Wyszynski, Asaf, Hong, Chi-Chen, Lam, Kristin, Michailidou, Kyriaki ORCID: 0000-0001-7065-1237, Lytle, Christian, Yao, Song ORCID: 0000-0001-9442-1313, Zhang, Yali, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Hopper, John L., Southey, Melissa C., Schmidt, Marjanka K., Broeks, Annegien, Muir, Kenneth, Lophatananon, Artitaya, Fasching, Peter A., Beckmann, Matthias W., Peto, Julian, dos-Santos-Silva, Isabel, Sawyer, Elinor J., Tomlinson, Ian, Burwinkel, Barbara, Marme, Frederik, Guenel, Pascal ORCID: 0000-0002-8359-518X, Truong, Therese, Bojesen, Stig E., Nordestgaard, Borge G., Gonzalez-Neira, Anna ORCID: 0000-0002-5421-2020, Benitez, Javier, Neuhausen, Susan L., Brenner, Hermann, Dieffenbach, Aida Karina, Meindl, Alfons, Schmutzler, Rita K., Brauch, Hiltrud ORCID: 0000-0001-7531-2736, Nevanlinna, Heli, Khan, Sofia ORCID: 0000-0003-4185-8882, Matsuo, Keitaro ORCID: 0000-0003-1761-6314, Ito, Hidemi, Doerk, Thilo, Bogdanova, Natalia V., Lindblom, Annika, Margolin, Sara, Mannermaa, Arto, Kosma, Veli-Matti, Wu, Anna H., Van den Berg, David, Lambrechts, Diether ORCID: 0000-0002-3429-302X, Wildiers, Hans, Chang-Claude, Jenny, Rudolph, Anja, Radice, Paolo ORCID: 0000-0001-6298-4111, Peterlongo, Paolo ORCID: 0000-0001-6951-6855, Couch, Fergus J., Olson, Janet E., Giles, Graham G., Milne, Roger L., Haiman, Christopher A., Henderson, Brian E., Dumont, Martine, Teo, Soo Hwang, Wong, Tien Y., Kristensen, Vessela, Zheng, Wei ORCID: 0000-0003-1226-070X, Long, Jirong ORCID: 0000-0002-7433-9766, Winqvist, Robert, Pylkas, Katri ORCID: 0000-0002-2449-0521, Andrulis, Irene L., Knight, Julia A., Devilee, Peter ORCID: 0000-0002-8023-2009, Seynaeve, Caroline, Garcia-Closas, Montserrat, Figueroa, Jonine, Klevebring, Daniel, Czene, Kamila, Hooning, Maartje J., van den Ouweland, Ans M. W., Darabi, Hatef, Shu, Xiao-Ou, Gao, Yu-Tang, Cox, Angela ORCID: 0000-0002-5138-1099, Blot, William, Signorello, Lisa B., Shah, Mitul, Kang, Daehee, Choi, Ji-Yeob, Hartman, Mikael ORCID: 0000-0001-5726-9965, Miao, Hui, Hamann, Ute, Jakubowska, Anna ORCID: 0000-0002-5650-0501, Lubinski, Jan ORCID: 0000-0003-2931-3003, Sangrajrang, Suleeporn, McKay, James, Toland, Amanda E., Yannoukakos, Drakoulis ORCID: 0000-0001-7509-3510, Shen, Chen-Yang, Wu, Pei-Ei, Swerdlow, Anthony ORCID: 0000-0001-5550-4159, Orr, Nick, Simard, Jacques, Pharoah, Paul D. P., Dunning, Alison M., Chenevix-Trench, Georgia ORCID: 0000-0002-1878-2587, Hall, Per, Bandera, Elisa, Amos, Chris, Ambrosone, Christine, Easton, Douglas F. and Cole, Michael D.
(2016).
An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression.
Hum. Mol. Genet., 25 (17).
S. 3863 - 3877.
OXFORD:
OXFORD UNIV PRESS.
ISSN 1460-2083
Full text not available from this repository.
Abstract
Breast cancer is the most diagnosed malignancy and the second leading cause of cancer mortality in females. Previous association studies have identified variants on 2q35 associated with the risk of breast cancer. To identify functional susceptibility loci for breast cancer, we interrogated the 2q35 gene desert for chromatin architecture and functional variation correlated with gene expression. We report a novel intergenic breast cancer risk locus containing an enhancer copy number variation (enCNV; deletion) located approximately 400Kb upstream to IGFBP5, which overlaps an intergenic ER alpha-bound enhancer that loops to the IGFBP5 promoter. The enCNV is correlated with modified ER alpha binding and monoallelic-repression of IGFBP5 following oestrogen treatment. We investigated the association of enCNV genotype with breast cancer in 1,182 cases and 1,362 controls, and replicate our findings in an independent set of 62,533 cases and 60,966 controls from 41 case control studies and 11 GWAS. We report a dose-dependent inverse association of 2q35 enCNV genotype (percopy OR = 0.68 95% CI 0.55-0.83, P = 0.0002; replication OR = 0.77 95% CI 0.73-0.82, P = 2.1 x 10 (-19)) and identify 13 additional linked variants (r(2) > 0.8) in the 20Kb linkage block containing the enCNV (P = 3.2 x 10 (-15) - 5.6 x 10 (-17)). These associations were independent of previously reported 2q35 variants, rs13387042/rs4442975 and rs16857609, and were stronger for ER-positive than ER-negative disease. Together, these results suggest that 2q35 breast cancer risk loci may be mediating their effect through IGFBP5.
Item Type: |
Journal Article
|
Creators: |
Creators | Email | ORCID | ORCID Put Code |
---|
Wyszynski, Asaf | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Hong, Chi-Chen | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lam, Kristin | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Michailidou, Kyriaki | UNSPECIFIED | orcid.org/0000-0001-7065-1237 | UNSPECIFIED | Lytle, Christian | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Yao, Song | UNSPECIFIED | orcid.org/0000-0001-9442-1313 | UNSPECIFIED | Zhang, Yali | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Bolla, Manjeet K. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wang, Qin | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Dennis, Joe | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Hopper, John L. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Southey, Melissa C. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Schmidt, Marjanka K. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Broeks, Annegien | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Muir, Kenneth | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lophatananon, Artitaya | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Fasching, Peter A. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Beckmann, Matthias W. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Peto, Julian | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | dos-Santos-Silva, Isabel | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Sawyer, Elinor J. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Tomlinson, Ian | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Burwinkel, Barbara | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Marme, Frederik | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Guenel, Pascal | UNSPECIFIED | orcid.org/0000-0002-8359-518X | UNSPECIFIED | Truong, Therese | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Bojesen, Stig E. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Nordestgaard, Borge G. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Gonzalez-Neira, Anna | UNSPECIFIED | orcid.org/0000-0002-5421-2020 | UNSPECIFIED | Benitez, Javier | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Neuhausen, Susan L. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Brenner, Hermann | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Dieffenbach, Aida Karina | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Meindl, Alfons | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Schmutzler, Rita K. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Brauch, Hiltrud | UNSPECIFIED | orcid.org/0000-0001-7531-2736 | UNSPECIFIED | Nevanlinna, Heli | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Khan, Sofia | UNSPECIFIED | orcid.org/0000-0003-4185-8882 | UNSPECIFIED | Matsuo, Keitaro | UNSPECIFIED | orcid.org/0000-0003-1761-6314 | UNSPECIFIED | Ito, Hidemi | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Doerk, Thilo | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Bogdanova, Natalia V. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lindblom, Annika | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Margolin, Sara | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Mannermaa, Arto | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Kosma, Veli-Matti | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wu, Anna H. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Van den Berg, David | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lambrechts, Diether | UNSPECIFIED | orcid.org/0000-0002-3429-302X | UNSPECIFIED | Wildiers, Hans | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Chang-Claude, Jenny | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Rudolph, Anja | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Radice, Paolo | UNSPECIFIED | orcid.org/0000-0001-6298-4111 | UNSPECIFIED | Peterlongo, Paolo | UNSPECIFIED | orcid.org/0000-0001-6951-6855 | UNSPECIFIED | Couch, Fergus J. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Olson, Janet E. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Giles, Graham G. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Milne, Roger L. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Haiman, Christopher A. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Henderson, Brian E. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Dumont, Martine | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Teo, Soo Hwang | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wong, Tien Y. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Kristensen, Vessela | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Zheng, Wei | UNSPECIFIED | orcid.org/0000-0003-1226-070X | UNSPECIFIED | Long, Jirong | UNSPECIFIED | orcid.org/0000-0002-7433-9766 | UNSPECIFIED | Winqvist, Robert | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Pylkas, Katri | UNSPECIFIED | orcid.org/0000-0002-2449-0521 | UNSPECIFIED | Andrulis, Irene L. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Knight, Julia A. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Devilee, Peter | UNSPECIFIED | orcid.org/0000-0002-8023-2009 | UNSPECIFIED | Seynaeve, Caroline | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Garcia-Closas, Montserrat | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Figueroa, Jonine | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Klevebring, Daniel | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Czene, Kamila | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Hooning, Maartje J. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | van den Ouweland, Ans M. W. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Darabi, Hatef | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Shu, Xiao-Ou | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Gao, Yu-Tang | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Cox, Angela | UNSPECIFIED | orcid.org/0000-0002-5138-1099 | UNSPECIFIED | Blot, William | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Signorello, Lisa B. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Shah, Mitul | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Kang, Daehee | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Choi, Ji-Yeob | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Hartman, Mikael | UNSPECIFIED | orcid.org/0000-0001-5726-9965 | UNSPECIFIED | Miao, Hui | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Hamann, Ute | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Jakubowska, Anna | UNSPECIFIED | orcid.org/0000-0002-5650-0501 | UNSPECIFIED | Lubinski, Jan | UNSPECIFIED | orcid.org/0000-0003-2931-3003 | UNSPECIFIED | Sangrajrang, Suleeporn | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | McKay, James | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Toland, Amanda E. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Yannoukakos, Drakoulis | UNSPECIFIED | orcid.org/0000-0001-7509-3510 | UNSPECIFIED | Shen, Chen-Yang | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wu, Pei-Ei | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Swerdlow, Anthony | UNSPECIFIED | orcid.org/0000-0001-5550-4159 | UNSPECIFIED | Orr, Nick | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Simard, Jacques | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Pharoah, Paul D. P. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Dunning, Alison M. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Chenevix-Trench, Georgia | UNSPECIFIED | orcid.org/0000-0002-1878-2587 | UNSPECIFIED | Hall, Per | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Bandera, Elisa | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Amos, Chris | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Ambrosone, Christine | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Easton, Douglas F. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Cole, Michael D. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
|
URN: |
urn:nbn:de:hbz:38-265616 |
DOI: |
10.1093/hmg/ddw223 |
Journal or Publication Title: |
Hum. Mol. Genet. |
Volume: |
25 |
Number: |
17 |
Page Range: |
S. 3863 - 3877 |
Date: |
2016 |
Publisher: |
OXFORD UNIV PRESS |
Place of Publication: |
OXFORD |
ISSN: |
1460-2083 |
Language: |
English |
Faculty: |
Unspecified |
Divisions: |
Unspecified |
Subjects: |
no entry |
Uncontrolled Keywords: |
Keywords | Language |
---|
GENOME-WIDE ASSOCIATION; GENOTYPE IMPUTATION; GROWTH; SUSCEPTIBILITY; ACTIVATION; INVOLUTION; MUTATION; CELLS | Multiple languages | Biochemistry & Molecular Biology; Genetics & Heredity | Multiple languages |
|
Refereed: |
Yes |
URI: |
http://kups.ub.uni-koeln.de/id/eprint/26561 |
Downloads per month over past year
Export