson, Alan Dorkins, Huw Gregory, Helen Eason, Jacqueline Houghton, Catherine Barwell, Julian Side, Lucy E McCann, Emma Murray, Alex Peock, Susan Godwin, Andrew K Schmutzler, Rita K Rhiem, Kerstin Engel, Christoph Meindl, Alfons Ruehl, Ina Arnold, Norbert Niederacher, Dieter Sutter, Christian Deissler, Helmut Gadzicki, Dorothea Kast, Karin Preisler-Adams, Sabine Varon-Mateeva, Raymonda Schoenbuchner, Ines Fiebig, Britta Heinritz, Wolfram Schäfer, Dieter Gevensleben, Heidrun Caux-Moncoutier, Virginie Fassy-Colcombet, Marion Cornelis, François Mazoyer, Sylvie Léoné, Mélanie Boutry-Kryza, Nadia Hardouin, Agnès Berthet, Pascaline Muller, Danièle Fricker, Jean-Pierre Mortemousque, Isabelle Pujol, Pascal |
description | Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour.
We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach.
The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status.
The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers. |
doi_str_mv | 10.1186/bcr3052 |
format | Article |
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Couch, Fergus J ; Barrowdale, Daniel ; Domchek, Susan M ; Eccles, Diana ; Nevanlinna, Heli ; Ramus, Susan J ; Robson, Mark ; Sherman, Mark ; Spurdle, Amanda B ; Wappenschmidt, Barbara ; Lee, Andrew ; McGuffog, Lesley ; Healey, Sue ; Sinilnikova, Olga M ; Janavicius, Ramunas ; Hansen, Thomas vO ; Nielsen, Finn C ; Ejlertsen, Bent ; Osorio, Ana ; Muñoz-Repeto, Iván ; Durán, Mercedes ; Godino, Javier ; Pertesi, Maroulio ; Benítez, Javier ; Peterlongo, Paolo ; Manoukian, Siranoush ; Peissel, Bernard ; Zaffaroni, Daniela ; Cattaneo, Elisa ; Bonanni, Bernardo ; Viel, Alessandra ; Pasini, Barbara ; Papi, Laura ; Ottini, Laura ; Savarese, Antonella ; Bernard, Loris ; Radice, Paolo ; Hamann, Ute ; Verheus, Martijn ; Meijers-Heijboer, Hanne E J ; Wijnen, Juul ; Gómez García, Encarna B ; Nelen, Marcel R ; Kets, C Marleen ; Seynaeve, Caroline ; Tilanus-Linthorst, Madeleine M A ; van der Luijt, Rob B ; van Os, Theo ; Rookus, Matti ; Frost, Debra ; Jones, J Louise ; Evans, D Gareth ; Lalloo, Fiona ; Eeles, Ros ; Izatt, Louise ; Adlard, Julian ; Davidson, Rosemarie ; Cook, Jackie ; Donaldson, Alan ; Dorkins, Huw ; Gregory, Helen ; Eason, Jacqueline ; Houghton, Catherine ; Barwell, Julian ; Side, Lucy E ; McCann, Emma ; Murray, Alex ; Peock, Susan ; Godwin, Andrew K ; Schmutzler, Rita K ; Rhiem, Kerstin ; Engel, Christoph ; Meindl, Alfons ; Ruehl, Ina ; Arnold, Norbert ; Niederacher, Dieter ; Sutter, Christian ; Deissler, Helmut ; Gadzicki, Dorothea ; Kast, Karin ; Preisler-Adams, Sabine ; Varon-Mateeva, Raymonda ; Schoenbuchner, Ines ; Fiebig, Britta ; Heinritz, Wolfram ; Schäfer, Dieter ; Gevensleben, Heidrun ; Caux-Moncoutier, Virginie ; Fassy-Colcombet, Marion ; Cornelis, François ; Mazoyer, Sylvie ; Léoné, Mélanie ; Boutry-Kryza, Nadia ; Hardouin, Agnès ; Berthet, Pascaline ; Muller, Danièle ; Fricker, Jean-Pierre ; Mortemousque, Isabelle ; Pujol, Pascal</creator><creatorcontrib>Mulligan, Anna Marie ; Couch, Fergus J ; Barrowdale, Daniel ; Domchek, Susan M ; Eccles, Diana ; Nevanlinna, Heli ; Ramus, Susan J ; Robson, Mark ; Sherman, Mark ; Spurdle, Amanda B ; Wappenschmidt, Barbara ; Lee, Andrew ; McGuffog, Lesley ; Healey, Sue ; Sinilnikova, Olga M ; Janavicius, Ramunas ; Hansen, Thomas vO ; Nielsen, Finn C ; Ejlertsen, Bent ; Osorio, Ana ; Muñoz-Repeto, Iván ; Durán, Mercedes ; Godino, Javier ; Pertesi, Maroulio ; Benítez, Javier ; Peterlongo, Paolo ; Manoukian, Siranoush ; Peissel, Bernard ; Zaffaroni, Daniela ; Cattaneo, Elisa ; Bonanni, Bernardo ; Viel, Alessandra ; Pasini, Barbara ; Papi, Laura ; Ottini, Laura ; Savarese, Antonella ; Bernard, Loris ; Radice, Paolo ; Hamann, Ute ; Verheus, Martijn ; Meijers-Heijboer, Hanne E J ; Wijnen, Juul ; Gómez García, Encarna B ; Nelen, Marcel R ; Kets, C Marleen ; Seynaeve, Caroline ; Tilanus-Linthorst, Madeleine M A ; van der Luijt, Rob B ; van Os, Theo ; Rookus, Matti ; Frost, Debra ; Jones, J Louise ; Evans, D Gareth ; Lalloo, Fiona ; Eeles, Ros ; Izatt, Louise ; Adlard, Julian ; Davidson, Rosemarie ; Cook, Jackie ; Donaldson, Alan ; Dorkins, Huw ; Gregory, Helen ; Eason, Jacqueline ; Houghton, Catherine ; Barwell, Julian ; Side, Lucy E ; McCann, Emma ; Murray, Alex ; Peock, Susan ; Godwin, Andrew K ; Schmutzler, Rita K ; Rhiem, Kerstin ; Engel, Christoph ; Meindl, Alfons ; Ruehl, Ina ; Arnold, Norbert ; Niederacher, Dieter ; Sutter, Christian ; Deissler, Helmut ; Gadzicki, Dorothea ; Kast, Karin ; Preisler-Adams, Sabine ; Varon-Mateeva, Raymonda ; Schoenbuchner, Ines ; Fiebig, Britta ; Heinritz, Wolfram ; Schäfer, Dieter ; Gevensleben, Heidrun ; Caux-Moncoutier, Virginie ; Fassy-Colcombet, Marion ; Cornelis, François ; Mazoyer, Sylvie ; Léoné, Mélanie ; Boutry-Kryza, Nadia ; Hardouin, Agnès ; Berthet, Pascaline ; Muller, Danièle ; Fricker, Jean-Pierre ; Mortemousque, Isabelle ; Pujol, Pascal ; Ontario Cancer Genetics Network ; kConFab Investigators ; EMBRACE ; GEMO Study Collaborators ; CIMBA ; Breast Cancer Family Registry ; HEBON ; SWE-BRCA</creatorcontrib><description>Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour.
We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach.
The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status.
The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.</description><identifier>ISSN: 1465-542X</identifier><identifier>ISSN: 1465-5411</identifier><identifier>EISSN: 1465-542X</identifier><identifier>DOI: 10.1186/bcr3052</identifier><identifier>PMID: 22053997</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Alleles ; BRCA mutations ; Breast cancer ; Breast Neoplasms - classification ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Cancer ; Cancer and Oncology ; Cancer genetics ; Cancer och onkologi ; Cancer research ; Clinical Medicine ; Disease susceptibility ; Female ; Gene mutation ; Genes, BRCA1 ; Genes, BRCA2 ; Genetic aspects ; Genetic Predisposition to Disease ; Gynaecology, Obstetrics and Reproductive Medicine ; Gynekologi, obstetrik och reproduktionsmedicin ; Health aspects ; Heterozygote ; Humans ; Klinisk medicin ; Life Sciences ; Medical and Health Sciences ; Medicin och hälsovetenskap ; Mutation ; Polymorphism, Single Nucleotide ; Progesterone ; Receptors, Estrogen - metabolism ; Receptors, Progesterone - metabolism ; Risk ; SAMHÄLLSVETENSKAP ; Single nucleotide polymorphisms ; SOCIAL SCIENCES</subject><ispartof>Breast cancer research : BCR, 2011-01, Vol.13 (6), p.R110-R110, Article R110</ispartof><rights>COPYRIGHT 2011 BioMed Central Ltd.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright ©2011 Mulligan et al.; licensee BioMed Central Ltd. 2011 Mulligan et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c682t-c1bda43a3d6a0dee7bc3de51f802a8c88cbe66827ede4bbcd7a2088f499006a03</citedby><cites>FETCH-LOGICAL-c682t-c1bda43a3d6a0dee7bc3de51f802a8c88cbe66827ede4bbcd7a2088f499006a03</cites><orcidid>0000-0002-4678-2058 ; 0000-0002-5438-8309 ; 0000-0002-2135-0160</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326552/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326552/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,550,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22053997$$D View this record in 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Heli</creatorcontrib><creatorcontrib>Ramus, Susan J</creatorcontrib><creatorcontrib>Robson, Mark</creatorcontrib><creatorcontrib>Sherman, Mark</creatorcontrib><creatorcontrib>Spurdle, Amanda B</creatorcontrib><creatorcontrib>Wappenschmidt, Barbara</creatorcontrib><creatorcontrib>Lee, Andrew</creatorcontrib><creatorcontrib>McGuffog, Lesley</creatorcontrib><creatorcontrib>Healey, Sue</creatorcontrib><creatorcontrib>Sinilnikova, Olga M</creatorcontrib><creatorcontrib>Janavicius, Ramunas</creatorcontrib><creatorcontrib>Hansen, Thomas vO</creatorcontrib><creatorcontrib>Nielsen, Finn C</creatorcontrib><creatorcontrib>Ejlertsen, Bent</creatorcontrib><creatorcontrib>Osorio, Ana</creatorcontrib><creatorcontrib>Muñoz-Repeto, Iván</creatorcontrib><creatorcontrib>Durán, Mercedes</creatorcontrib><creatorcontrib>Godino, Javier</creatorcontrib><creatorcontrib>Pertesi, Maroulio</creatorcontrib><creatorcontrib>Benítez, Javier</creatorcontrib><creatorcontrib>Peterlongo, Paolo</creatorcontrib><creatorcontrib>Manoukian, Siranoush</creatorcontrib><creatorcontrib>Peissel, Bernard</creatorcontrib><creatorcontrib>Zaffaroni, Daniela</creatorcontrib><creatorcontrib>Cattaneo, Elisa</creatorcontrib><creatorcontrib>Bonanni, Bernardo</creatorcontrib><creatorcontrib>Viel, Alessandra</creatorcontrib><creatorcontrib>Pasini, Barbara</creatorcontrib><creatorcontrib>Papi, Laura</creatorcontrib><creatorcontrib>Ottini, Laura</creatorcontrib><creatorcontrib>Savarese, Antonella</creatorcontrib><creatorcontrib>Bernard, Loris</creatorcontrib><creatorcontrib>Radice, Paolo</creatorcontrib><creatorcontrib>Hamann, Ute</creatorcontrib><creatorcontrib>Verheus, Martijn</creatorcontrib><creatorcontrib>Meijers-Heijboer, Hanne E J</creatorcontrib><creatorcontrib>Wijnen, Juul</creatorcontrib><creatorcontrib>Gómez García, Encarna B</creatorcontrib><creatorcontrib>Nelen, Marcel R</creatorcontrib><creatorcontrib>Kets, C Marleen</creatorcontrib><creatorcontrib>Seynaeve, 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E</creatorcontrib><creatorcontrib>McCann, Emma</creatorcontrib><creatorcontrib>Murray, Alex</creatorcontrib><creatorcontrib>Peock, Susan</creatorcontrib><creatorcontrib>Godwin, Andrew K</creatorcontrib><creatorcontrib>Schmutzler, Rita K</creatorcontrib><creatorcontrib>Rhiem, Kerstin</creatorcontrib><creatorcontrib>Engel, Christoph</creatorcontrib><creatorcontrib>Meindl, Alfons</creatorcontrib><creatorcontrib>Ruehl, Ina</creatorcontrib><creatorcontrib>Arnold, Norbert</creatorcontrib><creatorcontrib>Niederacher, Dieter</creatorcontrib><creatorcontrib>Sutter, Christian</creatorcontrib><creatorcontrib>Deissler, Helmut</creatorcontrib><creatorcontrib>Gadzicki, Dorothea</creatorcontrib><creatorcontrib>Kast, Karin</creatorcontrib><creatorcontrib>Preisler-Adams, Sabine</creatorcontrib><creatorcontrib>Varon-Mateeva, Raymonda</creatorcontrib><creatorcontrib>Schoenbuchner, Ines</creatorcontrib><creatorcontrib>Fiebig, Britta</creatorcontrib><creatorcontrib>Heinritz, Wolfram</creatorcontrib><creatorcontrib>Schäfer, Dieter</creatorcontrib><creatorcontrib>Gevensleben, Heidrun</creatorcontrib><creatorcontrib>Caux-Moncoutier, Virginie</creatorcontrib><creatorcontrib>Fassy-Colcombet, Marion</creatorcontrib><creatorcontrib>Cornelis, François</creatorcontrib><creatorcontrib>Mazoyer, Sylvie</creatorcontrib><creatorcontrib>Léoné, Mélanie</creatorcontrib><creatorcontrib>Boutry-Kryza, Nadia</creatorcontrib><creatorcontrib>Hardouin, Agnès</creatorcontrib><creatorcontrib>Berthet, Pascaline</creatorcontrib><creatorcontrib>Muller, Danièle</creatorcontrib><creatorcontrib>Fricker, Jean-Pierre</creatorcontrib><creatorcontrib>Mortemousque, Isabelle</creatorcontrib><creatorcontrib>Pujol, Pascal</creatorcontrib><creatorcontrib>Ontario Cancer Genetics Network</creatorcontrib><creatorcontrib>kConFab Investigators</creatorcontrib><creatorcontrib>EMBRACE</creatorcontrib><creatorcontrib>GEMO Study Collaborators</creatorcontrib><creatorcontrib>CIMBA</creatorcontrib><creatorcontrib>Breast Cancer Family Registry</creatorcontrib><creatorcontrib>HEBON</creatorcontrib><creatorcontrib>SWE-BRCA</creatorcontrib><title>Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2</title><title>Breast cancer research : BCR</title><addtitle>Breast Cancer Res</addtitle><description>Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour.
We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach.
The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status.
The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.</description><subject>Alleles</subject><subject>BRCA mutations</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - classification</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Cancer</subject><subject>Cancer and Oncology</subject><subject>Cancer genetics</subject><subject>Cancer och onkologi</subject><subject>Cancer research</subject><subject>Clinical Medicine</subject><subject>Disease susceptibility</subject><subject>Female</subject><subject>Gene mutation</subject><subject>Genes, BRCA1</subject><subject>Genes, BRCA2</subject><subject>Genetic aspects</subject><subject>Genetic Predisposition to Disease</subject><subject>Gynaecology, Obstetrics and Reproductive Medicine</subject><subject>Gynekologi, obstetrik och reproduktionsmedicin</subject><subject>Health aspects</subject><subject>Heterozygote</subject><subject>Humans</subject><subject>Klinisk medicin</subject><subject>Life Sciences</subject><subject>Medical and Health Sciences</subject><subject>Medicin och hälsovetenskap</subject><subject>Mutation</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Progesterone</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Receptors, Progesterone - metabolism</subject><subject>Risk</subject><subject>SAMHÄLLSVETENSKAP</subject><subject>Single nucleotide polymorphisms</subject><subject>SOCIAL SCIENCES</subject><issn>1465-542X</issn><issn>1465-5411</issn><issn>1465-542X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp9k99u0zAUxiMEYmMg3gBZ4oIbutlOnDhcIJXyZ5OKkBAg7izbOWkNTlxsp1NfjafDacvUIjZFVk5Oft937JOcLHtK8DkhvLxQ2ueY0XvZKSlKNmEF_X7_ID7JHoXwA2NSccYfZieUYpbXdXWa_Z65rnM9Uh5kiEjLXoNHYQgaVtEoY03cIGktWAhIekAyBKeNjNCgaxOXKA6dG0aFiptVYkyP3nyeTQmSfbONKOqGKKNJRbT03oAPr5CHMNgYUOtdh-IS0Mz1wflohg65Fl31awjRLGR0PoyJj64x7SgdH7b-F_Rx9qCVNsCT_f0s-_r-3ZfZ5WT-6cPVbDqf6JLTONFENbLIZd6UEjcAldJ5A4y0HFPJNedaQZnIChoolNJNJSnmvC3qGuMkyc-yyc43XMNqUGLlTSf9RjhpxD71M0UgWIFrVid-fitvh1VaKq1RQKmsFcEgJPBSFG1bClXVjeBEYdAlyRnJ7yy_SHYptdi6EYZrQhP_8lb-rfk2Fc4vhDWDqEq6tX-9wxPbQaOhj17aI9Xxm94sxcKtRZ7TkrGDest_ZJfTuTB9AN-J1MgKl5isScJf7Ot592tIX1l0Jv1s1soe3BBEzXKKCavHPj7fkQtpITm1LtXXIy2mBU92nBd3U5RjQsqiqhJ1_h8qXQ10RrseWpPyR7b7bWrvQvDQ3hyNYDGOnNiPXCKfHTbwhvs7Y_kfET0pww</recordid><startdate>20110101</startdate><enddate>20110101</enddate><creator>Mulligan, Anna Marie</creator><creator>Couch, Fergus J</creator><creator>Barrowdale, Daniel</creator><creator>Domchek, Susan M</creator><creator>Eccles, Diana</creator><creator>Nevanlinna, Heli</creator><creator>Ramus, Susan J</creator><creator>Robson, Mark</creator><creator>Sherman, Mark</creator><creator>Spurdle, Amanda B</creator><creator>Wappenschmidt, Barbara</creator><creator>Lee, Andrew</creator><creator>McGuffog, Lesley</creator><creator>Healey, Sue</creator><creator>Sinilnikova, Olga M</creator><creator>Janavicius, Ramunas</creator><creator>Hansen, Thomas vO</creator><creator>Nielsen, Finn C</creator><creator>Ejlertsen, Bent</creator><creator>Osorio, Ana</creator><creator>Muñoz-Repeto, Iván</creator><creator>Durán, Mercedes</creator><creator>Godino, Javier</creator><creator>Pertesi, Maroulio</creator><creator>Benítez, Javier</creator><creator>Peterlongo, Paolo</creator><creator>Manoukian, Siranoush</creator><creator>Peissel, Bernard</creator><creator>Zaffaroni, Daniela</creator><creator>Cattaneo, Elisa</creator><creator>Bonanni, Bernardo</creator><creator>Viel, Alessandra</creator><creator>Pasini, Barbara</creator><creator>Papi, Laura</creator><creator>Ottini, Laura</creator><creator>Savarese, Antonella</creator><creator>Bernard, Loris</creator><creator>Radice, Paolo</creator><creator>Hamann, Ute</creator><creator>Verheus, Martijn</creator><creator>Meijers-Heijboer, Hanne E J</creator><creator>Wijnen, Juul</creator><creator>Gómez García, Encarna B</creator><creator>Nelen, Marcel R</creator><creator>Kets, C Marleen</creator><creator>Seynaeve, Caroline</creator><creator>Tilanus-Linthorst, Madeleine M A</creator><creator>van der Luijt, Rob B</creator><creator>van Os, Theo</creator><creator>Rookus, Matti</creator><creator>Frost, Debra</creator><creator>Jones, J Louise</creator><creator>Evans, D Gareth</creator><creator>Lalloo, Fiona</creator><creator>Eeles, Ros</creator><creator>Izatt, Louise</creator><creator>Adlard, 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Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><scope>ABXSW</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>DG8</scope><scope>ZZAVC</scope><scope>F1U</scope><scope>AGCHP</scope><scope>D95</scope><orcidid>https://orcid.org/0000-0002-4678-2058</orcidid><orcidid>https://orcid.org/0000-0002-5438-8309</orcidid><orcidid>https://orcid.org/0000-0002-2135-0160</orcidid></search><sort><creationdate>20110101</creationdate><title>Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2</title><author>Mulligan, Anna Marie ; Couch, Fergus J ; Barrowdale, Daniel ; Domchek, Susan M ; Eccles, Diana ; Nevanlinna, Heli ; Ramus, Susan J ; Robson, Mark ; Sherman, Mark ; Spurdle, Amanda B ; Wappenschmidt, Barbara ; Lee, Andrew ; McGuffog, Lesley ; Healey, Sue ; Sinilnikova, Olga M ; Janavicius, Ramunas ; Hansen, Thomas vO ; Nielsen, Finn C ; Ejlertsen, Bent ; Osorio, Ana ; Muñoz-Repeto, Iván ; Durán, Mercedes ; Godino, Javier ; Pertesi, Maroulio ; Benítez, Javier ; Peterlongo, Paolo ; Manoukian, Siranoush ; Peissel, Bernard ; Zaffaroni, Daniela ; Cattaneo, Elisa ; Bonanni, Bernardo ; Viel, Alessandra ; Pasini, Barbara ; Papi, Laura ; Ottini, Laura ; Savarese, Antonella ; Bernard, Loris ; Radice, Paolo ; Hamann, Ute ; Verheus, Martijn ; Meijers-Heijboer, Hanne E J ; Wijnen, Juul ; Gómez García, Encarna B ; Nelen, Marcel R ; Kets, C Marleen ; Seynaeve, Caroline ; Tilanus-Linthorst, Madeleine M A ; van der Luijt, Rob B ; van Os, Theo ; Rookus, Matti ; Frost, Debra ; Jones, J Louise ; Evans, D Gareth ; Lalloo, Fiona ; Eeles, Ros ; Izatt, Louise ; Adlard, Julian ; Davidson, Rosemarie ; Cook, Jackie ; Donaldson, Alan ; Dorkins, Huw ; Gregory, Helen ; Eason, Jacqueline ; Houghton, Catherine ; Barwell, Julian ; Side, Lucy E ; McCann, Emma ; Murray, Alex ; Peock, Susan ; Godwin, Andrew K ; Schmutzler, Rita K ; Rhiem, Kerstin ; Engel, Christoph ; Meindl, Alfons ; Ruehl, Ina ; Arnold, Norbert ; Niederacher, Dieter ; Sutter, Christian ; Deissler, Helmut ; Gadzicki, Dorothea ; Kast, Karin ; Preisler-Adams, Sabine ; Varon-Mateeva, Raymonda ; Schoenbuchner, Ines ; Fiebig, Britta ; Heinritz, Wolfram ; Schäfer, Dieter ; Gevensleben, Heidrun ; Caux-Moncoutier, Virginie ; Fassy-Colcombet, Marion ; Cornelis, François ; Mazoyer, Sylvie ; Léoné, Mélanie ; Boutry-Kryza, Nadia ; Hardouin, Agnès ; Berthet, Pascaline ; Muller, Danièle ; Fricker, Jean-Pierre ; Mortemousque, Isabelle ; Pujol, Pascal</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c682t-c1bda43a3d6a0dee7bc3de51f802a8c88cbe66827ede4bbcd7a2088f499006a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Alleles</topic><topic>BRCA mutations</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - classification</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Cancer</topic><topic>Cancer and Oncology</topic><topic>Cancer genetics</topic><topic>Cancer och onkologi</topic><topic>Cancer research</topic><topic>Clinical Medicine</topic><topic>Disease susceptibility</topic><topic>Female</topic><topic>Gene mutation</topic><topic>Genes, BRCA1</topic><topic>Genes, BRCA2</topic><topic>Genetic aspects</topic><topic>Genetic Predisposition to Disease</topic><topic>Gynaecology, Obstetrics and Reproductive Medicine</topic><topic>Gynekologi, obstetrik och 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Registry</creatorcontrib><creatorcontrib>HEBON</creatorcontrib><creatorcontrib>SWE-BRCA</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SWEPUB Linköpings universitet full text</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SWEPUB Linköpings universitet</collection><collection>SwePub Articles full text</collection><collection>SWEPUB Göteborgs universitet</collection><collection>SWEPUB Lunds universitet full text</collection><collection>SWEPUB Lunds universitet</collection><jtitle>Breast cancer research : BCR</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mulligan, Anna Marie</au><au>Couch, Fergus J</au><au>Barrowdale, Daniel</au><au>Domchek, Susan M</au><au>Eccles, Diana</au><au>Nevanlinna, Heli</au><au>Ramus, Susan J</au><au>Robson, Mark</au><au>Sherman, Mark</au><au>Spurdle, Amanda B</au><au>Wappenschmidt, Barbara</au><au>Lee, Andrew</au><au>McGuffog, Lesley</au><au>Healey, Sue</au><au>Sinilnikova, Olga M</au><au>Janavicius, Ramunas</au><au>Hansen, Thomas vO</au><au>Nielsen, Finn C</au><au>Ejlertsen, Bent</au><au>Osorio, Ana</au><au>Muñoz-Repeto, Iván</au><au>Durán, Mercedes</au><au>Godino, Javier</au><au>Pertesi, Maroulio</au><au>Benítez, Javier</au><au>Peterlongo, Paolo</au><au>Manoukian, Siranoush</au><au>Peissel, Bernard</au><au>Zaffaroni, Daniela</au><au>Cattaneo, Elisa</au><au>Bonanni, Bernardo</au><au>Viel, Alessandra</au><au>Pasini, Barbara</au><au>Papi, Laura</au><au>Ottini, Laura</au><au>Savarese, Antonella</au><au>Bernard, Loris</au><au>Radice, Paolo</au><au>Hamann, Ute</au><au>Verheus, Martijn</au><au>Meijers-Heijboer, Hanne E J</au><au>Wijnen, Juul</au><au>Gómez García, Encarna B</au><au>Nelen, Marcel R</au><au>Kets, C Marleen</au><au>Seynaeve, Caroline</au><au>Tilanus-Linthorst, Madeleine M A</au><au>van der Luijt, Rob B</au><au>van Os, Theo</au><au>Rookus, Matti</au><au>Frost, Debra</au><au>Jones, J Louise</au><au>Evans, D Gareth</au><au>Lalloo, Fiona</au><au>Eeles, Ros</au><au>Izatt, Louise</au><au>Adlard, Julian</au><au>Davidson, Rosemarie</au><au>Cook, Jackie</au><au>Donaldson, Alan</au><au>Dorkins, Huw</au><au>Gregory, Helen</au><au>Eason, Jacqueline</au><au>Houghton, Catherine</au><au>Barwell, Julian</au><au>Side, Lucy E</au><au>McCann, Emma</au><au>Murray, Alex</au><au>Peock, Susan</au><au>Godwin, Andrew K</au><au>Schmutzler, Rita K</au><au>Rhiem, Kerstin</au><au>Engel, Christoph</au><au>Meindl, Alfons</au><au>Ruehl, Ina</au><au>Arnold, Norbert</au><au>Niederacher, Dieter</au><au>Sutter, Christian</au><au>Deissler, Helmut</au><au>Gadzicki, Dorothea</au><au>Kast, Karin</au><au>Preisler-Adams, Sabine</au><au>Varon-Mateeva, Raymonda</au><au>Schoenbuchner, Ines</au><au>Fiebig, Britta</au><au>Heinritz, Wolfram</au><au>Schäfer, Dieter</au><au>Gevensleben, Heidrun</au><au>Caux-Moncoutier, Virginie</au><au>Fassy-Colcombet, Marion</au><au>Cornelis, François</au><au>Mazoyer, Sylvie</au><au>Léoné, Mélanie</au><au>Boutry-Kryza, Nadia</au><au>Hardouin, Agnès</au><au>Berthet, Pascaline</au><au>Muller, Danièle</au><au>Fricker, Jean-Pierre</au><au>Mortemousque, Isabelle</au><au>Pujol, Pascal</au><aucorp>Ontario Cancer Genetics Network</aucorp><aucorp>kConFab Investigators</aucorp><aucorp>EMBRACE</aucorp><aucorp>GEMO Study Collaborators</aucorp><aucorp>CIMBA</aucorp><aucorp>Breast Cancer Family Registry</aucorp><aucorp>HEBON</aucorp><aucorp>SWE-BRCA</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2</atitle><jtitle>Breast cancer research : BCR</jtitle><addtitle>Breast Cancer Res</addtitle><date>2011-01-01</date><risdate>2011</risdate><volume>13</volume><issue>6</issue><spage>R110</spage><epage>R110</epage><pages>R110-R110</pages><artnum>R110</artnum><issn>1465-542X</issn><issn>1465-5411</issn><eissn>1465-542X</eissn><abstract>Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour.
We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach.
The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status.
The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>22053997</pmid><doi>10.1186/bcr3052</doi><orcidid>https://orcid.org/0000-0002-4678-2058</orcidid><orcidid>https://orcid.org/0000-0002-5438-8309</orcidid><orcidid>https://orcid.org/0000-0002-2135-0160</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1465-542X |
ispartof | Breast cancer research : BCR, 2011-01, Vol.13 (6), p.R110-R110, Article R110 |
issn | 1465-542X 1465-5411 1465-542X |
language | eng |
recordid | cdi_swepub_primary_oai_swepub_ki_se_540959 |
source | MEDLINE; DOAJ Directory of Open Access Journals; SpringerLink Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SWEPUB Freely available online; PubMed Central Open Access; Springer Nature OA Free Journals |
subjects | Alleles BRCA mutations Breast cancer Breast Neoplasms - classification Breast Neoplasms - genetics Breast Neoplasms - metabolism Cancer Cancer and Oncology Cancer genetics Cancer och onkologi Cancer research Clinical Medicine Disease susceptibility Female Gene mutation Genes, BRCA1 Genes, BRCA2 Genetic aspects Genetic Predisposition to Disease Gynaecology, Obstetrics and Reproductive Medicine Gynekologi, obstetrik och reproduktionsmedicin Health aspects Heterozygote Humans Klinisk medicin Life Sciences Medical and Health Sciences Medicin och hälsovetenskap Mutation Polymorphism, Single Nucleotide Progesterone Receptors, Estrogen - metabolism Receptors, Progesterone - metabolism Risk SAMHÄLLSVETENSKAP Single nucleotide polymorphisms SOCIAL SCIENCES |
title | Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 |
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