Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.
Loading...
Embargo End Date
ICR Authors
Authors
Dunning, AM
Michailidou, K
Kuchenbaecker, KB
Thompson, D
French, JD
Beesley, J
Healey, CS
Kar, S
Pooley, KA
Lopez-Knowles, E
Dicks, E
Barrowdale, D
Sinnott-Armstrong, NA
Sallari, RC
Hillman, KM
Kaufmann, S
Sivakumaran, H
Moradi Marjaneh, M
Lee, JS
Hills, M
Jarosz, M
Drury, S
Canisius, S
Bolla, MK
Dennis, J
Wang, Q
Hopper, JL
Southey, MC
Broeks, A
Schmidt, MK
Lophatananon, A
Muir, K
Beckmann, MW
Fasching, PA
Dos-Santos-Silva, I
Peto, J
Sawyer, EJ
Tomlinson, I
Burwinkel, B
Marme, F
Guénel, P
Truong, T
Bojesen, SE
Flyger, H
González-Neira, A
Perez, JIA
Anton-Culver, H
Eunjung, L
Arndt, V
Brenner, H
Meindl, A
Schmutzler, RK
Brauch, H
Hamann, U
Aittomäki, K
Blomqvist, C
Ito, H
Matsuo, K
Bogdanova, N
Dörk, T
Lindblom, A
Margolin, S
Kosma, V-M
Mannermaa, A
Tseng, C-C
Wu, AH
Lambrechts, D
Wildiers, H
Chang-Claude, J
Rudolph, A
Peterlongo, P
Radice, P
Olson, JE
Giles, GG
Milne, RL
Haiman, CA
Henderson, BE
Goldberg, MS
Teo, SH
Yip, CH
Nord, S
Borresen-Dale, A-L
Kristensen, V
Long, J
Zheng, W
Pylkäs, K
Winqvist, R
Andrulis, IL
Knight, JA
Devilee, P
Seynaeve, C
Figueroa, J
Sherman, ME
Czene, K
Darabi, H
Hollestelle, A
van den Ouweland, AMW
Humphreys, K
Gao, Y-T
Shu, X-O
Cox, A
Cross, SS
Blot, W
Cai, Q
Ghoussaini, M
Perkins, BJ
Shah, M
Choi, J-Y
Kang, D
Lee, SC
Hartman, M
Kabisch, M
Torres, D
Jakubowska, A
Lubinski, J
Brennan, P
Sangrajrang, S
Ambrosone, CB
Toland, AE
Shen, C-Y
Wu, P-E
Orr, N
Swerdlow, A
McGuffog, L
Healey, S
Lee, A
Kapuscinski, M
John, EM
Terry, MB
Daly, MB
Goldgar, DE
Buys, SS
Janavicius, R
Tihomirova, L
Tung, N
Dorfling, CM
van Rensburg, EJ
Neuhausen, SL
Ejlertsen, B
Hansen, TVO
Osorio, A
Benitez, J
Rando, R
Weitzel, JN
Bonanni, B
Peissel, B
Manoukian, S
Papi, L
Ottini, L
Konstantopoulou, I
Apostolou, P
Garber, J
Rashid, MU
Frost, D
EMBRACE,
Izatt, L
Ellis, S
Godwin, AK
Arnold, N
Niederacher, D
Rhiem, K
Bogdanova-Markov, N
Sagne, C
Stoppa-Lyonnet, D
Damiola, F
GEMO Study Collaborators,
Sinilnikova, OM
Mazoyer, S
Isaacs, C
Claes, KBM
De Leeneer, K
de la Hoya, M
Caldes, T
Nevanlinna, H
Khan, S
Mensenkamp, AR
HEBON,
Hooning, MJ
Rookus, MA
Kwong, A
Olah, E
Diez, O
Brunet, J
Pujana, MA
Gronwald, J
Huzarski, T
Barkardottir, RB
Laframboise, R
Soucy, P
Montagna, M
Agata, S
Teixeira, MR
kConFab Investigators,
Park, SK
Lindor, N
Couch, FJ
Tischkowitz, M
Foretova, L
Vijai, J
Offit, K
Singer, CF
Rappaport, C
Phelan, CM
Greene, MH
Mai, PL
Rennert, G
Imyanitov, EN
Hulick, PJ
Phillips, K-A
Piedmonte, M
Mulligan, AM
Glendon, G
Bojesen, A
Thomassen, M
Caligo, MA
Yoon, S-Y
Friedman, E
Laitman, Y
Borg, A
von Wachenfeldt, A
Ehrencrona, H
Rantala, J
Olopade, OI
Ganz, PA
Nussbaum, RL
Gayther, SA
Nathanson, KL
Domchek, SM
Arun, BK
Mitchell, G
Karlan, BY
Lester, J
Maskarinec, G
Woolcott, C
Scott, C
Stone, J
Apicella, C
Tamimi, R
Luben, R
Khaw, K-T
Helland, Å
Haakensen, V
Dowsett, M
Pharoah, PDP
Simard, J
Hall, P
García-Closas, M
Vachon, C
Chenevix-Trench, G
Antoniou, AC
Easton, DF
Edwards, SL
Michailidou, K
Kuchenbaecker, KB
Thompson, D
French, JD
Beesley, J
Healey, CS
Kar, S
Pooley, KA
Lopez-Knowles, E
Dicks, E
Barrowdale, D
Sinnott-Armstrong, NA
Sallari, RC
Hillman, KM
Kaufmann, S
Sivakumaran, H
Moradi Marjaneh, M
Lee, JS
Hills, M
Jarosz, M
Drury, S
Canisius, S
Bolla, MK
Dennis, J
Wang, Q
Hopper, JL
Southey, MC
Broeks, A
Schmidt, MK
Lophatananon, A
Muir, K
Beckmann, MW
Fasching, PA
Dos-Santos-Silva, I
Peto, J
Sawyer, EJ
Tomlinson, I
Burwinkel, B
Marme, F
Guénel, P
Truong, T
Bojesen, SE
Flyger, H
González-Neira, A
Perez, JIA
Anton-Culver, H
Eunjung, L
Arndt, V
Brenner, H
Meindl, A
Schmutzler, RK
Brauch, H
Hamann, U
Aittomäki, K
Blomqvist, C
Ito, H
Matsuo, K
Bogdanova, N
Dörk, T
Lindblom, A
Margolin, S
Kosma, V-M
Mannermaa, A
Tseng, C-C
Wu, AH
Lambrechts, D
Wildiers, H
Chang-Claude, J
Rudolph, A
Peterlongo, P
Radice, P
Olson, JE
Giles, GG
Milne, RL
Haiman, CA
Henderson, BE
Goldberg, MS
Teo, SH
Yip, CH
Nord, S
Borresen-Dale, A-L
Kristensen, V
Long, J
Zheng, W
Pylkäs, K
Winqvist, R
Andrulis, IL
Knight, JA
Devilee, P
Seynaeve, C
Figueroa, J
Sherman, ME
Czene, K
Darabi, H
Hollestelle, A
van den Ouweland, AMW
Humphreys, K
Gao, Y-T
Shu, X-O
Cox, A
Cross, SS
Blot, W
Cai, Q
Ghoussaini, M
Perkins, BJ
Shah, M
Choi, J-Y
Kang, D
Lee, SC
Hartman, M
Kabisch, M
Torres, D
Jakubowska, A
Lubinski, J
Brennan, P
Sangrajrang, S
Ambrosone, CB
Toland, AE
Shen, C-Y
Wu, P-E
Orr, N
Swerdlow, A
McGuffog, L
Healey, S
Lee, A
Kapuscinski, M
John, EM
Terry, MB
Daly, MB
Goldgar, DE
Buys, SS
Janavicius, R
Tihomirova, L
Tung, N
Dorfling, CM
van Rensburg, EJ
Neuhausen, SL
Ejlertsen, B
Hansen, TVO
Osorio, A
Benitez, J
Rando, R
Weitzel, JN
Bonanni, B
Peissel, B
Manoukian, S
Papi, L
Ottini, L
Konstantopoulou, I
Apostolou, P
Garber, J
Rashid, MU
Frost, D
EMBRACE,
Izatt, L
Ellis, S
Godwin, AK
Arnold, N
Niederacher, D
Rhiem, K
Bogdanova-Markov, N
Sagne, C
Stoppa-Lyonnet, D
Damiola, F
GEMO Study Collaborators,
Sinilnikova, OM
Mazoyer, S
Isaacs, C
Claes, KBM
De Leeneer, K
de la Hoya, M
Caldes, T
Nevanlinna, H
Khan, S
Mensenkamp, AR
HEBON,
Hooning, MJ
Rookus, MA
Kwong, A
Olah, E
Diez, O
Brunet, J
Pujana, MA
Gronwald, J
Huzarski, T
Barkardottir, RB
Laframboise, R
Soucy, P
Montagna, M
Agata, S
Teixeira, MR
kConFab Investigators,
Park, SK
Lindor, N
Couch, FJ
Tischkowitz, M
Foretova, L
Vijai, J
Offit, K
Singer, CF
Rappaport, C
Phelan, CM
Greene, MH
Mai, PL
Rennert, G
Imyanitov, EN
Hulick, PJ
Phillips, K-A
Piedmonte, M
Mulligan, AM
Glendon, G
Bojesen, A
Thomassen, M
Caligo, MA
Yoon, S-Y
Friedman, E
Laitman, Y
Borg, A
von Wachenfeldt, A
Ehrencrona, H
Rantala, J
Olopade, OI
Ganz, PA
Nussbaum, RL
Gayther, SA
Nathanson, KL
Domchek, SM
Arun, BK
Mitchell, G
Karlan, BY
Lester, J
Maskarinec, G
Woolcott, C
Scott, C
Stone, J
Apicella, C
Tamimi, R
Luben, R
Khaw, K-T
Helland, Å
Haakensen, V
Dowsett, M
Pharoah, PDP
Simard, J
Hall, P
García-Closas, M
Vachon, C
Chenevix-Trench, G
Antoniou, AC
Easton, DF
Edwards, SL
Document Type
Journal Article
Date
2016-04-01
Date Accepted
2016-02-05
Abstract
We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.
Citation
Nature genetics, 2016, 48 (4), pp. 374 - 386
DOI
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
1061-4036
eISSN
1546-1718
Research Team
Complex Trait Genetics
Aetiological Epidemiology
Endocrinology
Aetiological Epidemiology
Endocrinology