Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation

Ghoussaini, Maya, Edwards, Stacey L., Michailidou, Kyriaki, Nord, Silje, Lari, Richard Cowper-Sal, Desai, Kinjal, Kar, Siddhartha, Hillman, Kristine M., Kaufmann, Susanne, Glubb, Dylan M., Beesley, Jonathan, Dennis, Joe, Bolla, Manjeet K., Wang, Qin, Dicks, Ed, Guo, Qi, Schmidt, Marjanka K., Shah, Mitul, Luben, Robert, Brown, Judith, Czene, Kamila, Darabi, Hatef, Eriksson, Mikael, Klevebring, Daniel, Bojesen, Stig E., Nordestgaard, Borge G., Nielsen, Sune F., Flyger, Henrik, Lambrechts, Diether, Thienpont, Bernard, Neven, Patrick, Wildiers, Hans, Broeks, Annegien, Van't Veer, Laura J., Rutgers, Emiel J. Th, Couch, Fergus J., Olson, Janet E., Hallberg, Emily, Vachon, Celine, Chang-Claude, Jenny, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Peto, Julian, dos-Santos-Silva, Isabel, Gibson, Lorna, Nevanlinna, Heli, Muranen, Taru A., Aittomaki, Kristiina, Blomqvist, Carl, Hall, Per, Li, Jingmei, Liu, Jianjun, Humphreys, Keith, Kang, Daehee, Choi, Ji-Yeob, Park, Sue K., Noh, Dong-Young, Matsuo, Keitaro, Ito, Hidemi, Iwata, Hiroji, Yatabe, Yasushi, Guenel, Pascal, Truong, Therese, Menegaux, Florence, Sanchez, Marie, Burwinkel, Barbara, Marme, Frederik, Schneeweiss, Andreas, Sohn, Christof, Wu, Anna H., Tseng, Chiu-Chen, Van Den Berg, David, Stram, Daniel O., Benitez, Javier, Pilar Zamora, M., Arias Perez, Jose Ignacio, Menendez, Primitiva, Shu, Xiao-Ou, Lu, Wei, Gao, Yu-Tang, Cai, Qiuyin, Cox, Angela, Cross, Simon S., Reed, Malcolm W. R., Andrulis, Irene L., Knight, Julia A., Glendon, Gord, Tchatchou, Sandrine, Sawyer, Elinor J., Tomlinson, Ian, Kerin, Michael J., Miller, Nicola, Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick, Le Marchand, Loic, Lindblom, Annika, Margolin, Sara, Teo, Soo Hwang, Yip, Cheng Har, Lee, Daphne S. C., Wong, Tien Y., Hooning, Maartje J., Martens, John W. M., Collee, J. Margriet, van Deurzen, Carolien H. M., Hopper, John L., Southey, Melissa C., Tsimiklis, Helen, Kapuscinski, Miroslav K., Shen, Chen-Yang, Wu, Pei-Ei, Yu, Jyh-Cherng, Chen, Shou-Tung, Alnaes, Grethe Grenaker, Borresen-Dale, Anne-Lise, Giles, Graham G., Milne, Roger L., McLean, Catriona, Muir, Kenneth, Lophatananon, Artitaya, Stewart-Brown, Sarah, Siriwanarangsan, Pornthep, Hartman, Mikael, Miao, Hui, Buhari, Shaik Ahmad Bin Syed, Teo, Yik Ying, Fasching, Peter A., Haeberle, Lothar, Ekici, Arif B., Beckmann, Matthias W., Brenner, Hermann, Dieffenbach, Aida Karina, Arndt, Volker, Stegmaier, Christa, Swerdlow, Anthony, Ashworth, Alan, Orr, Nick, Schoemaker, Minouk J., Garcia-Closas, Montserrat, Figueroa, Jonine, Chanock, Stephen J., Lissowska, Jolanta, Simard, Jacques, Goldberg, Mark S., Labreche, France, Dumont, Martine, Winqvist, Robert, Pylkas, Katri, Jukkola-Vuorinen, Arja, Brauch, Hiltrud, Bruening, Thomas, Koto, Yon-Dschun, Radice, Paolo, Peterlongo, Paolo, Bonanni, Bernardo, Volorio, Sara, Doerk, Thilo, Bogdanova, Natalia V., Helbig, Sonja, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M., Devilee, Peter, Tollenaar, Robert A. E. M., Seynaeve, Caroline, Van Asperen, Christi J., Jakubowska, Anna, Lubinski, Jan, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Slager, Susan, Toland, Amanda E., Ambrosone, Christine B., Yannoukakos, Drakoulis, Sangrajrang, Suleeporn, Gaborieau, Valerie, Brennan, Paul, Mckay, James, Hamann, Ute, Torres, Diana, Zheng, Wei, Long, Jirong, Anton-Culver, Hoda, Neuhausen, Susan L., Luccarini, Craig, Baynes, Caroline, Ahmed, Shahana, Maranian, Mel, Healey, Catherine S., Gonzalez-Neira, Anna, Pita, Guillermo, Alonso, M. Rosario, Alvarez, Nuria, Herrero, Daniel, Tessier, Daniel C., Vincent, Daniel, Bacot, Francois, de Santiago, Ines, Carroll, Jason, Caldas, Carlos, Brown, Melissa A., Lupien, Mathieu, Kristensen, Vessela N., Pharoah, Paul D. P., Chenevix-Trench, Georgia, French, Juliet D., Easton, Douglas F. and Dunning, Alison M. (2014) Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation. Nature Communications, 4 4999.1-4999.12. doi:10.1038/ncomms5999

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Author Ghoussaini, Maya
Edwards, Stacey L.
Michailidou, Kyriaki
Nord, Silje
Lari, Richard Cowper-Sal
Desai, Kinjal
Kar, Siddhartha
Hillman, Kristine M.
Kaufmann, Susanne
Glubb, Dylan M.
Beesley, Jonathan
Dennis, Joe
Bolla, Manjeet K.
Wang, Qin
Dicks, Ed
Guo, Qi
Schmidt, Marjanka K.
Shah, Mitul
Luben, Robert
Brown, Judith
Czene, Kamila
Darabi, Hatef
Eriksson, Mikael
Klevebring, Daniel
Bojesen, Stig E.
Nordestgaard, Borge G.
Nielsen, Sune F.
Flyger, Henrik
Lambrechts, Diether
Thienpont, Bernard
Neven, Patrick
Wildiers, Hans
Broeks, Annegien
Van't Veer, Laura J.
Rutgers, Emiel J. Th
Couch, Fergus J.
Olson, Janet E.
Hallberg, Emily
Vachon, Celine
Chang-Claude, Jenny
Rudolph, Anja
Seibold, Petra
Flesch-Janys, Dieter
Peto, Julian
dos-Santos-Silva, Isabel
Gibson, Lorna
Nevanlinna, Heli
Muranen, Taru A.
Aittomaki, Kristiina
Blomqvist, Carl
Hall, Per
Li, Jingmei
Liu, Jianjun
Humphreys, Keith
Kang, Daehee
Choi, Ji-Yeob
Park, Sue K.
Noh, Dong-Young
Matsuo, Keitaro
Ito, Hidemi
Iwata, Hiroji
Yatabe, Yasushi
Guenel, Pascal
Truong, Therese
Menegaux, Florence
Sanchez, Marie
Burwinkel, Barbara
Marme, Frederik
Schneeweiss, Andreas
Sohn, Christof
Wu, Anna H.
Tseng, Chiu-Chen
Van Den Berg, David
Stram, Daniel O.
Benitez, Javier
Pilar Zamora, M.
Arias Perez, Jose Ignacio
Menendez, Primitiva
Shu, Xiao-Ou
Lu, Wei
Gao, Yu-Tang
Cai, Qiuyin
Cox, Angela
Cross, Simon S.
Reed, Malcolm W. R.
Andrulis, Irene L.
Knight, Julia A.
Glendon, Gord
Tchatchou, Sandrine
Sawyer, Elinor J.
Tomlinson, Ian
Kerin, Michael J.
Miller, Nicola
Haiman, Christopher A.
Henderson, Brian E.
Schumacher, Fredrick
Le Marchand, Loic
Lindblom, Annika
Margolin, Sara
Teo, Soo Hwang
Yip, Cheng Har
Lee, Daphne S. C.
Wong, Tien Y.
Hooning, Maartje J.
Martens, John W. M.
Collee, J. Margriet
van Deurzen, Carolien H. M.
Hopper, John L.
Southey, Melissa C.
Tsimiklis, Helen
Kapuscinski, Miroslav K.
Shen, Chen-Yang
Wu, Pei-Ei
Yu, Jyh-Cherng
Chen, Shou-Tung
Alnaes, Grethe Grenaker
Borresen-Dale, Anne-Lise
Giles, Graham G.
Milne, Roger L.
McLean, Catriona
Muir, Kenneth
Lophatananon, Artitaya
Stewart-Brown, Sarah
Siriwanarangsan, Pornthep
Hartman, Mikael
Miao, Hui
Buhari, Shaik Ahmad Bin Syed
Teo, Yik Ying
Fasching, Peter A.
Haeberle, Lothar
Ekici, Arif B.
Beckmann, Matthias W.
Brenner, Hermann
Dieffenbach, Aida Karina
Arndt, Volker
Stegmaier, Christa
Swerdlow, Anthony
Ashworth, Alan
Orr, Nick
Schoemaker, Minouk J.
Garcia-Closas, Montserrat
Figueroa, Jonine
Chanock, Stephen J.
Lissowska, Jolanta
Simard, Jacques
Goldberg, Mark S.
Labreche, France
Dumont, Martine
Winqvist, Robert
Pylkas, Katri
Jukkola-Vuorinen, Arja
Brauch, Hiltrud
Bruening, Thomas
Koto, Yon-Dschun
Radice, Paolo
Peterlongo, Paolo
Bonanni, Bernardo
Volorio, Sara
Doerk, Thilo
Bogdanova, Natalia V.
Helbig, Sonja
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana M.
Devilee, Peter
Tollenaar, Robert A. E. M.
Seynaeve, Caroline
Van Asperen, Christi J.
Jakubowska, Anna
Lubinski, Jan
Jaworska-Bieniek, Katarzyna
Durda, Katarzyna
Slager, Susan
Toland, Amanda E.
Ambrosone, Christine B.
Yannoukakos, Drakoulis
Sangrajrang, Suleeporn
Gaborieau, Valerie
Brennan, Paul
Mckay, James
Hamann, Ute
Torres, Diana
Zheng, Wei
Long, Jirong
Anton-Culver, Hoda
Neuhausen, Susan L.
Luccarini, Craig
Baynes, Caroline
Ahmed, Shahana
Maranian, Mel
Healey, Catherine S.
Gonzalez-Neira, Anna
Pita, Guillermo
Alonso, M. Rosario
Alvarez, Nuria
Herrero, Daniel
Tessier, Daniel C.
Vincent, Daniel
Bacot, Francois
de Santiago, Ines
Carroll, Jason
Caldas, Carlos
Brown, Melissa A.
Lupien, Mathieu
Kristensen, Vessela N.
Pharoah, Paul D. P.
Chenevix-Trench, Georgia
French, Juliet D.
Easton, Douglas F.
Dunning, Alison M.
Title Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation
Formatted title
Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2014-09
Year available 2014
Sub-type Article (original research)
DOI 10.1038/ncomms5999
Open Access Status File (Publisher version)
Volume 4
Start page 4999.1
End page 4999.12
Total pages 12
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2015
Language eng
Formatted abstract
GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the ‘iCOGS’ genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with ​oestrogen receptor positive (​ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84−0.87; P=1.7 × 10−43) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of ​IGFBP5 (encoding ​insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, ​FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of ​IGFBP5, a gene with known roles in breast cell biology.
Keyword Factor-binding protein-5
Cyclin D1 expression
In-Vivo
Functional variants
Growth
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
School of Medicine Publications
 
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Created: Mon, 17 Nov 2014, 11:26:21 EST by Ms Kate Rowe on behalf of School of Chemistry & Molecular Biosciences