Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers

Juliet D. French, Maya Ghoussaini, Stacey L. Edwards, Kerstin B. Meyer, Kyriaki Michailidou, Shahana Ahmed, Sofia Khan, Mel J. Maranian, Martin O'Reilly, Kristine M. Hillman, Joshua A. Betts, Thomas Carroll, Peter J. Bailey, Ed Dicks, Jonathan Beesley, Jonathan Tyrer, Ana Teresa Maia, Andrew Beck, Nicholas W. Knoblauch, Constance Chen & 191 others Peter Kraft, Daniel Barnes, Anna González-Neira, M. Rosario Alonso, Daniel Herrero, Daniel C. Tessier, Daniel Vincent, Francois Bacot, Craig Luccarini, Caroline Baynes, Don Conroy, Joe Dennis, Manjeet K. Bolla, Qin Wang, John L. Hopper, Melissa C. Southey, Marjanka K. Schmidt, Annegien Broeks, Senno Verhoef, Sten Cornelissen, Kenneth Muir, Artitaya Lophatananon, Sarah Stewart-Brown, Pornthep Siriwanarangsan, Peter A. Fasching, Christian R. Loehberg, Arif B. Ekici, Matthias W. Beckmann, Julian Peto, Isabel Dos Santos Silva, Nichola Johnson, Zoe Aitken, Elinor J. Sawyer, Ian Tomlinson, Michael J. Kerin, Nicola Miller, Frederik Marme, Andreas Schneeweiss, Christof Sohn, Barbara Burwinkel, Pascal Guénel, Thérèse Truong, Pierre Laurent-Puig, Florence Menegaux, Stig E. Bojesen, Børge G. Nordestgaard, Sune F. Nielsen, Henrik Flyger, Roger L. Milne, M. Pilar Zamora, Jose Ignacio Arias Perez, Javier Benitez, Hoda Anton-Culver, Hermann Brenner, Heiko Müller, Volker Arndt, Christa Stegmaier, Alfons Meindl, Peter Lichtner, Rita K. Schmutzler, Christoph Engel, Hiltrud Brauch, Ute Hamann, Christina Justenhoven, Kirsimari Aaltonen, Päivi Heikkilä, Kristiina Aittomäki, Carl Blomqvist, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Aiko Sueta, Natalia V. Bogdanova, Natalia N. Antonenkova, Thilo Dörk, Annika Lindblom, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli Matti Kosma, Jaana M. Hartikainen, Anna H. Wu, Chiu Chen Tseng, David Van Den Berg, Daniel O. Stram, Diether Lambrechts, Stephanie Peeters, Ann Smeets, Giuseppe Floris, Jenny Chang-Claude, Anja Rudolph, Stefan Nickels, Dieter Flesch-Janys, Paolo Radice, Paolo Peterlongo, Bernardo Bonanni, Domenico Sardella, Fergus J Couch, Xianshu Wang, Vernon S. Pankratz, Adam Lee, Graham G. Giles, Gianluca Severi, Laura Baglietto, Christopher A. Haiman, Brian E. Henderson, Fredrick Schumacher, Loic Le Marchand, Jacques Simard, Mark S. Goldberg, France Labrèche, Martine Dumont, Soo Hwang Teo, Cheng Har Yip, Char Hong Ng, Eranga Nishanthie Vithana, Vessela Kristensen, Wei Zheng, Sandra Deming-Halverson, Martha Shrubsole, Jirong Long, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L. Andrulis, Julia A. Knight, Gord Glendon, Anna Marie Mulligan, Peter Devilee, Caroline Seynaeve, Montserrat García-Closas, Jonine Figueroa, Stephen J. Chanock, Jolanta Lissowska, Kamila Czene, Daniel Klevebring, Nils Schoof, Maartje J. Hooning, John W M Martens, J. Margriet Collée, Madeleine Tilanus-Linthorst, Per Hall, Jingmei Li, Jianjun Liu, Keith Humphreys, Xiao Ou Shu, Wei Lu, Yu Tang Gao, Hui Cai, Angela Cox, Sabapathy P. Balasubramanian, William Blot, Lisa B. Signorello, Qiuyin Cai, Paul D P Pharoah, Catherine S. Healey, Mitul Shah, Karen A. Pooley, Daehee Kang, Keun Young Yoo, Dong Young Noh, Mikael Hartman, Hui Miao, Jen Hwei Sng, Xueling Sim, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Suleeporn Sangrajrang, Valerie Gaborieau, James McKay, Amanda E. Toland, Christine B. Ambrosone, Drakoulis Yannoukakos, Andrew K. Godwin, Chen Yang Shen, Chia Ni Hsiung, Pei Ei Wu, Shou Tung Chen, Anthony Swerdlow, Alan Ashworth, Nick Orr, Minouk J. Schoemaker, Bruce A J Ponder, Heli Nevanlinna, Melissa A. Brown, Georgia Chenevix-Trench, Douglas F. Easton, Alison M. Dunning

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1.

Original languageEnglish (US)
Pages (from-to)489-503
Number of pages15
JournalAmerican Journal of Human Genetics
Volume92
Issue number4
DOIs
StatePublished - Apr 4 2013

Fingerprint

Cyclin D1
Transcriptional Silencer Elements
Breast Neoplasms
Luciferases
Estrogen Receptors
Chromatin
Case-Control Studies
Neoplasms
Transcription Factors
Alleles
Binding Sites
Genes
Proteins

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

French, J. D., Ghoussaini, M., Edwards, S. L., Meyer, K. B., Michailidou, K., Ahmed, S., ... Dunning, A. M. (2013). Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers. American Journal of Human Genetics, 92(4), 489-503. https://doi.org/10.1016/j.ajhg.2013.01.002

Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers. / French, Juliet D.; Ghoussaini, Maya; Edwards, Stacey L.; Meyer, Kerstin B.; Michailidou, Kyriaki; Ahmed, Shahana; Khan, Sofia; Maranian, Mel J.; O'Reilly, Martin; Hillman, Kristine M.; Betts, Joshua A.; Carroll, Thomas; Bailey, Peter J.; Dicks, Ed; Beesley, Jonathan; Tyrer, Jonathan; Maia, Ana Teresa; Beck, Andrew; Knoblauch, Nicholas W.; Chen, Constance; Kraft, Peter; Barnes, Daniel; González-Neira, Anna; Alonso, M. Rosario; Herrero, Daniel; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Conroy, Don; Dennis, Joe; Bolla, Manjeet K.; Wang, Qin; Hopper, John L.; Southey, Melissa C.; Schmidt, Marjanka K.; Broeks, Annegien; Verhoef, Senno; Cornelissen, Sten; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Loehberg, Christian R.; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; Dos Santos Silva, Isabel; Johnson, Nichola; Aitken, Zoe; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Zamora, M. Pilar; Arias Perez, Jose Ignacio; Benitez, Javier; Anton-Culver, Hoda; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K.; Engel, Christoph; Brauch, Hiltrud; Hamann, Ute; Justenhoven, Christina; Aaltonen, Kirsimari; Heikkilä, Päivi; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Sueta, Aiko; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli Matti; Hartikainen, Jaana M.; Wu, Anna H.; Tseng, Chiu Chen; Van Den Berg, David; Stram, Daniel O.; Lambrechts, Diether; Peeters, Stephanie; Smeets, Ann; Floris, Giuseppe; Chang-Claude, Jenny; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Sardella, Domenico; Couch, Fergus J; Wang, Xianshu; Pankratz, Vernon S.; Lee, Adam; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; Ng, Char Hong; Vithana, Eranga Nishanthie; Kristensen, Vessela; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Devilee, Peter; Seynaeve, Caroline; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J.; Lissowska, Jolanta; Czene, Kamila; Klevebring, Daniel; Schoof, Nils; Hooning, Maartje J.; Martens, John W M; Collée, J. Margriet; Tilanus-Linthorst, Madeleine; Hall, Per; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao Ou; Lu, Wei; Gao, Yu Tang; Cai, Hui; Cox, Angela; Balasubramanian, Sabapathy P.; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Pharoah, Paul D P; Healey, Catherine S.; Shah, Mitul; Pooley, Karen A.; Kang, Daehee; Yoo, Keun Young; Noh, Dong Young; Hartman, Mikael; Miao, Hui; Sng, Jen Hwei; Sim, Xueling; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; McKay, James; Toland, Amanda E.; Ambrosone, Christine B.; Yannoukakos, Drakoulis; Godwin, Andrew K.; Shen, Chen Yang; Hsiung, Chia Ni; Wu, Pei Ei; Chen, Shou Tung; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J.; Ponder, Bruce A J; Nevanlinna, Heli; Brown, Melissa A.; Chenevix-Trench, Georgia; Easton, Douglas F.; Dunning, Alison M.

In: American Journal of Human Genetics, Vol. 92, No. 4, 04.04.2013, p. 489-503.

Research output: Contribution to journalArticle

French, JD, Ghoussaini, M, Edwards, SL, Meyer, KB, Michailidou, K, Ahmed, S, Khan, S, Maranian, MJ, O'Reilly, M, Hillman, KM, Betts, JA, Carroll, T, Bailey, PJ, Dicks, E, Beesley, J, Tyrer, J, Maia, AT, Beck, A, Knoblauch, NW, Chen, C, Kraft, P, Barnes, D, González-Neira, A, Alonso, MR, Herrero, D, Tessier, DC, Vincent, D, Bacot, F, Luccarini, C, Baynes, C, Conroy, D, Dennis, J, Bolla, MK, Wang, Q, Hopper, JL, Southey, MC, Schmidt, MK, Broeks, A, Verhoef, S, Cornelissen, S, Muir, K, Lophatananon, A, Stewart-Brown, S, Siriwanarangsan, P, Fasching, PA, Loehberg, CR, Ekici, AB, Beckmann, MW, Peto, J, Dos Santos Silva, I, Johnson, N, Aitken, Z, Sawyer, EJ, Tomlinson, I, Kerin, MJ, Miller, N, Marme, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Guénel, P, Truong, T, Laurent-Puig, P, Menegaux, F, Bojesen, SE, Nordestgaard, BG, Nielsen, SF, Flyger, H, Milne, RL, Zamora, MP, Arias Perez, JI, Benitez, J, Anton-Culver, H, Brenner, H, Müller, H, Arndt, V, Stegmaier, C, Meindl, A, Lichtner, P, Schmutzler, RK, Engel, C, Brauch, H, Hamann, U, Justenhoven, C, Aaltonen, K, Heikkilä, P, Aittomäki, K, Blomqvist, C, Matsuo, K, Ito, H, Iwata, H, Sueta, A, Bogdanova, NV, Antonenkova, NN, Dörk, T, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, JM, Wu, AH, Tseng, CC, Van Den Berg, D, Stram, DO, Lambrechts, D, Peeters, S, Smeets, A, Floris, G, Chang-Claude, J, Rudolph, A, Nickels, S, Flesch-Janys, D, Radice, P, Peterlongo, P, Bonanni, B, Sardella, D, Couch, FJ, Wang, X, Pankratz, VS, Lee, A, Giles, GG, Severi, G, Baglietto, L, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Simard, J, Goldberg, MS, Labrèche, F, Dumont, M, Teo, SH, Yip, CH, Ng, CH, Vithana, EN, Kristensen, V, Zheng, W, Deming-Halverson, S, Shrubsole, M, Long, J, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Devilee, P, Seynaeve, C, García-Closas, M, Figueroa, J, Chanock, SJ, Lissowska, J, Czene, K, Klevebring, D, Schoof, N, Hooning, MJ, Martens, JWM, Collée, JM, Tilanus-Linthorst, M, Hall, P, Li, J, Liu, J, Humphreys, K, Shu, XO, Lu, W, Gao, YT, Cai, H, Cox, A, Balasubramanian, SP, Blot, W, Signorello, LB, Cai, Q, Pharoah, PDP, Healey, CS, Shah, M, Pooley, KA, Kang, D, Yoo, KY, Noh, DY, Hartman, M, Miao, H, Sng, JH, Sim, X, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Sangrajrang, S, Gaborieau, V, McKay, J, Toland, AE, Ambrosone, CB, Yannoukakos, D, Godwin, AK, Shen, CY, Hsiung, CN, Wu, PE, Chen, ST, Swerdlow, A, Ashworth, A, Orr, N, Schoemaker, MJ, Ponder, BAJ, Nevanlinna, H, Brown, MA, Chenevix-Trench, G, Easton, DF & Dunning, AM 2013, 'Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers', American Journal of Human Genetics, vol. 92, no. 4, pp. 489-503. https://doi.org/10.1016/j.ajhg.2013.01.002
French, Juliet D. ; Ghoussaini, Maya ; Edwards, Stacey L. ; Meyer, Kerstin B. ; Michailidou, Kyriaki ; Ahmed, Shahana ; Khan, Sofia ; Maranian, Mel J. ; O'Reilly, Martin ; Hillman, Kristine M. ; Betts, Joshua A. ; Carroll, Thomas ; Bailey, Peter J. ; Dicks, Ed ; Beesley, Jonathan ; Tyrer, Jonathan ; Maia, Ana Teresa ; Beck, Andrew ; Knoblauch, Nicholas W. ; Chen, Constance ; Kraft, Peter ; Barnes, Daniel ; González-Neira, Anna ; Alonso, M. Rosario ; Herrero, Daniel ; Tessier, Daniel C. ; Vincent, Daniel ; Bacot, Francois ; Luccarini, Craig ; Baynes, Caroline ; Conroy, Don ; Dennis, Joe ; Bolla, Manjeet K. ; Wang, Qin ; Hopper, John L. ; Southey, Melissa C. ; Schmidt, Marjanka K. ; Broeks, Annegien ; Verhoef, Senno ; Cornelissen, Sten ; Muir, Kenneth ; Lophatananon, Artitaya ; Stewart-Brown, Sarah ; Siriwanarangsan, Pornthep ; Fasching, Peter A. ; Loehberg, Christian R. ; Ekici, Arif B. ; Beckmann, Matthias W. ; Peto, Julian ; Dos Santos Silva, Isabel ; Johnson, Nichola ; Aitken, Zoe ; Sawyer, Elinor J. ; Tomlinson, Ian ; Kerin, Michael J. ; Miller, Nicola ; Marme, Frederik ; Schneeweiss, Andreas ; Sohn, Christof ; Burwinkel, Barbara ; Guénel, Pascal ; Truong, Thérèse ; Laurent-Puig, Pierre ; Menegaux, Florence ; Bojesen, Stig E. ; Nordestgaard, Børge G. ; Nielsen, Sune F. ; Flyger, Henrik ; Milne, Roger L. ; Zamora, M. Pilar ; Arias Perez, Jose Ignacio ; Benitez, Javier ; Anton-Culver, Hoda ; Brenner, Hermann ; Müller, Heiko ; Arndt, Volker ; Stegmaier, Christa ; Meindl, Alfons ; Lichtner, Peter ; Schmutzler, Rita K. ; Engel, Christoph ; Brauch, Hiltrud ; Hamann, Ute ; Justenhoven, Christina ; Aaltonen, Kirsimari ; Heikkilä, Päivi ; Aittomäki, Kristiina ; Blomqvist, Carl ; Matsuo, Keitaro ; Ito, Hidemi ; Iwata, Hiroji ; Sueta, Aiko ; Bogdanova, Natalia V. ; Antonenkova, Natalia N. ; Dörk, Thilo ; Lindblom, Annika ; Margolin, Sara ; Mannermaa, Arto ; Kataja, Vesa ; Kosma, Veli Matti ; Hartikainen, Jaana M. ; Wu, Anna H. ; Tseng, Chiu Chen ; Van Den Berg, David ; Stram, Daniel O. ; Lambrechts, Diether ; Peeters, Stephanie ; Smeets, Ann ; Floris, Giuseppe ; Chang-Claude, Jenny ; Rudolph, Anja ; Nickels, Stefan ; Flesch-Janys, Dieter ; Radice, Paolo ; Peterlongo, Paolo ; Bonanni, Bernardo ; Sardella, Domenico ; Couch, Fergus J ; Wang, Xianshu ; Pankratz, Vernon S. ; Lee, Adam ; Giles, Graham G. ; Severi, Gianluca ; Baglietto, Laura ; Haiman, Christopher A. ; Henderson, Brian E. ; Schumacher, Fredrick ; Le Marchand, Loic ; Simard, Jacques ; Goldberg, Mark S. ; Labrèche, France ; Dumont, Martine ; Teo, Soo Hwang ; Yip, Cheng Har ; Ng, Char Hong ; Vithana, Eranga Nishanthie ; Kristensen, Vessela ; Zheng, Wei ; Deming-Halverson, Sandra ; Shrubsole, Martha ; Long, Jirong ; Winqvist, Robert ; Pylkäs, Katri ; Jukkola-Vuorinen, Arja ; Grip, Mervi ; Andrulis, Irene L. ; Knight, Julia A. ; Glendon, Gord ; Mulligan, Anna Marie ; Devilee, Peter ; Seynaeve, Caroline ; García-Closas, Montserrat ; Figueroa, Jonine ; Chanock, Stephen J. ; Lissowska, Jolanta ; Czene, Kamila ; Klevebring, Daniel ; Schoof, Nils ; Hooning, Maartje J. ; Martens, John W M ; Collée, J. Margriet ; Tilanus-Linthorst, Madeleine ; Hall, Per ; Li, Jingmei ; Liu, Jianjun ; Humphreys, Keith ; Shu, Xiao Ou ; Lu, Wei ; Gao, Yu Tang ; Cai, Hui ; Cox, Angela ; Balasubramanian, Sabapathy P. ; Blot, William ; Signorello, Lisa B. ; Cai, Qiuyin ; Pharoah, Paul D P ; Healey, Catherine S. ; Shah, Mitul ; Pooley, Karen A. ; Kang, Daehee ; Yoo, Keun Young ; Noh, Dong Young ; Hartman, Mikael ; Miao, Hui ; Sng, Jen Hwei ; Sim, Xueling ; Jakubowska, Anna ; Lubinski, Jan ; Jaworska-Bieniek, Katarzyna ; Durda, Katarzyna ; Sangrajrang, Suleeporn ; Gaborieau, Valerie ; McKay, James ; Toland, Amanda E. ; Ambrosone, Christine B. ; Yannoukakos, Drakoulis ; Godwin, Andrew K. ; Shen, Chen Yang ; Hsiung, Chia Ni ; Wu, Pei Ei ; Chen, Shou Tung ; Swerdlow, Anthony ; Ashworth, Alan ; Orr, Nick ; Schoemaker, Minouk J. ; Ponder, Bruce A J ; Nevanlinna, Heli ; Brown, Melissa A. ; Chenevix-Trench, Georgia ; Easton, Douglas F. ; Dunning, Alison M. / Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers. In: American Journal of Human Genetics. 2013 ; Vol. 92, No. 4. pp. 489-503.
@article{eb43858a79554977ade77e9c75cdf250,
title = "Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers",
abstract = "Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1.",
author = "French, {Juliet D.} and Maya Ghoussaini and Edwards, {Stacey L.} and Meyer, {Kerstin B.} and Kyriaki Michailidou and Shahana Ahmed and Sofia Khan and Maranian, {Mel J.} and Martin O'Reilly and Hillman, {Kristine M.} and Betts, {Joshua A.} and Thomas Carroll and Bailey, {Peter J.} and Ed Dicks and Jonathan Beesley and Jonathan Tyrer and Maia, {Ana Teresa} and Andrew Beck and Knoblauch, {Nicholas W.} and Constance Chen and Peter Kraft and Daniel Barnes and Anna Gonz{\'a}lez-Neira and Alonso, {M. Rosario} and Daniel Herrero and Tessier, {Daniel C.} and Daniel Vincent and Francois Bacot and Craig Luccarini and Caroline Baynes and Don Conroy and Joe Dennis and Bolla, {Manjeet K.} and Qin Wang and Hopper, {John L.} and Southey, {Melissa C.} and Schmidt, {Marjanka K.} and Annegien Broeks and Senno Verhoef and Sten Cornelissen and Kenneth Muir and Artitaya Lophatananon and Sarah Stewart-Brown and Pornthep Siriwanarangsan and Fasching, {Peter A.} and Loehberg, {Christian R.} and Ekici, {Arif B.} and Beckmann, {Matthias W.} and Julian Peto and {Dos Santos Silva}, Isabel and Nichola Johnson and Zoe Aitken and Sawyer, {Elinor J.} and Ian Tomlinson and Kerin, {Michael J.} and Nicola Miller and Frederik Marme and Andreas Schneeweiss and Christof Sohn and Barbara Burwinkel and Pascal Gu{\'e}nel and Th{\'e}r{\`e}se Truong and Pierre Laurent-Puig and Florence Menegaux and Bojesen, {Stig E.} and Nordestgaard, {B{\o}rge G.} and Nielsen, {Sune F.} and Henrik Flyger and Milne, {Roger L.} and Zamora, {M. Pilar} and {Arias Perez}, {Jose Ignacio} and Javier Benitez and Hoda Anton-Culver and Hermann Brenner and Heiko M{\"u}ller and Volker Arndt and Christa Stegmaier and Alfons Meindl and Peter Lichtner and Schmutzler, {Rita K.} and Christoph Engel and Hiltrud Brauch and Ute Hamann and Christina Justenhoven and Kirsimari Aaltonen and P{\"a}ivi Heikkil{\"a} and Kristiina Aittom{\"a}ki and Carl Blomqvist and Keitaro Matsuo and Hidemi Ito and Hiroji Iwata and Aiko Sueta and Bogdanova, {Natalia V.} and Antonenkova, {Natalia N.} and Thilo D{\"o}rk and Annika Lindblom and Sara Margolin and Arto Mannermaa and Vesa Kataja and Kosma, {Veli Matti} and Hartikainen, {Jaana M.} and Wu, {Anna H.} and Tseng, {Chiu Chen} and {Van Den Berg}, David and Stram, {Daniel O.} and Diether Lambrechts and Stephanie Peeters and Ann Smeets and Giuseppe Floris and Jenny Chang-Claude and Anja Rudolph and Stefan Nickels and Dieter Flesch-Janys and Paolo Radice and Paolo Peterlongo and Bernardo Bonanni and Domenico Sardella and Couch, {Fergus J} and Xianshu Wang and Pankratz, {Vernon S.} and Adam Lee and Giles, {Graham G.} and Gianluca Severi and Laura Baglietto and Haiman, {Christopher A.} and Henderson, {Brian E.} and Fredrick Schumacher and {Le Marchand}, Loic and Jacques Simard and Goldberg, {Mark S.} and France Labr{\`e}che and Martine Dumont and Teo, {Soo Hwang} and Yip, {Cheng Har} and Ng, {Char Hong} and Vithana, {Eranga Nishanthie} and Vessela Kristensen and Wei Zheng and Sandra Deming-Halverson and Martha Shrubsole and Jirong Long and Robert Winqvist and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Mervi Grip and Andrulis, {Irene L.} and Knight, {Julia A.} and Gord Glendon and Mulligan, {Anna Marie} and Peter Devilee and Caroline Seynaeve and Montserrat Garc{\'i}a-Closas and Jonine Figueroa and Chanock, {Stephen J.} and Jolanta Lissowska and Kamila Czene and Daniel Klevebring and Nils Schoof and Hooning, {Maartje J.} and Martens, {John W M} and Coll{\'e}e, {J. Margriet} and Madeleine Tilanus-Linthorst and Per Hall and Jingmei Li and Jianjun Liu and Keith Humphreys and Shu, {Xiao Ou} and Wei Lu and Gao, {Yu Tang} and Hui Cai and Angela Cox and Balasubramanian, {Sabapathy P.} and William Blot and Signorello, {Lisa B.} and Qiuyin Cai and Pharoah, {Paul D P} and Healey, {Catherine S.} and Mitul Shah and Pooley, {Karen A.} and Daehee Kang and Yoo, {Keun Young} and Noh, {Dong Young} and Mikael Hartman and Hui Miao and Sng, {Jen Hwei} and Xueling Sim and Anna Jakubowska and Jan Lubinski and Katarzyna Jaworska-Bieniek and Katarzyna Durda and Suleeporn Sangrajrang and Valerie Gaborieau and James McKay and Toland, {Amanda E.} and Ambrosone, {Christine B.} and Drakoulis Yannoukakos and Godwin, {Andrew K.} and Shen, {Chen Yang} and Hsiung, {Chia Ni} and Wu, {Pei Ei} and Chen, {Shou Tung} and Anthony Swerdlow and Alan Ashworth and Nick Orr and Schoemaker, {Minouk J.} and Ponder, {Bruce A J} and Heli Nevanlinna and Brown, {Melissa A.} and Georgia Chenevix-Trench and Easton, {Douglas F.} and Dunning, {Alison M.}",
year = "2013",
month = "4",
day = "4",
doi = "10.1016/j.ajhg.2013.01.002",
language = "English (US)",
volume = "92",
pages = "489--503",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers

AU - French, Juliet D.

AU - Ghoussaini, Maya

AU - Edwards, Stacey L.

AU - Meyer, Kerstin B.

AU - Michailidou, Kyriaki

AU - Ahmed, Shahana

AU - Khan, Sofia

AU - Maranian, Mel J.

AU - O'Reilly, Martin

AU - Hillman, Kristine M.

AU - Betts, Joshua A.

AU - Carroll, Thomas

AU - Bailey, Peter J.

AU - Dicks, Ed

AU - Beesley, Jonathan

AU - Tyrer, Jonathan

AU - Maia, Ana Teresa

AU - Beck, Andrew

AU - Knoblauch, Nicholas W.

AU - Chen, Constance

AU - Kraft, Peter

AU - Barnes, Daniel

AU - González-Neira, Anna

AU - Alonso, M. Rosario

AU - Herrero, Daniel

AU - Tessier, Daniel C.

AU - Vincent, Daniel

AU - Bacot, Francois

AU - Luccarini, Craig

AU - Baynes, Caroline

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PY - 2013/4/4

Y1 - 2013/4/4

N2 - Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1.

AB - Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1.

UR - http://www.scopus.com/inward/record.url?scp=84875933011&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875933011&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2013.01.002

DO - 10.1016/j.ajhg.2013.01.002

M3 - Article

VL - 92

SP - 489

EP - 503

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 4

ER -