Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170

Alison M. Dunning; Kyriaki Michailidou; Karoline B. Kuchenbaecker; Deborah Thompson; Juliet D. French; Jonathan Beesley; Catherine S. Healey; Siddhartha Kar; Karen A. Pooley; Elena Lopez-Knowles; Ed Dicks; Daniel Barrowdale; Nicholas A. Sinnott-Armstrong; Richard C. Sallari; Kristine M. Hillman; Susanne Kaufmann; Haran Sivakumaran; Mahdi Moradi Marjaneh; Jason S. Lee; Margaret Hills; Monika Jarosz; Suzie Drury; Sander Canisius; Manjeet KBolla; Joe Dennis; Qin Wang; John LHopper; Melissa C. Southey; Annegien Broeks; Marjanka K. Schmidt; Artitaya Lophatananon; Kenneth Muir; Matthias W. Beckmann; Peter A. Fasching; Isabel Dos-Santos-Silva; Julian Peto; Elinor J. Sawyer; Ian Tomlinson; Barbara Burwinkel; Frederik Marme; Pascal Guénel; Thérse Truong; Stig E. Bojesen; Henrik Flyger; Anna Gonzlez-Neira; Jose I.A. Perez; Hoda Anton-Culver; Lee Eunjung; Volker Arndt; Hermann Brenner; Alfons Meindl; Rita K. Schmutzler; Hiltrud Brauch; Ute Hamann; Kristiina Aittomki; Carl Blomqvist; Hidemi Ito; Keitaro Matsuo; Natasha Bogdanova; Thilo Dörk; Annika Lindblom; Sara Margolin; Veli Matti Kosma; Arto Mannermaa; Chiu Chen Tseng; Anna H. Wu; Diether Lambrechts; Hans Wildiers; Jenny Chang-Claude; Anja Rudolph; Paolo Peterlongo; Paolo Radice; Janet EOlson; Graham GGiles; Roger L. Milne; Christopher A. Haiman; Brian E. Henderson; Mark S. Goldberg; Soo H. Teo; Cheng Har Yip; Silje Nord; Anne Lise Borresen-Dale; Vessela Kristensen; Jirong Long; Wei Zheng; Katri Pylks; Robert Winqvist; Irene L. Andrulis; Julia A. Knight; Peter Devilee; Caroline Seynaeve; Jonine Figueroa; Mark E. Sherman; Kamila Czene; Hatef Darabi; Antoinette Hollestelle; Ans M.W. Van Den Ouweland; Keith Humphreys; Yu Tang Gao; Xiao Ou Shu; Angela Cox; Simon S. Cross; William Blot; Qiuyin Cai; Maya Ghoussaini; Barbara J. Perkins; Mitul Shah; Ji Yeob Choi; Daehee Kang; Soo Chin Lee; Mikael Hartman; Maria Kabisch; Diana Torres; Anna Jakubowska; Jan Lubinski; Paul Brennan; Suleeporn Sangrajrang; Christine B. Ambrosone; Amanda E. Toland; Chen Yang Shen; Pei Ei Wu; Nick Orr; Anthony Swerdlow; Lesley McGuffog; Sue Healey; Andrew Lee; Miroslav Kapuscinski; Esther M. John; Mary Beth Terry; Mary B. Daly; David E. Goldgar; Saundra S. Buys; Ramunas Janavicius; Laima Tihomirova; Nadine Tung; Cecilia M. Dorfling; Elizabeth J. Van Rensburg; Susan L. Neuhausen; Bent Ejlertsen; Thomas V. OHansen; Ana Osorio; Javier Benitez; Rachel Rando; Jeffrey N. Weitzel; Bernardo Bonanni; Bernard Peissel; Siranoush Manoukian; Laura Papi; Laura Ottini; Irene Konstantopoulou; Paraskevi Apostolou; Judy Garber; Muhammad Usman Rashid; Debra Frost; Louise Izatt; Steve Ellis; Andrew K. Godwin; Norbert Arnold; Dieter Niederacher; Kerstin Rhiem; Nadja Bogdanova-Markov; Charlotte Sagne; Dominique Stoppa-Lyonnet; Francesca Damiola; Olga M. Sinilnikova; Sylvie Mazoyer; Claudine Isaacs; Kathleen B. MClaes; Kim De Leeneer; Miguel De La Hoya; Trinidad Caldes; Heli Nevanlinna; Sofia Khan; Arjen R. Mensenkamp; Maartje J. Hooning; Matti A. Rookus; Ava Kwong; Edith Olah; Orland Diez; Joan Brunet; Miquel Angel Pujana; Jacek Gronwald; Tomasz Huzarski; Rosa B. Barkardottir; Rachel Laframboise; Penny Soucy; Marco Montagna; Simona Agata; Manuel R. Teixeira; Sue Kyung Park; Noralane Lindor; Fergus J. Couch; Marc Tischkowitz; Lenka Foretova; Joseph Vijai; Kenneth Offit; Christian F. Singer; Christine Rappaport; Catherine MPhelan; Mark H. Greene; Phuong L. Mai; Gad Rennert; Evgeny N. Imyanitov; Peter J. Hulick; Kelly Anne Phillips; Marion Piedmonte; Anna Marie Mulligan; Gord Glendon; Anders Bojesen; Mads Thomassen; Maria A. Caligo; Sook Yee Yoon; Eitan Friedman; Yael Laitman; Ake Borg; Anna Von Wachenfeldt; Hans Ehrencrona; Johanna Rantala; Olufunmilayo I. Olopade; Patricia A. Ganz; Robert L. Nussbaum; Simon A. Gayther; Katherine LNathanson; Susan M. Domchek; Banu K. Arun; Gillian Mitchell; Beth Y. Karlan; Jenny Lester; Gertraud Maskarinec; Christy Woolcott; Christopher Scott; Jennifer Stone; Carmel Apicella; Rulla Tamimi; Robert Luben; Kay Tee Khaw; Slaug Helland; Vilde Haakensen; Mitch Dowsett; Paul D.P. Pharoah; Jacques Simard; Per Hall; Montserrat Garca-Closas; Celine Vachon; Georgia Chenevix-Trench; Antonis C. Antoniou; Douglas F. Easton; Stacey L. Edwards

doi:10.1038/ng.3521

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170

Alison M. Dunning, Kyriaki Michailidou, Karoline B. Kuchenbaecker, Deborah Thompson, Juliet D. French, Jonathan Beesley, Catherine S. Healey, Siddhartha Kar, Karen A. Pooley, Elena Lopez-Knowles, Ed Dicks, Daniel Barrowdale, Nicholas A. Sinnott-Armstrong, Richard C. Sallari, Kristine M. Hillman, Susanne Kaufmann, Haran Sivakumaran, Mahdi Moradi Marjaneh, Jason S. Lee, Margaret HillsMonika Jarosz, Suzie Drury, Sander Canisius, Manjeet KBolla, Joe Dennis, Qin Wang, John LHopper, Melissa C. Southey, Annegien Broeks, Marjanka K. Schmidt, Artitaya Lophatananon, Kenneth Muir, Matthias W. Beckmann, Peter A. Fasching, Isabel Dos-Santos-Silva, Julian Peto, Elinor J. Sawyer, Ian Tomlinson, Barbara Burwinkel, Frederik Marme, Pascal Guénel, Thérse Truong, Stig E. Bojesen, Henrik Flyger, Anna Gonzlez-Neira, Jose I.A. Perez, Hoda Anton-Culver, Lee Eunjung, Volker Arndt, Hermann Brenner, Alfons Meindl, Rita K. Schmutzler, Hiltrud Brauch, Ute Hamann, Kristiina Aittomki, Carl Blomqvist, Hidemi Ito, Keitaro Matsuo, Natasha Bogdanova, Thilo Dörk, Annika Lindblom, Sara Margolin, Veli Matti Kosma, Arto Mannermaa, Chiu Chen Tseng, Anna H. Wu, Diether Lambrechts, Hans Wildiers, Jenny Chang-Claude, Anja Rudolph, Paolo Peterlongo, Paolo Radice, Janet EOlson, Graham GGiles, Roger L. Milne, Christopher A. Haiman, Brian E. Henderson, Mark S. Goldberg, Soo H. Teo, Cheng Har Yip, Silje Nord, Anne Lise Borresen-Dale, Vessela Kristensen, Jirong Long, Wei Zheng, Katri Pylks, Robert Winqvist, Irene L. Andrulis, Julia A. Knight, Peter Devilee, Caroline Seynaeve, Jonine Figueroa, Mark E. Sherman, Kamila Czene, Hatef Darabi, Antoinette Hollestelle, Ans M.W. Van Den Ouweland, Keith Humphreys, Yu Tang Gao, Xiao Ou Shu, Angela Cox, Simon S. Cross, William Blot, Qiuyin Cai, Maya Ghoussaini, Barbara J. Perkins, Mitul Shah, Ji Yeob Choi, Daehee Kang, Soo Chin Lee, Mikael Hartman, Maria Kabisch, Diana Torres, Anna Jakubowska, Jan Lubinski, Paul Brennan, Suleeporn Sangrajrang, Christine B. Ambrosone, Amanda E. Toland, Chen Yang Shen, Pei Ei Wu, Nick Orr, Anthony Swerdlow, Lesley McGuffog, Sue Healey, Andrew Lee, Miroslav Kapuscinski, Esther M. John, Mary Beth Terry, Mary B. Daly, David E. Goldgar, Saundra S. Buys, Ramunas Janavicius, Laima Tihomirova, Nadine Tung, Cecilia M. Dorfling, Elizabeth J. Van Rensburg, Susan L. Neuhausen, Bent Ejlertsen, Thomas V. OHansen, Ana Osorio, Javier Benitez, Rachel Rando, Jeffrey N. Weitzel, Bernardo Bonanni, Bernard Peissel, Siranoush Manoukian, Laura Papi, Laura Ottini, Irene Konstantopoulou, Paraskevi Apostolou, Judy Garber, Muhammad Usman Rashid, Debra Frost, Louise Izatt, Steve Ellis, Andrew K. Godwin, Norbert Arnold, Dieter Niederacher, Kerstin Rhiem, Nadja Bogdanova-Markov, Charlotte Sagne, Dominique Stoppa-Lyonnet, Francesca Damiola, Olga M. Sinilnikova, Sylvie Mazoyer, Claudine Isaacs, Kathleen B. MClaes, Kim De Leeneer, Miguel De La Hoya, Trinidad Caldes, Heli Nevanlinna, Sofia Khan, Arjen R. Mensenkamp, Maartje J. Hooning, Matti A. Rookus, Ava Kwong, Edith Olah, Orland Diez, Joan Brunet, Miquel Angel Pujana, Jacek Gronwald, Tomasz Huzarski, Rosa B. Barkardottir, Rachel Laframboise, Penny Soucy, Marco Montagna, Simona Agata, Manuel R. Teixeira, Sue Kyung Park, Noralane Lindor, Fergus J. Couch, Marc Tischkowitz, Lenka Foretova, Joseph Vijai, Kenneth Offit, Christian F. Singer, Christine Rappaport, Catherine MPhelan, Mark H. Greene, Phuong L. Mai, Gad Rennert, Evgeny N. Imyanitov, Peter J. Hulick, Kelly Anne Phillips, Marion Piedmonte, Anna Marie Mulligan, Gord Glendon, Anders Bojesen, Mads Thomassen, Maria A. Caligo, Sook Yee Yoon, Eitan Friedman, Yael Laitman, Ake Borg, Anna Von Wachenfeldt, Hans Ehrencrona, Johanna Rantala, Olufunmilayo I. Olopade, Patricia A. Ganz, Robert L. Nussbaum, Simon A. Gayther, Katherine LNathanson, Susan M. Domchek, Banu K. Arun, Gillian Mitchell, Beth Y. Karlan, Jenny Lester, Gertraud Maskarinec, Christy Woolcott, Christopher Scott, Jennifer Stone, Carmel Apicella, Rulla Tamimi, Robert Luben, Kay Tee Khaw, Slaug Helland, Vilde Haakensen, Mitch Dowsett, Paul D.P. Pharoah, Jacques Simard, Per Hall, Montserrat Garca-Closas, Celine Vachon, Georgia Chenevix-Trench, Antonis C. Antoniou, Douglas F. Easton, Stacey L. Edwards

Research output: Contribution to journal › Article › peer-review

70 Scopus citations

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.

Original language	English (US)
Pages (from-to)	374-386
Number of pages	13
Journal	Nature Genetics
Volume	48
Issue number	4
DOIs	https://doi.org/10.1038/ng.3521
State	Published - Mar 29 2016

ASJC Scopus subject areas

Genetics

Access to Document

10.1038/ng.3521

Cite this

Dunning, A. M., Michailidou, K., Kuchenbaecker, K. B., Thompson, D., French, J. D., Beesley, J., Healey, C. S., Kar, S., Pooley, K. A., Lopez-Knowles, E., Dicks, E., Barrowdale, D., Sinnott-Armstrong, N. A., Sallari, R. C., Hillman, K. M., Kaufmann, S., Sivakumaran, H., Marjaneh, M. M., Lee, J. S., ... Edwards, S. L. (2016). Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170. Nature Genetics, 48(4), 374-386. https://doi.org/10.1038/ng.3521

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, Marjaneh, MM, Lee, JS, Hills, M, Jarosz, M, Drury, S, Canisius, S, KBolla, M, Dennis, J, Wang, Q, LHopper, J, 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, Gonzlez-Neira, A, Perez, JIA, Anton-Culver, H, Eunjung, L, Arndt, V, Brenner, H, Meindl, A, Schmutzler, RK, Brauch, H, Hamann, U, Aittomki, K, Blomqvist, C, Ito, H, Matsuo, K, Bogdanova, N, Dörk, T, Lindblom, A, Margolin, S, Kosma, VM, Mannermaa, A, Tseng, CC, Wu, AH, Lambrechts, D, Wildiers, H, Chang-Claude, J, Rudolph, A, Peterlongo, P, Radice, P, EOlson, J, GGiles, G, Milne, RL, Haiman, CA, Henderson, BE, Goldberg, MS, Teo, SH, Yip, CH, Nord, S, Borresen-Dale, AL, Kristensen, V, Long, J, Zheng, W, Pylks, 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, YT, Shu, XO, Cox, A, Cross, SS, Blot, W, Cai, Q, Ghoussaini, M, Perkins, BJ, Shah, M, Choi, JY, Kang, D, Lee, SC, Hartman, M, Kabisch, M, Torres, D, Jakubowska, A, Lubinski, J, Brennan, P, Sangrajrang, S, Ambrosone, CB, Toland, AE, Shen, CY, Wu, PE, 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, OHansen, 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, Izatt, L, Ellis, S, Godwin, AK, Arnold, N, Niederacher, D, Rhiem, K, Bogdanova-Markov, N, Sagne, C, Stoppa-Lyonnet, D, Damiola, F, Sinilnikova, OM, Mazoyer, S, Isaacs, C, MClaes, KB, De Leeneer, K, De La Hoya, M, Caldes, T, Nevanlinna, H, Khan, S, Mensenkamp, AR, 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, Kyung Park, S, Lindor, N, Couch, FJ, Tischkowitz, M, Foretova, L, Vijai, J, Offit, K, Singer, CF, Rappaport, C, MPhelan, C, Greene, MH, Mai, PL, Rennert, G, Imyanitov, EN, Hulick, PJ, Phillips, KA, Piedmonte, M, Mulligan, AM, Glendon, G, Bojesen, A, Thomassen, M, Caligo, MA, Yoon, SY, Friedman, E, Laitman, Y, Borg, A, Von Wachenfeldt, A, Ehrencrona, H, Rantala, J, Olopade, OI, Ganz, PA, Nussbaum, RL, Gayther, SA, LNathanson, K, 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, KT, Helland, S, Haakensen, V, Dowsett, M, Pharoah, PDP, Simard, J, Hall, P, Garca-Closas, M, Vachon, C, Chenevix-Trench, G, Antoniou, AC, Easton, DF & Edwards, SL 2016, 'Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170', Nature Genetics, vol. 48, no. 4, pp. 374-386. https://doi.org/10.1038/ng.3521

@article{39c21889902b4016841f6baa5c0d275f,

title = "Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170",

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.",

author = "Dunning, {Alison M.} and Kyriaki Michailidou and Kuchenbaecker, {Karoline B.} and Deborah Thompson and French, {Juliet D.} and Jonathan Beesley and Healey, {Catherine S.} and Siddhartha Kar and Pooley, {Karen A.} and Elena Lopez-Knowles and Ed Dicks and Daniel Barrowdale and Sinnott-Armstrong, {Nicholas A.} and Sallari, {Richard C.} and Hillman, {Kristine M.} and Susanne Kaufmann and Haran Sivakumaran and Marjaneh, {Mahdi Moradi} and Lee, {Jason S.} and Margaret Hills and Monika Jarosz and Suzie Drury and Sander Canisius and Manjeet KBolla and Joe Dennis and Qin Wang and John LHopper and Southey, {Melissa C.} and Annegien Broeks and Schmidt, {Marjanka K.} and Artitaya Lophatananon and Kenneth Muir and Beckmann, {Matthias W.} and Fasching, {Peter A.} and Isabel Dos-Santos-Silva and Julian Peto and Sawyer, {Elinor J.} and Ian Tomlinson and Barbara Burwinkel and Frederik Marme and Pascal Gu{\'e}nel and Th{\'e}rse Truong and Bojesen, {Stig E.} and Henrik Flyger and Anna Gonzlez-Neira and Perez, {Jose I.A.} and Hoda Anton-Culver and Lee Eunjung and Volker Arndt and Hermann Brenner and Alfons Meindl and Schmutzler, {Rita K.} and Hiltrud Brauch and Ute Hamann and Kristiina Aittomki and Carl Blomqvist and Hidemi Ito and Keitaro Matsuo and Natasha Bogdanova and Thilo D{\"o}rk and Annika Lindblom and Sara Margolin and Kosma, {Veli Matti} and Arto Mannermaa and Tseng, {Chiu Chen} and Wu, {Anna H.} and Diether Lambrechts and Hans Wildiers and Jenny Chang-Claude and Anja Rudolph and Paolo Peterlongo and Paolo Radice and Janet EOlson and Graham GGiles and Milne, {Roger L.} and Haiman, {Christopher A.} and Henderson, {Brian E.} and Goldberg, {Mark S.} and Teo, {Soo H.} and Yip, {Cheng Har} and Silje Nord and Borresen-Dale, {Anne Lise} and Vessela Kristensen and Jirong Long and Wei Zheng and Katri Pylks and Robert Winqvist and Andrulis, {Irene L.} and Knight, {Julia A.} and Peter Devilee and Caroline Seynaeve and Jonine Figueroa and Sherman, {Mark E.} and Kamila Czene and Hatef Darabi and Antoinette Hollestelle and {Van Den Ouweland}, {Ans M.W.} and Keith Humphreys and Gao, {Yu Tang} and Shu, {Xiao Ou} and Angela Cox and Cross, {Simon S.} and William Blot and Qiuyin Cai and Maya Ghoussaini and Perkins, {Barbara J.} and Mitul Shah and Choi, {Ji Yeob} and Daehee Kang and Lee, {Soo Chin} and Mikael Hartman and Maria Kabisch and Diana Torres and Anna Jakubowska and Jan Lubinski and Paul Brennan and Suleeporn Sangrajrang and Ambrosone, {Christine B.} and Toland, {Amanda E.} and Shen, {Chen Yang} and Wu, {Pei Ei} and Nick Orr and Anthony Swerdlow and Lesley McGuffog and Sue Healey and Andrew Lee and Miroslav Kapuscinski and John, {Esther M.} and Terry, {Mary Beth} and Daly, {Mary B.} and Goldgar, {David E.} and Buys, {Saundra S.} and Ramunas Janavicius and Laima Tihomirova and Nadine Tung and Dorfling, {Cecilia M.} and {Van Rensburg}, {Elizabeth J.} and Neuhausen, {Susan L.} and Bent Ejlertsen and OHansen, {Thomas V.} and Ana Osorio and Javier Benitez and Rachel Rando and Weitzel, {Jeffrey N.} and Bernardo Bonanni and Bernard Peissel and Siranoush Manoukian and Laura Papi and Laura Ottini and Irene Konstantopoulou and Paraskevi Apostolou and Judy Garber and Rashid, {Muhammad Usman} and Debra Frost and Louise Izatt and Steve Ellis and Godwin, {Andrew K.} and Norbert Arnold and Dieter Niederacher and Kerstin Rhiem and Nadja Bogdanova-Markov and Charlotte Sagne and Dominique Stoppa-Lyonnet and Francesca Damiola and Sinilnikova, {Olga M.} and Sylvie Mazoyer and Claudine Isaacs and MClaes, {Kathleen B.} and {De Leeneer}, Kim and {De La Hoya}, Miguel and Trinidad Caldes and Heli Nevanlinna and Sofia Khan and Mensenkamp, {Arjen R.} and Hooning, {Maartje J.} and Rookus, {Matti A.} and Ava Kwong and Edith Olah and Orland Diez and Joan Brunet and Pujana, {Miquel Angel} and Jacek Gronwald and Tomasz Huzarski and Barkardottir, {Rosa B.} and Rachel Laframboise and Penny Soucy and Marco Montagna and Simona Agata and Teixeira, {Manuel R.} and {Kyung Park}, Sue and Noralane Lindor and Couch, {Fergus J.} and Marc Tischkowitz and Lenka Foretova and Joseph Vijai and Kenneth Offit and Singer, {Christian F.} and Christine Rappaport and Catherine MPhelan and Greene, {Mark H.} and Mai, {Phuong L.} and Gad Rennert and Imyanitov, {Evgeny N.} and Hulick, {Peter J.} and Phillips, {Kelly Anne} and Marion Piedmonte and Mulligan, {Anna Marie} and Gord Glendon and Anders Bojesen and Mads Thomassen and Caligo, {Maria A.} and Yoon, {Sook Yee} and Eitan Friedman and Yael Laitman and Ake Borg and {Von Wachenfeldt}, Anna and Hans Ehrencrona and Johanna Rantala and Olopade, {Olufunmilayo I.} and Ganz, {Patricia A.} and Nussbaum, {Robert L.} and Gayther, {Simon A.} and Katherine LNathanson and Domchek, {Susan M.} and Arun, {Banu K.} and Gillian Mitchell and Karlan, {Beth Y.} and Jenny Lester and Gertraud Maskarinec and Christy Woolcott and Christopher Scott and Jennifer Stone and Carmel Apicella and Rulla Tamimi and Robert Luben and Khaw, {Kay Tee} and Slaug Helland and Vilde Haakensen and Mitch Dowsett and Pharoah, {Paul D.P.} and Jacques Simard and Per Hall and Montserrat Garca-Closas and Celine Vachon and Georgia Chenevix-Trench and Antoniou, {Antonis C.} and Easton, {Douglas F.} and Edwards, {Stacey L.}",

note = "Publisher Copyright: {\textcopyright} 2016 Nature America, Inc.",

year = "2016",

month = mar,

day = "29",

doi = "10.1038/ng.3521",

language = "English (US)",

volume = "48",

pages = "374--386",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "4",

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TY - JOUR

T1 - Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170

AU - Dunning, Alison M.

AU - Michailidou, Kyriaki

AU - Kuchenbaecker, Karoline B.

AU - Thompson, Deborah

AU - French, Juliet D.

AU - Beesley, Jonathan

AU - Healey, Catherine S.

AU - Kar, Siddhartha

AU - Pooley, Karen A.

AU - Lopez-Knowles, Elena

AU - Dicks, Ed

AU - Barrowdale, Daniel

AU - Sinnott-Armstrong, Nicholas A.

AU - Sallari, Richard C.

AU - Hillman, Kristine M.

AU - Kaufmann, Susanne

AU - Sivakumaran, Haran

AU - Marjaneh, Mahdi Moradi

AU - Lee, Jason S.

AU - Hills, Margaret

AU - Jarosz, Monika

AU - Drury, Suzie

AU - Canisius, Sander

AU - KBolla, Manjeet

AU - Dennis, Joe

AU - Wang, Qin

AU - LHopper, John

AU - Southey, Melissa C.

AU - Broeks, Annegien

AU - Schmidt, Marjanka K.

AU - Lophatananon, Artitaya

AU - Muir, Kenneth

AU - Beckmann, Matthias W.

AU - Fasching, Peter A.

AU - Dos-Santos-Silva, Isabel

AU - Peto, Julian

AU - Sawyer, Elinor J.

AU - Tomlinson, Ian

AU - Burwinkel, Barbara

AU - Marme, Frederik

AU - Guénel, Pascal

AU - Truong, Thérse

AU - Bojesen, Stig E.

AU - Flyger, Henrik

AU - Gonzlez-Neira, Anna

AU - Perez, Jose I.A.

AU - Anton-Culver, Hoda

AU - Eunjung, Lee

AU - Arndt, Volker

AU - Brenner, Hermann

AU - Meindl, Alfons

AU - Schmutzler, Rita K.

AU - Brauch, Hiltrud

AU - Hamann, Ute

AU - Aittomki, Kristiina

AU - Blomqvist, Carl

AU - Ito, Hidemi

AU - Matsuo, Keitaro

AU - Bogdanova, Natasha

AU - Dörk, Thilo

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Kosma, Veli Matti

AU - Mannermaa, Arto

AU - Tseng, Chiu Chen

AU - Wu, Anna H.

AU - Lambrechts, Diether

AU - Wildiers, Hans

AU - Chang-Claude, Jenny

AU - Rudolph, Anja

AU - Peterlongo, Paolo

AU - Radice, Paolo

AU - EOlson, Janet

AU - GGiles, Graham

AU - Milne, Roger L.

AU - Haiman, Christopher A.

AU - Henderson, Brian E.

AU - Goldberg, Mark S.

AU - Teo, Soo H.

AU - Yip, Cheng Har

AU - Nord, Silje

AU - Borresen-Dale, Anne Lise

AU - Kristensen, Vessela

AU - Long, Jirong

AU - Zheng, Wei

AU - Pylks, Katri

AU - Winqvist, Robert

AU - Andrulis, Irene L.

AU - Knight, Julia A.

AU - Devilee, Peter

AU - Seynaeve, Caroline

AU - Figueroa, Jonine

AU - Sherman, Mark E.

AU - Czene, Kamila

AU - Darabi, Hatef

AU - Hollestelle, Antoinette

AU - Van Den Ouweland, Ans M.W.

AU - Humphreys, Keith

AU - Gao, Yu Tang

AU - Shu, Xiao Ou

AU - Cox, Angela

AU - Cross, Simon S.

AU - Blot, William

AU - Cai, Qiuyin

AU - Ghoussaini, Maya

AU - Perkins, Barbara J.

AU - Shah, Mitul

AU - Choi, Ji Yeob

AU - Kang, Daehee

AU - Lee, Soo Chin

AU - Hartman, Mikael

AU - Kabisch, Maria

AU - Torres, Diana

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Brennan, Paul

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PY - 2016/3/29

Y1 - 2016/3/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84962106221&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962106221&partnerID=8YFLogxK

U2 - 10.1038/ng.3521

DO - 10.1038/ng.3521

M3 - Article

C2 - 26928228

AN - SCOPUS:84962106221

SN - 1061-4036

VL - 48

SP - 374

EP - 386

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170

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