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Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1

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Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1. / Glubb, Dylan M; Maranian, Mel J; Michailidou, Kyriaki; Pooley, Karen A; Meyer, Kerstin B; Kar, Siddhartha; Carlebur, Saskia; O'Reilly, Martin; Betts, Joshua A; Hillman, Kristine M; Kaufmann, Susanne; Beesley, Jonathan; Canisius, Sander; Hopper, John L; Southey, Melissa C; Tsimiklis, Helen; Apicella, Carmel; Schmidt, Marjanka K; Broeks, Annegien; Hogervorst, Frans B; van der Schoot, C Ellen; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A; Ruebner, Matthias; Ekici, Arif B; Beckmann, Matthias W; Peto, Julian; dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Pharoah, Paul D P; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Burwinkel, Barbara; Marme, Frederik; Yang, Rongxi; Surowy, Harald; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; González-Neira, Anna; Benitez, Javier; Zamora, M Pilar; Arias Perez, Jose Ignacio; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Ko, Yon-Dschun; Brüning, Thomas; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tanaka, Hideo; Dörk, Thilo; Bogdanova, Natalia V; Helbig, Sonja; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Wu, Anna H; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O; Lambrechts, Diether; Zhao, Hui; Weltens, Caroline; van Limbergen, Erik; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Seibold, Petra; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Capra, Fabio; Couch, Fergus J; Olson, Janet E; Hallberg, Emily; Vachon, Celine; Giles, Graham G; Milne, Roger L; McLean, Catriona; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; See, Mee-Hoong; Cornes, Belinda; Cheng, Ching-Yu; Ikram, M Kamran; Kristensen, Vessela; Zheng, Wei; Halverson, Sandra L; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Van Asperen, Christi J; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J; Lissowska, Jolanta; Czene, Kamila; Klevebring, Daniel; Darabi, Hatef; Eriksson, Mikael; Hooning, Maartje J; Hollestelle, Antoinette; Martens, John W M; Collée, J Margriet; Hall, Per; Li, Jingmei; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Blot, William; Signorello, Lisa B; Cai, Qiuyin; Shah, Mitul; Ghoussaini, Maya; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Noh, Dong-Young; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Tang, Anthony; Hamann, Ute; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Olswold, Curtis; Slager, Susan; Toland, Amanda E; Yannoukakos, Drakoulis; Shen, Chen-Yang; Wu, Pei-Ei; Yu, Jyh-Cherng; Hou, Ming-Feng; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Pita, Guillermo; Alonso, M Rosario; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S; Brown, Melissa A; Ponder, Bruce A J; Chenevix-Trench, Georgia; Thompson, Deborah J; Edwards, Stacey L; Easton, Douglas F; Dunning, Alison M; French, Juliet D; GENICA Network.

in: AM J HUM GENET, Jahrgang 96, Nr. 1, 08.01.2015, S. 5-20.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Glubb, DM, Maranian, MJ, Michailidou, K, Pooley, KA, Meyer, KB, Kar, S, Carlebur, S, O'Reilly, M, Betts, JA, Hillman, KM, Kaufmann, S, Beesley, J, Canisius, S, Hopper, JL, Southey, MC, Tsimiklis, H, Apicella, C, Schmidt, MK, Broeks, A, Hogervorst, FB, van der Schoot, CE, Muir, K, Lophatananon, A, Stewart-Brown, S, Siriwanarangsan, P, Fasching, PA, Ruebner, M, Ekici, AB, Beckmann, MW, Peto, J, dos-Santos-Silva, I, Fletcher, O, Johnson, N, Pharoah, PDP, Bolla, MK, Wang, Q, Dennis, J, Sawyer, EJ, Tomlinson, I, Kerin, MJ, Miller, N, Burwinkel, B, Marme, F, Yang, R, Surowy, H, Guénel, P, Truong, T, Menegaux, F, Sanchez, M, Bojesen, SE, Nordestgaard, BG, Nielsen, SF, Flyger, H, González-Neira, A, Benitez, J, Zamora, MP, Arias Perez, JI, Anton-Culver, H, Neuhausen, SL, Brenner, H, Dieffenbach, AK, Arndt, V, Stegmaier, C, Meindl, A, Schmutzler, RK, Brauch, H, Ko, Y-D, Brüning, T, Nevanlinna, H, Muranen, TA, Aittomäki, K, Blomqvist, C, Matsuo, K, Ito, H, Iwata, H, Tanaka, H, Dörk, T, Bogdanova, NV, Helbig, S, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Wu, AH, Tseng, C, Van Den Berg, D, Stram, DO, Lambrechts, D, Zhao, H, Weltens, C, van Limbergen, E, Chang-Claude, J, Flesch-Janys, D, Rudolph, A, Seibold, P, Radice, P, Peterlongo, P, Barile, M, Capra, F, Couch, FJ, Olson, JE, Hallberg, E, Vachon, C, Giles, GG, Milne, RL, McLean, C, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Simard, J, Goldberg, MS, Labrèche, F, Dumont, M, Teo, SH, Yip, CH, See, M-H, Cornes, B, Cheng, C-Y, Ikram, MK, Kristensen, V, Zheng, W, Halverson, SL, Shrubsole, M, Long, J, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Kauppila, S, Andrulis, IL, Knight, JA, Glendon, G, Tchatchou, S, Devilee, P, Tollenaar, RAEM, Seynaeve, C, Van Asperen, CJ, García-Closas, M, Figueroa, J, Chanock, SJ, Lissowska, J, Czene, K, Klevebring, D, Darabi, H, Eriksson, M, Hooning, MJ, Hollestelle, A, Martens, JWM, Collée, JM, Hall, P, Li, J, Humphreys, K, Shu, X-O, Lu, W, Gao, Y-T, Cai, H, Cox, A, Cross, SS, Reed, MWR, Blot, W, Signorello, LB, Cai, Q, Shah, M, Ghoussaini, M, Kang, D, Choi, J-Y, Park, SK, Noh, D-Y, Hartman, M, Miao, H, Lim, WY, Tang, A, Hamann, U, Torres, D, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Sangrajrang, S, Gaborieau, V, Brennan, P, McKay, J, Olswold, C, Slager, S, Toland, AE, Yannoukakos, D, Shen, C-Y, Wu, P-E, Yu, J-C, Hou, M-F, Swerdlow, A, Ashworth, A, Orr, N, Jones, M, Pita, G, Alonso, MR, Álvarez, N, Herrero, D, Tessier, DC, Vincent, D, Bacot, F, Luccarini, C, Baynes, C, Ahmed, S, Healey, CS, Brown, MA, Ponder, BAJ, Chenevix-Trench, G, Thompson, DJ, Edwards, SL, Easton, DF, Dunning, AM, French, JD & GENICA Network 2015, 'Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1', AM J HUM GENET, Jg. 96, Nr. 1, S. 5-20. https://doi.org/10.1016/j.ajhg.2014.11.009

APA

Glubb, D. M., Maranian, M. J., Michailidou, K., Pooley, K. A., Meyer, K. B., Kar, S., Carlebur, S., O'Reilly, M., Betts, J. A., Hillman, K. M., Kaufmann, S., Beesley, J., Canisius, S., Hopper, J. L., Southey, M. C., Tsimiklis, H., Apicella, C., Schmidt, M. K., Broeks, A., ... GENICA Network (2015). Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1. AM J HUM GENET, 96(1), 5-20. https://doi.org/10.1016/j.ajhg.2014.11.009

Vancouver

Glubb DM, Maranian MJ, Michailidou K, Pooley KA, Meyer KB, Kar S et al. Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1. AM J HUM GENET. 2015 Jan 8;96(1):5-20. https://doi.org/10.1016/j.ajhg.2014.11.009

Bibtex

@article{99827d0dacc74efdb47d482a484ed169,
title = "Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1",
abstract = "Genome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer individuals and control individuals from 52 studies in the Breast Cancer Association Consortium. Multiple logistic regression analyses identified three independent risk signals: the strongest associations were with 15 correlated variants (iCHAV1), where the minor allele of the best candidate, rs62355902, associated with significantly increased risks of both estrogen-receptor-positive (ER(+): odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.21-1.27, ptrend = 5.7 × 10(-44)) and estrogen-receptor-negative (ER(-): OR = 1.10, 95% CI = 1.05-1.15, ptrend = 3.0 × 10(-4)) tumors. After adjustment for rs62355902, we found evidence of association of a further 173 variants (iCHAV2) containing three subsets with a range of effects (the strongest was rs113317823 [pcond = 1.61 × 10(-5)]) and five variants composing iCHAV3 (lead rs11949391; ER(+): OR = 0.90, 95% CI = 0.87-0.93, pcond = 1.4 × 10(-4)). Twenty-six percent of the prioritized candidate variants coincided with four putative regulatory elements that interact with the MAP3K1 promoter through chromatin looping and affect MAP3K1 promoter activity. Functional analysis indicated that the cancer risk alleles of four candidates (rs74345699 and rs62355900 [iCHAV1], rs16886397 [iCHAV2a], and rs17432750 [iCHAV3]) increased MAP3K1 transcriptional activity. Chromatin immunoprecipitation analysis revealed diminished GATA3 binding to the minor (cancer-protective) allele of rs17432750, indicating a mechanism for its action. We propose that the cancer risk alleles act to increase MAP3K1 expression in vivo and might promote breast cancer cell survival.",
keywords = "Alleles, Breast Neoplasms, Case-Control Studies, Cell Line, Tumor, Chromosome Mapping, Chromosomes, Human, Pair 5, Continental Population Groups, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotyping Techniques, Humans, MAP Kinase Kinase Kinase 1, MCF-7 Cells, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Quantitative Trait Loci, Risk Factors",
author = "Glubb, {Dylan M} and Maranian, {Mel J} and Kyriaki Michailidou and Pooley, {Karen A} and Meyer, {Kerstin B} and Siddhartha Kar and Saskia Carlebur and Martin O'Reilly and Betts, {Joshua A} and Hillman, {Kristine M} and Susanne Kaufmann and Jonathan Beesley and Sander Canisius and Hopper, {John L} and Southey, {Melissa C} and Helen Tsimiklis and Carmel Apicella and Schmidt, {Marjanka K} and Annegien Broeks and Hogervorst, {Frans B} and {van der Schoot}, {C Ellen} and Kenneth Muir and Artitaya Lophatananon and Sarah Stewart-Brown and Pornthep Siriwanarangsan and Fasching, {Peter A} and Matthias Ruebner and Ekici, {Arif B} and Beckmann, {Matthias W} and Julian Peto and Isabel dos-Santos-Silva and Olivia Fletcher and Nichola Johnson and Pharoah, {Paul D P} and Bolla, {Manjeet K} and Qin Wang and Joe Dennis and Sawyer, {Elinor J} and Ian Tomlinson and Kerin, {Michael J} and Nicola Miller and Barbara Burwinkel and Frederik Marme and Rongxi Yang and Harald Surowy and Pascal Gu{\'e}nel and Th{\'e}r{\`e}se Truong and Florence Menegaux and Marie Sanchez and Bojesen, {Stig E} and Nordestgaard, {B{\o}rge G} and Nielsen, {Sune F} and Henrik Flyger and Anna Gonz{\'a}lez-Neira and Javier Benitez and Zamora, {M Pilar} and {Arias Perez}, {Jose Ignacio} and Hoda Anton-Culver and Neuhausen, {Susan L} and Hermann Brenner and Dieffenbach, {Aida Karina} and Volker Arndt and Christa Stegmaier and Alfons Meindl and Schmutzler, {Rita K} and Hiltrud Brauch and Yon-Dschun Ko and Thomas Br{\"u}ning and Heli Nevanlinna and Muranen, {Taru A} and Kristiina Aittom{\"a}ki and Carl Blomqvist and Keitaro Matsuo and Hidemi Ito and Hiroji Iwata and Hideo Tanaka and Thilo D{\"o}rk and Bogdanova, {Natalia V} and Sonja Helbig and Annika Lindblom and Sara Margolin and Arto Mannermaa and Vesa Kataja and Veli-Matti Kosma and Hartikainen, {Jaana M} and Wu, {Anna H} and Chiu-chen Tseng and {Van Den Berg}, David and Stram, {Daniel O} and Diether Lambrechts and Hui Zhao and Caroline Weltens and {van Limbergen}, Erik and Jenny Chang-Claude and Dieter Flesch-Janys and Anja Rudolph and Petra Seibold and Paolo Radice and Paolo Peterlongo and Monica Barile and Fabio Capra and Couch, {Fergus J} and Olson, {Janet E} and Emily Hallberg and Celine Vachon and Giles, {Graham G} and Milne, {Roger L} and Catriona McLean and Haiman, {Christopher A} and Henderson, {Brian E} and Fredrick Schumacher and {Le Marchand}, Loic and Jacques Simard and Goldberg, {Mark S} and France Labr{\`e}che and Martine Dumont and Teo, {Soo Hwang} and Yip, {Cheng Har} and Mee-Hoong See and Belinda Cornes and Ching-Yu Cheng and Ikram, {M Kamran} and Vessela Kristensen and Wei Zheng and Halverson, {Sandra L} and Martha Shrubsole and Jirong Long and Robert Winqvist and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Saila Kauppila and Andrulis, {Irene L} and Knight, {Julia A} and Gord Glendon and Sandrine Tchatchou and Peter Devilee and Tollenaar, {Robert A E M} and Caroline Seynaeve and {Van Asperen}, {Christi J} and Montserrat Garc{\'i}a-Closas and Jonine Figueroa and Chanock, {Stephen J} and Jolanta Lissowska and Kamila Czene and Daniel Klevebring and Hatef Darabi and Mikael Eriksson and Hooning, {Maartje J} and Antoinette Hollestelle and Martens, {John W M} and Coll{\'e}e, {J Margriet} and Per Hall and Jingmei Li and Keith Humphreys and Xiao-Ou Shu and Wei Lu and Yu-Tang Gao and Hui Cai and Angela Cox and Cross, {Simon S} and Reed, {Malcolm W R} and William Blot and Signorello, {Lisa B} and Qiuyin Cai and Mitul Shah and Maya Ghoussaini and Daehee Kang and Ji-Yeob Choi and Park, {Sue K} and Dong-Young Noh and Mikael Hartman and Hui Miao and Lim, {Wei Yen} and Anthony Tang and Ute Hamann and Diana Torres and Anna Jakubowska and Jan Lubinski and Katarzyna Jaworska and Katarzyna Durda and Suleeporn Sangrajrang and Valerie Gaborieau and Paul Brennan and James McKay and Curtis Olswold and Susan Slager and Toland, {Amanda E} and Drakoulis Yannoukakos and Chen-Yang Shen and Pei-Ei Wu and Jyh-Cherng Yu and Ming-Feng Hou and Anthony Swerdlow and Alan Ashworth and Nick Orr and Michael Jones and Guillermo Pita and Alonso, {M Rosario} and Nuria {\'A}lvarez and Daniel Herrero and Tessier, {Daniel C} and Daniel Vincent and Francois Bacot and Craig Luccarini and Caroline Baynes and Shahana Ahmed and Healey, {Catherine S} and Brown, {Melissa A} and Ponder, {Bruce A J} and Georgia Chenevix-Trench and Thompson, {Deborah J} and Edwards, {Stacey L} and Easton, {Douglas F} and Dunning, {Alison M} and French, {Juliet D} and {GENICA Network}",
note = "Copyright {\textcopyright} 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.",
year = "2015",
month = jan,
day = "8",
doi = "10.1016/j.ajhg.2014.11.009",
language = "English",
volume = "96",
pages = "5--20",
journal = "AM J HUM GENET",
issn = "0002-9297",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1

AU - Glubb, Dylan M

AU - Maranian, Mel J

AU - Michailidou, Kyriaki

AU - Pooley, Karen A

AU - Meyer, Kerstin B

AU - Kar, Siddhartha

AU - Carlebur, Saskia

AU - O'Reilly, Martin

AU - Betts, Joshua A

AU - Hillman, Kristine M

AU - Kaufmann, Susanne

AU - Beesley, Jonathan

AU - Canisius, Sander

AU - Hopper, John L

AU - Southey, Melissa C

AU - Tsimiklis, Helen

AU - Apicella, Carmel

AU - Schmidt, Marjanka K

AU - Broeks, Annegien

AU - Hogervorst, Frans B

AU - van der Schoot, C Ellen

AU - Muir, Kenneth

AU - Lophatananon, Artitaya

AU - Stewart-Brown, Sarah

AU - Siriwanarangsan, Pornthep

AU - Fasching, Peter A

AU - Ruebner, Matthias

AU - Ekici, Arif B

AU - Beckmann, Matthias W

AU - Peto, Julian

AU - dos-Santos-Silva, Isabel

AU - Fletcher, Olivia

AU - Johnson, Nichola

AU - Pharoah, Paul D P

AU - Bolla, Manjeet K

AU - Wang, Qin

AU - Dennis, Joe

AU - Sawyer, Elinor J

AU - Tomlinson, Ian

AU - Kerin, Michael J

AU - Miller, Nicola

AU - Burwinkel, Barbara

AU - Marme, Frederik

AU - Yang, Rongxi

AU - Surowy, Harald

AU - Guénel, Pascal

AU - Truong, Thérèse

AU - Menegaux, Florence

AU - Sanchez, Marie

AU - Bojesen, Stig E

AU - Nordestgaard, Børge G

AU - Nielsen, Sune F

AU - Flyger, Henrik

AU - González-Neira, Anna

AU - Benitez, Javier

AU - Zamora, M Pilar

AU - Arias Perez, Jose Ignacio

AU - Anton-Culver, Hoda

AU - Neuhausen, Susan L

AU - Brenner, Hermann

AU - Dieffenbach, Aida Karina

AU - Arndt, Volker

AU - Stegmaier, Christa

AU - Meindl, Alfons

AU - Schmutzler, Rita K

AU - Brauch, Hiltrud

AU - Ko, Yon-Dschun

AU - Brüning, Thomas

AU - Nevanlinna, Heli

AU - Muranen, Taru A

AU - Aittomäki, Kristiina

AU - Blomqvist, Carl

AU - Matsuo, Keitaro

AU - Ito, Hidemi

AU - Iwata, Hiroji

AU - Tanaka, Hideo

AU - Dörk, Thilo

AU - Bogdanova, Natalia V

AU - Helbig, Sonja

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Mannermaa, Arto

AU - Kataja, Vesa

AU - Kosma, Veli-Matti

AU - Hartikainen, Jaana M

AU - Wu, Anna H

AU - Tseng, Chiu-chen

AU - Van Den Berg, David

AU - Stram, Daniel O

AU - Lambrechts, Diether

AU - Zhao, Hui

AU - Weltens, Caroline

AU - van Limbergen, Erik

AU - Chang-Claude, Jenny

AU - Flesch-Janys, Dieter

AU - Rudolph, Anja

AU - Seibold, Petra

AU - Radice, Paolo

AU - Peterlongo, Paolo

AU - Barile, Monica

AU - Capra, Fabio

AU - Couch, Fergus J

AU - Olson, Janet E

AU - Hallberg, Emily

AU - Vachon, Celine

AU - Giles, Graham G

AU - Milne, Roger L

AU - McLean, Catriona

AU - Haiman, Christopher A

AU - Henderson, Brian E

AU - Schumacher, Fredrick

AU - Le Marchand, Loic

AU - Simard, Jacques

AU - Goldberg, Mark S

AU - Labrèche, France

AU - Dumont, Martine

AU - Teo, Soo Hwang

AU - Yip, Cheng Har

AU - See, Mee-Hoong

AU - Cornes, Belinda

AU - Cheng, Ching-Yu

AU - Ikram, M Kamran

AU - Kristensen, Vessela

AU - Zheng, Wei

AU - Halverson, Sandra L

AU - Shrubsole, Martha

AU - Long, Jirong

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Jukkola-Vuorinen, Arja

AU - Kauppila, Saila

AU - Andrulis, Irene L

AU - Knight, Julia A

AU - Glendon, Gord

AU - Tchatchou, Sandrine

AU - Devilee, Peter

AU - Tollenaar, Robert A E M

AU - Seynaeve, Caroline

AU - Van Asperen, Christi J

AU - García-Closas, Montserrat

AU - Figueroa, Jonine

AU - Chanock, Stephen J

AU - Lissowska, Jolanta

AU - Czene, Kamila

AU - Klevebring, Daniel

AU - Darabi, Hatef

AU - Eriksson, Mikael

AU - Hooning, Maartje J

AU - Hollestelle, Antoinette

AU - Martens, John W M

AU - Collée, J Margriet

AU - Hall, Per

AU - Li, Jingmei

AU - Humphreys, Keith

AU - Shu, Xiao-Ou

AU - Lu, Wei

AU - Gao, Yu-Tang

AU - Cai, Hui

AU - Cox, Angela

AU - Cross, Simon S

AU - Reed, Malcolm W R

AU - Blot, William

AU - Signorello, Lisa B

AU - Cai, Qiuyin

AU - Shah, Mitul

AU - Ghoussaini, Maya

AU - Kang, Daehee

AU - Choi, Ji-Yeob

AU - Park, Sue K

AU - Noh, Dong-Young

AU - Hartman, Mikael

AU - Miao, Hui

AU - Lim, Wei Yen

AU - Tang, Anthony

AU - Hamann, Ute

AU - Torres, Diana

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Jaworska, Katarzyna

AU - Durda, Katarzyna

AU - Sangrajrang, Suleeporn

AU - Gaborieau, Valerie

AU - Brennan, Paul

AU - McKay, James

AU - Olswold, Curtis

AU - Slager, Susan

AU - Toland, Amanda E

AU - Yannoukakos, Drakoulis

AU - Shen, Chen-Yang

AU - Wu, Pei-Ei

AU - Yu, Jyh-Cherng

AU - Hou, Ming-Feng

AU - Swerdlow, Anthony

AU - Ashworth, Alan

AU - Orr, Nick

AU - Jones, Michael

AU - Pita, Guillermo

AU - Alonso, M Rosario

AU - Álvarez, Nuria

AU - Herrero, Daniel

AU - Tessier, Daniel C

AU - Vincent, Daniel

AU - Bacot, Francois

AU - Luccarini, Craig

AU - Baynes, Caroline

AU - Ahmed, Shahana

AU - Healey, Catherine S

AU - Brown, Melissa A

AU - Ponder, Bruce A J

AU - Chenevix-Trench, Georgia

AU - Thompson, Deborah J

AU - Edwards, Stacey L

AU - Easton, Douglas F

AU - Dunning, Alison M

AU - French, Juliet D

AU - GENICA Network

N1 - Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

PY - 2015/1/8

Y1 - 2015/1/8

N2 - Genome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer individuals and control individuals from 52 studies in the Breast Cancer Association Consortium. Multiple logistic regression analyses identified three independent risk signals: the strongest associations were with 15 correlated variants (iCHAV1), where the minor allele of the best candidate, rs62355902, associated with significantly increased risks of both estrogen-receptor-positive (ER(+): odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.21-1.27, ptrend = 5.7 × 10(-44)) and estrogen-receptor-negative (ER(-): OR = 1.10, 95% CI = 1.05-1.15, ptrend = 3.0 × 10(-4)) tumors. After adjustment for rs62355902, we found evidence of association of a further 173 variants (iCHAV2) containing three subsets with a range of effects (the strongest was rs113317823 [pcond = 1.61 × 10(-5)]) and five variants composing iCHAV3 (lead rs11949391; ER(+): OR = 0.90, 95% CI = 0.87-0.93, pcond = 1.4 × 10(-4)). Twenty-six percent of the prioritized candidate variants coincided with four putative regulatory elements that interact with the MAP3K1 promoter through chromatin looping and affect MAP3K1 promoter activity. Functional analysis indicated that the cancer risk alleles of four candidates (rs74345699 and rs62355900 [iCHAV1], rs16886397 [iCHAV2a], and rs17432750 [iCHAV3]) increased MAP3K1 transcriptional activity. Chromatin immunoprecipitation analysis revealed diminished GATA3 binding to the minor (cancer-protective) allele of rs17432750, indicating a mechanism for its action. We propose that the cancer risk alleles act to increase MAP3K1 expression in vivo and might promote breast cancer cell survival.

AB - Genome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer individuals and control individuals from 52 studies in the Breast Cancer Association Consortium. Multiple logistic regression analyses identified three independent risk signals: the strongest associations were with 15 correlated variants (iCHAV1), where the minor allele of the best candidate, rs62355902, associated with significantly increased risks of both estrogen-receptor-positive (ER(+): odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.21-1.27, ptrend = 5.7 × 10(-44)) and estrogen-receptor-negative (ER(-): OR = 1.10, 95% CI = 1.05-1.15, ptrend = 3.0 × 10(-4)) tumors. After adjustment for rs62355902, we found evidence of association of a further 173 variants (iCHAV2) containing three subsets with a range of effects (the strongest was rs113317823 [pcond = 1.61 × 10(-5)]) and five variants composing iCHAV3 (lead rs11949391; ER(+): OR = 0.90, 95% CI = 0.87-0.93, pcond = 1.4 × 10(-4)). Twenty-six percent of the prioritized candidate variants coincided with four putative regulatory elements that interact with the MAP3K1 promoter through chromatin looping and affect MAP3K1 promoter activity. Functional analysis indicated that the cancer risk alleles of four candidates (rs74345699 and rs62355900 [iCHAV1], rs16886397 [iCHAV2a], and rs17432750 [iCHAV3]) increased MAP3K1 transcriptional activity. Chromatin immunoprecipitation analysis revealed diminished GATA3 binding to the minor (cancer-protective) allele of rs17432750, indicating a mechanism for its action. We propose that the cancer risk alleles act to increase MAP3K1 expression in vivo and might promote breast cancer cell survival.

KW - Alleles

KW - Breast Neoplasms

KW - Case-Control Studies

KW - Cell Line, Tumor

KW - Chromosome Mapping

KW - Chromosomes, Human, Pair 5

KW - Continental Population Groups

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotyping Techniques

KW - Humans

KW - MAP Kinase Kinase Kinase 1

KW - MCF-7 Cells

KW - Polymorphism, Single Nucleotide

KW - Promoter Regions, Genetic

KW - Quantitative Trait Loci

KW - Risk Factors

U2 - 10.1016/j.ajhg.2014.11.009

DO - 10.1016/j.ajhg.2014.11.009

M3 - SCORING: Journal article

C2 - 25529635

VL - 96

SP - 5

EP - 20

JO - AM J HUM GENET

JF - AM J HUM GENET

SN - 0002-9297

IS - 1

ER -