Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.
Dunning, AM; Michailidou, K; Kuchenbaecker, KB; Thompson, D; French, JD; Beesley, J; Healey, CS; Kar, S; Pooley, KA; Lopez-Knowles, E; +242 more...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, JI; 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; Mannermaa, A; Tseng, 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; 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, AM; Humphreys, K; Gao, Y; Shu, X; Cox, A; Cross, SS; Blot, W; Cai, Q; Ghoussaini, M; Perkins, BJ; Shah, M; Choi, J; Kang, D; Lee, SC; Hartman, M; Kabisch, M; Torres, D; Jakubowska, A; Lubinski, J; Brennan, P; Sangrajrang, S; Ambrosone, CB; Toland, AE; Shen, C; Wu, P; 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, TV; 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, KB; 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; Piedmonte, M; Mulligan, AM; Glendon, G; Bojesen, A; Thomassen, M; Caligo, MA; Yoon, S; 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; Helland, Å; Haakensen, V; Dowsett, M; Pharoah, PD; Simard, J; Hall, P; García-Closas, M; Vachon, C; Chenevix-Trench, G; Antoniou, AC; Easton, DF; Edwards, SL and
(2016)
Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.
Nature genetics, 48 (4).
pp. 374-386.
ISSN 1061-4036
DOI: 10.1038/ng.3521
; Peto, J; Sawyer, EJ; Tomlinson, I; Burwinkel, B; Marme, F; Guénel, P; Truong, T; Bojesen, SE; Flyger, H; González-Neira, A; Perez, JI; 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; Mannermaa, A; Tseng, 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; 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, AM; Humphreys, K; Gao, Y; Shu, X; Cox, A; Cross, SS; Blot, W; Cai, Q; Ghoussaini, M; Perkins, BJ; Shah, M; Choi, J; Kang, D; Lee, SC; Hartman, M; Kabisch, M; Torres, D; Jakubowska, A; Lubinski, J; Brennan, P; Sangrajrang, S; Ambrosone, CB; Toland, AE; Shen, C; Wu, P; 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, TV; 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, KB; 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; Piedmonte, M; Mulligan, AM; Glendon, G; Bojesen, A; Thomassen, M; Caligo, MA; Yoon, S; 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; Helland, Å; Haakensen, V; Dowsett, M; Pharoah, PD; Simard, J; Hall, P; García-Closas, M; Vachon, C; Chenevix-Trench, G; Antoniou, AC; Easton, DF; Edwards, SL and
(2016)
Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.
Nature genetics, 48 (4).
pp. 374-386.
ISSN 1061-4036
DOI: 10.1038/ng.3521
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.
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picture_as_pdf - NG-A39955R3_ESR1 final manuscript.pdf
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subject - Accepted Version
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- Available under Creative Commons: Attribution-NonCommercial-No Derivative Works 3.0
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