Fine-scale mapping of the 4q24 locus identifies & pr two Independent loci associated with breast cancer risk

Xingyi Guo, Jirong Long, Chenjie Zeng, Kyriaki Michailidou, Maya Ghoussaini, Manjeet K. Bolla, Qin Wang, Roger L. Milne, Xiao Ou Shu, Qiuyin Cai, Jonathan Beesley, Siddhartha P. Kar, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Matthias W. Beckmann, Alicia Beeghly-Fadiel, Javier Benitez, William Blot, Natalia BogdanovaStig E. Bojesen, Hiltrud Brauch, Hermann Brenner, Louise Brinton, Annegien Broekss, Thomas Bruning, Barbara Burwinkel, Hui Cai, Sander Canisius, Jenny Chang-Claude, Ji Yeob Choi, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Hatef Darabi, Peter Devilee, Arnaud Droit, Thilo Dork, Peter A. Fasching, Olivia Fletcher, Henrik Flyger, Florentia Fostira, Valerie Gaborieau, Montserrat García-Closas, Graham G. Giles, Mervi Grip, Pascal Guenel, Christopher A. Haiman, Ute Hamann, Mikael Hartman, Antoinette Hollestelle, John L. Hopper, Chia Ni Hsiung, Hidemi Ito, Anna Jakubowska, Nichola Johnson, Maria Kabisch, Daehee Kang, Sofia Khan, Julia A. Knight, Veli Matti Kosma, Diether Lambrechts, Loic Le Marchand, Jingmei Li, Annika Lindblom, Artitaya Lophatananon, Jan Lubinski, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, Frederik Marme, Keitaro Matsuo, Catriona A. McLean, Alfons Meindl, Kenneth Muir, Susan L. Neuhausen, Heli Nevanlinna, Silje Nord, Janet E. Olson, Nick Orr, Paolo Peterlongo, Thomas Choudary Putti, Anja Rudolph, Suleeporn Sangrajrang, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Chen Yang Shen, Jiajun Shi, Martha J. Shrubsole, Melissa C. Southey, Anthony Swerdlow, Soo Hwang Teo, Bernard Thienpont, Amanda Ewart Toland, Robert A E M Tollenaar, Ian P M Tomlinson, Therese Truong, Chiu Chen Tseng, Ans Van Den Ouweland, Wanqing Wen, Robert Winqvist, Anna Wu, Cheng Har Yip, M. Pilar Zamora, Ying Zheng, Per Hall, Paul D P Pharoah, Jacques Simard, Georgia Chenevix-Trench, Alison M. Dunning, Douglas F. Easton, Wei Zheng, Rosalind A. Eeles, Ali Amin Al Olama, Zsofia Kote-Jarai, Sara Benlloch, Antonis Antoniou, Lesley McGuffog, Ken Offit, Andrew Lee, Ed Dicks, Craig Luccarini, Daniel C. Tessier, Francois Bacot, Daniel Vincent, Sylvie La Boissière, Frederic Robidoux, Sune F. Nielsen, Julie M. Cunningham, Sharon A. Windebank, Christopher A. Hilker, Jeffrey Meyer, Maggie Angelakos, Judi Maskiell, Ellen Van Der Schoot, Emiel Rutgers, Senno Verhoef, Frans Hogervorst, Prat Boonyawongviroj, Pornthep Siriwanarungsan, Michael Schrauder, Matthias Rübner, Sonja Oeser, Silke Landrith, Eileen Williams, Elaine Ryder-Mills, Kara Sargus, Niall McInerney, Gabrielle Colleran, Andrew Rowan, Angela Jones, Christof Sohn, Andeas Schneeweiß, Peter Bugert, Núria Álvarez, Leslie Bernstein, James Lacey, Sophia Wang, Huiyan Ma, Yani Lu, Jessica Clague De Hart, Dennis Deapen, Rich Pinder, Eunjung Lee, Fred Schumacher, Pam Horn-Ross, Peggy Reynolds, David Nelson, Hannah Park, Hartwig Ziegler, Sonja Wolf, Volker Hermann, Wing Yee Lo, Christina Justenhoven, Yon Dschun Ko, Christian Baisch, Hans Peter Fischer, Beate Pesch, Sylvia Rabstein, Anne Lotz, Volker Harth, Tuomas Heikkinen, Irja Erkkilä, Kirsimari Aaltonen, Karl Von Smitten, Natalia Antonenkova, Peter Hillemanns, Hans Christiansen, Eija Myöhänen, Helena Kemiläinen, Heather Thorne, Eveline Niedermayr, D. Bowtell, G. Chenevix-Trench, A. De Fazio, D. Gertig, A. Green, P. Webb, A. Green, P. Parsons, N. Hayward, P. Webb, D. Whiteman, Annie Fung, June Yashiki, Gilian Peuteman, Dominiek Smeets, Thomas Van Brussel, Kathleen Corthouts, Nadia Obi, Judith Heinz, Sabine Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers, Bernard Peissel, Giulietta Scuvera, Daniela Zaffaroni, Bernardo Bonanni, Irene Feroce, Angela Maniscalco, Alessandra Rossi, Loris Bernard, Martine Tranchant, Marie France Valois, Annie Turgeon, Lea Heguy, Phuah Sze Yee, Peter Kang, Kang In Nee, Shivaani Mariapun, Yoon Sook-Yee, Daphne Lee, Teh Yew Ching, Nur Aishah Mohd Taib, Meeri Otsukka, Kari Mononen, Teresa Selander, Nayana Weerasooriya, E. Krol-Warmerdam, J. Molenaar, J. Blom, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao, Michael Stagner, Petra Bos, Jannet Blom, Ellen Crepin, Anja Nieuwlaat, Annette Heemskerk, Sue Higham, Helen Cramp, Dan Connley, Sabapathy Balasubramanian, Ian Brock, Michael Kerin, Nicola Miller, Pierre Kerbrat, Patrick Arveux, Romuald Le Scodan, Yves Raoul, Pierre Laurent-Puig, Claire Mulot, Christa Stegmaier, Katja Butterbach, Johann H. Karstens, Dieter Flesch-Janys, Petra Seibold, Alina Vrieling, Stefan Nickels, Paolo Radice, Katri Pylkäs, Arja Jukkola-Vuorinen, Saila Kauppila, Don Conroy, Caroline Baynes, Kimberley Chua, Robert Pilarski

Research output: Contribution to journalArticle

Abstract

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P=2.51 × 10-4; OR, 1.04; 95% confidence interval (CI), 1.02-1.07] and rs77928427 (P=1.86 × 10-4; OR, 1.04; 95% CI, 1.02-1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor-binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk.

Original languageEnglish
Pages (from-to)1680-1691
Number of pages12
JournalCancer Epidemiology Biomarkers and Prevention
Volume24
Issue number11
DOIs
Publication statusPublished - Nov 1 2015

Fingerprint

Breast Neoplasms
Confidence Intervals
Encyclopedias
Atlases
Deoxyribonuclease I
Linkage Disequilibrium
Sample Size
Hypersensitivity
Transcription Factors
Binding Sites
Genome
DNA
Genes
Neoplasms

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Fine-scale mapping of the 4q24 locus identifies & pr two Independent loci associated with breast cancer risk. / Guo, Xingyi; Long, Jirong; Zeng, Chenjie; Michailidou, Kyriaki; Ghoussaini, Maya; Bolla, Manjeet K.; Wang, Qin; Milne, Roger L.; Shu, Xiao Ou; Cai, Qiuyin; Beesley, Jonathan; Kar, Siddhartha P.; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W.; Beeghly-Fadiel, Alicia; Benitez, Javier; Blot, William; Bogdanova, Natalia; Bojesen, Stig E.; Brauch, Hiltrud; Brenner, Hermann; Brinton, Louise; Broekss, Annegien; Bruning, Thomas; Burwinkel, Barbara; Cai, Hui; Canisius, Sander; Chang-Claude, Jenny; Choi, Ji Yeob; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Darabi, Hatef; Devilee, Peter; Droit, Arnaud; Dork, Thilo; Fasching, Peter A.; Fletcher, Olivia; Flyger, Henrik; Fostira, Florentia; Gaborieau, Valerie; García-Closas, Montserrat; Giles, Graham G.; Grip, Mervi; Guenel, Pascal; Haiman, Christopher A.; Hamann, Ute; Hartman, Mikael; Hollestelle, Antoinette; Hopper, John L.; Hsiung, Chia Ni; Ito, Hidemi; Jakubowska, Anna; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Khan, Sofia; Knight, Julia A.; Kosma, Veli Matti; Lambrechts, Diether; Le Marchand, Loic; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Matsuo, Keitaro; McLean, Catriona A.; Meindl, Alfons; Muir, Kenneth; Neuhausen, Susan L.; Nevanlinna, Heli; Nord, Silje; Olson, Janet E.; Orr, Nick; Peterlongo, Paolo; Putti, Thomas Choudary; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Shen, Chen Yang; Shi, Jiajun; Shrubsole, Martha J.; Southey, Melissa C.; Swerdlow, Anthony; Teo, Soo Hwang; Thienpont, Bernard; Toland, Amanda Ewart; Tollenaar, Robert A E M; Tomlinson, Ian P M; Truong, Therese; Tseng, Chiu Chen; Van Den Ouweland, Ans; Wen, Wanqing; Winqvist, Robert; Wu, Anna; Yip, Cheng Har; Zamora, M. Pilar; Zheng, Ying; Hall, Per; Pharoah, Paul D P; Simard, Jacques; Chenevix-Trench, Georgia; Dunning, Alison M.; Easton, Douglas F.; Zheng, Wei; Eeles, Rosalind A.; Al Olama, Ali Amin; Kote-Jarai, Zsofia; Benlloch, Sara; Antoniou, Antonis; McGuffog, Lesley; Offit, Ken; Lee, Andrew; Dicks, Ed; Luccarini, Craig; Tessier, Daniel C.; Bacot, Francois; Vincent, Daniel; La Boissière, Sylvie; Robidoux, Frederic; Nielsen, Sune F.; Cunningham, Julie M.; Windebank, Sharon A.; Hilker, Christopher A.; Meyer, Jeffrey; Angelakos, Maggie; Maskiell, Judi; Van Der Schoot, Ellen; Rutgers, Emiel; Verhoef, Senno; Hogervorst, Frans; Boonyawongviroj, Prat; Siriwanarungsan, Pornthep; Schrauder, Michael; Rübner, Matthias; Oeser, Sonja; Landrith, Silke; Williams, Eileen; Ryder-Mills, Elaine; Sargus, Kara; McInerney, Niall; Colleran, Gabrielle; Rowan, Andrew; Jones, Angela; Sohn, Christof; Schneeweiß, Andeas; Bugert, Peter; Álvarez, Núria; Bernstein, Leslie; Lacey, James; Wang, Sophia; Ma, Huiyan; Lu, Yani; Clague De Hart, Jessica; Deapen, Dennis; Pinder, Rich; Lee, Eunjung; Schumacher, Fred; Horn-Ross, Pam; Reynolds, Peggy; Nelson, David; Park, Hannah; Ziegler, Hartwig; Wolf, Sonja; Hermann, Volker; Lo, Wing Yee; Justenhoven, Christina; Ko, Yon Dschun; Baisch, Christian; Fischer, Hans Peter; Pesch, Beate; Rabstein, Sylvia; Lotz, Anne; Harth, Volker; Heikkinen, Tuomas; Erkkilä, Irja; Aaltonen, Kirsimari; Von Smitten, Karl; Antonenkova, Natalia; Hillemanns, Peter; Christiansen, Hans; Myöhänen, Eija; Kemiläinen, Helena; Thorne, Heather; Niedermayr, Eveline; Bowtell, D.; Chenevix-Trench, G.; De Fazio, A.; Gertig, D.; Green, A.; Webb, P.; Green, A.; Parsons, P.; Hayward, N.; Webb, P.; Whiteman, D.; Fung, Annie; Yashiki, June; Peuteman, Gilian; Smeets, Dominiek; Van Brussel, Thomas; Corthouts, Kathleen; Obi, Nadia; Heinz, Judith; Behrens, Sabine; Eilber, Ursula; Celik, Muhabbet; Olchers, Til; Peissel, Bernard; Scuvera, Giulietta; Zaffaroni, Daniela; Bonanni, Bernardo; Feroce, Irene; Maniscalco, Angela; Rossi, Alessandra; Bernard, Loris; Tranchant, Martine; Valois, Marie France; Turgeon, Annie; Heguy, Lea; Yee, Phuah Sze; Kang, Peter; Nee, Kang In; Mariapun, Shivaani; Sook-Yee, Yoon; Lee, Daphne; Ching, Teh Yew; Taib, Nur Aishah Mohd; Otsukka, Meeri; Mononen, Kari; Selander, Teresa; Weerasooriya, Nayana; Krol-Warmerdam, E.; Molenaar, J.; Blom, J.; Szeszenia-Dabrowska, Neonila; Peplonska, Beata; Zatonski, Witold; Chao, Pei; Stagner, Michael; Bos, Petra; Blom, Jannet; Crepin, Ellen; Nieuwlaat, Anja; Heemskerk, Annette; Higham, Sue; Cramp, Helen; Connley, Dan; Balasubramanian, Sabapathy; Brock, Ian; Kerin, Michael; Miller, Nicola; Kerbrat, Pierre; Arveux, Patrick; Le Scodan, Romuald; Raoul, Yves; Laurent-Puig, Pierre; Mulot, Claire; Stegmaier, Christa; Butterbach, Katja; Karstens, Johann H.; Flesch-Janys, Dieter; Seibold, Petra; Vrieling, Alina; Nickels, Stefan; Radice, Paolo; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Conroy, Don; Baynes, Caroline; Chua, Kimberley; Pilarski, Robert.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 24, No. 11, 01.11.2015, p. 1680-1691.

Research output: Contribution to journalArticle

Guo, X, Long, J, Zeng, C, Michailidou, K, Ghoussaini, M, Bolla, MK, Wang, Q, Milne, RL, Shu, XO, Cai, Q, Beesley, J, Kar, SP, Andrulis, IL, Anton-Culver, H, Arndt, V, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Blot, W, Bogdanova, N, Bojesen, SE, Brauch, H, Brenner, H, Brinton, L, Broekss, A, Bruning, T, Burwinkel, B, Cai, H, Canisius, S, Chang-Claude, J, Choi, JY, Couch, FJ, Cox, A, Cross, SS, Czene, K, Darabi, H, Devilee, P, Droit, A, Dork, T, Fasching, PA, Fletcher, O, Flyger, H, Fostira, F, Gaborieau, V, García-Closas, M, Giles, GG, Grip, M, Guenel, P, Haiman, CA, Hamann, U, Hartman, M, Hollestelle, A, Hopper, JL, Hsiung, CN, Ito, H, Jakubowska, A, Johnson, N, Kabisch, M, Kang, D, Khan, S, Knight, JA, Kosma, VM, Lambrechts, D, Le Marchand, L, Li, J, Lindblom, A, Lophatananon, A, Lubinski, J, Mannermaa, A, Manoukian, S, Margolin, S, Marme, F, Matsuo, K, McLean, CA, Meindl, A, Muir, K, Neuhausen, SL, Nevanlinna, H, Nord, S, Olson, JE, Orr, N, Peterlongo, P, Putti, TC, Rudolph, A, Sangrajrang, S, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Shen, CY, Shi, J, Shrubsole, MJ, Southey, MC, Swerdlow, A, Teo, SH, Thienpont, B, Toland, AE, Tollenaar, RAEM, Tomlinson, IPM, Truong, T, Tseng, CC, Van Den Ouweland, A, Wen, W, Winqvist, R, Wu, A, Yip, CH, Zamora, MP, Zheng, Y, Hall, P, Pharoah, PDP, Simard, J, Chenevix-Trench, G, Dunning, AM, Easton, DF, Zheng, W, Eeles, RA, Al Olama, AA, Kote-Jarai, Z, Benlloch, S, Antoniou, A, McGuffog, L, Offit, K, Lee, A, Dicks, E, Luccarini, C, Tessier, DC, Bacot, F, Vincent, D, La Boissière, S, Robidoux, F, Nielsen, SF, Cunningham, JM, Windebank, SA, Hilker, CA, Meyer, J, Angelakos, M, Maskiell, J, Van Der Schoot, E, Rutgers, E, Verhoef, S, Hogervorst, F, Boonyawongviroj, P, Siriwanarungsan, P, Schrauder, M, Rübner, M, Oeser, S, Landrith, S, Williams, E, Ryder-Mills, E, Sargus, K, McInerney, N, Colleran, G, Rowan, A, Jones, A, Sohn, C, Schneeweiß, A, Bugert, P, Álvarez, N, Bernstein, L, Lacey, J, Wang, S, Ma, H, Lu, Y, Clague De Hart, J, Deapen, D, Pinder, R, Lee, E, Schumacher, F, Horn-Ross, P, Reynolds, P, Nelson, D, Park, H, Ziegler, H, Wolf, S, Hermann, V, Lo, WY, Justenhoven, C, Ko, YD, Baisch, C, Fischer, HP, Pesch, B, Rabstein, S, Lotz, A, Harth, V, Heikkinen, T, Erkkilä, I, Aaltonen, K, Von Smitten, K, Antonenkova, N, Hillemanns, P, Christiansen, H, Myöhänen, E, Kemiläinen, H, Thorne, H, Niedermayr, E, Bowtell, D, Chenevix-Trench, G, De Fazio, A, Gertig, D, Green, A, Webb, P, Green, A, Parsons, P, Hayward, N, Webb, P, Whiteman, D, Fung, A, Yashiki, J, Peuteman, G, Smeets, D, Van Brussel, T, Corthouts, K, Obi, N, Heinz, J, Behrens, S, Eilber, U, Celik, M, Olchers, T, Peissel, B, Scuvera, G, Zaffaroni, D, Bonanni, B, Feroce, I, Maniscalco, A, Rossi, A, Bernard, L, Tranchant, M, Valois, MF, Turgeon, A, Heguy, L, Yee, PS, Kang, P, Nee, KI, Mariapun, S, Sook-Yee, Y, Lee, D, Ching, TY, Taib, NAM, Otsukka, M, Mononen, K, Selander, T, Weerasooriya, N, Krol-Warmerdam, E, Molenaar, J, Blom, J, Szeszenia-Dabrowska, N, Peplonska, B, Zatonski, W, Chao, P, Stagner, M, Bos, P, Blom, J, Crepin, E, Nieuwlaat, A, Heemskerk, A, Higham, S, Cramp, H, Connley, D, Balasubramanian, S, Brock, I, Kerin, M, Miller, N, Kerbrat, P, Arveux, P, Le Scodan, R, Raoul, Y, Laurent-Puig, P, Mulot, C, Stegmaier, C, Butterbach, K, Karstens, JH, Flesch-Janys, D, Seibold, P, Vrieling, A, Nickels, S, Radice, P, Pylkäs, K, Jukkola-Vuorinen, A, Kauppila, S, Conroy, D, Baynes, C, Chua, K & Pilarski, R 2015, 'Fine-scale mapping of the 4q24 locus identifies & pr two Independent loci associated with breast cancer risk', Cancer Epidemiology Biomarkers and Prevention, vol. 24, no. 11, pp. 1680-1691. https://doi.org/10.1158/1055-9965.EPI-15-0363
Guo, Xingyi ; Long, Jirong ; Zeng, Chenjie ; Michailidou, Kyriaki ; Ghoussaini, Maya ; Bolla, Manjeet K. ; Wang, Qin ; Milne, Roger L. ; Shu, Xiao Ou ; Cai, Qiuyin ; Beesley, Jonathan ; Kar, Siddhartha P. ; Andrulis, Irene L. ; Anton-Culver, Hoda ; Arndt, Volker ; Beckmann, Matthias W. ; Beeghly-Fadiel, Alicia ; Benitez, Javier ; Blot, William ; Bogdanova, Natalia ; Bojesen, Stig E. ; Brauch, Hiltrud ; Brenner, Hermann ; Brinton, Louise ; Broekss, Annegien ; Bruning, Thomas ; Burwinkel, Barbara ; Cai, Hui ; Canisius, Sander ; Chang-Claude, Jenny ; Choi, Ji Yeob ; Couch, Fergus J. ; Cox, Angela ; Cross, Simon S. ; Czene, Kamila ; Darabi, Hatef ; Devilee, Peter ; Droit, Arnaud ; Dork, Thilo ; Fasching, Peter A. ; Fletcher, Olivia ; Flyger, Henrik ; Fostira, Florentia ; Gaborieau, Valerie ; García-Closas, Montserrat ; Giles, Graham G. ; Grip, Mervi ; Guenel, Pascal ; Haiman, Christopher A. ; Hamann, Ute ; Hartman, Mikael ; Hollestelle, Antoinette ; Hopper, John L. ; Hsiung, Chia Ni ; Ito, Hidemi ; Jakubowska, Anna ; Johnson, Nichola ; Kabisch, Maria ; Kang, Daehee ; Khan, Sofia ; Knight, Julia A. ; Kosma, Veli Matti ; Lambrechts, Diether ; Le Marchand, Loic ; Li, Jingmei ; Lindblom, Annika ; Lophatananon, Artitaya ; Lubinski, Jan ; Mannermaa, Arto ; Manoukian, Siranoush ; Margolin, Sara ; Marme, Frederik ; Matsuo, Keitaro ; McLean, Catriona A. ; Meindl, Alfons ; Muir, Kenneth ; Neuhausen, Susan L. ; Nevanlinna, Heli ; Nord, Silje ; Olson, Janet E. ; Orr, Nick ; Peterlongo, Paolo ; Putti, Thomas Choudary ; Rudolph, Anja ; Sangrajrang, Suleeporn ; Sawyer, Elinor J. ; Schmidt, Marjanka K. ; Schmutzler, Rita K. ; Shen, Chen Yang ; Shi, Jiajun ; Shrubsole, Martha J. ; Southey, Melissa C. ; Swerdlow, Anthony ; Teo, Soo Hwang ; Thienpont, Bernard ; Toland, Amanda Ewart ; Tollenaar, Robert A E M ; Tomlinson, Ian P M ; Truong, Therese ; Tseng, Chiu Chen ; Van Den Ouweland, Ans ; Wen, Wanqing ; Winqvist, Robert ; Wu, Anna ; Yip, Cheng Har ; Zamora, M. Pilar ; Zheng, Ying ; Hall, Per ; Pharoah, Paul D P ; Simard, Jacques ; Chenevix-Trench, Georgia ; Dunning, Alison M. ; Easton, Douglas F. ; Zheng, Wei ; Eeles, Rosalind A. ; Al Olama, Ali Amin ; Kote-Jarai, Zsofia ; Benlloch, Sara ; Antoniou, Antonis ; McGuffog, Lesley ; Offit, Ken ; Lee, Andrew ; Dicks, Ed ; Luccarini, Craig ; Tessier, Daniel C. ; Bacot, Francois ; Vincent, Daniel ; La Boissière, Sylvie ; Robidoux, Frederic ; Nielsen, Sune F. ; Cunningham, Julie M. ; Windebank, Sharon A. ; Hilker, Christopher A. ; Meyer, Jeffrey ; Angelakos, Maggie ; Maskiell, Judi ; Van Der Schoot, Ellen ; Rutgers, Emiel ; Verhoef, Senno ; Hogervorst, Frans ; Boonyawongviroj, Prat ; Siriwanarungsan, Pornthep ; Schrauder, Michael ; Rübner, Matthias ; Oeser, Sonja ; Landrith, Silke ; Williams, Eileen ; Ryder-Mills, Elaine ; Sargus, Kara ; McInerney, Niall ; Colleran, Gabrielle ; Rowan, Andrew ; Jones, Angela ; Sohn, Christof ; Schneeweiß, Andeas ; Bugert, Peter ; Álvarez, Núria ; Bernstein, Leslie ; Lacey, James ; Wang, Sophia ; Ma, Huiyan ; Lu, Yani ; Clague De Hart, Jessica ; Deapen, Dennis ; Pinder, Rich ; Lee, Eunjung ; Schumacher, Fred ; Horn-Ross, Pam ; Reynolds, Peggy ; Nelson, David ; Park, Hannah ; Ziegler, Hartwig ; Wolf, Sonja ; Hermann, Volker ; Lo, Wing Yee ; Justenhoven, Christina ; Ko, Yon Dschun ; Baisch, Christian ; Fischer, Hans Peter ; Pesch, Beate ; Rabstein, Sylvia ; Lotz, Anne ; Harth, Volker ; Heikkinen, Tuomas ; Erkkilä, Irja ; Aaltonen, Kirsimari ; Von Smitten, Karl ; Antonenkova, Natalia ; Hillemanns, Peter ; Christiansen, Hans ; Myöhänen, Eija ; Kemiläinen, Helena ; Thorne, Heather ; Niedermayr, Eveline ; Bowtell, D. ; Chenevix-Trench, G. ; De Fazio, A. ; Gertig, D. ; Green, A. ; Webb, P. ; Green, A. ; Parsons, P. ; Hayward, N. ; Webb, P. ; Whiteman, D. ; Fung, Annie ; Yashiki, June ; Peuteman, Gilian ; Smeets, Dominiek ; Van Brussel, Thomas ; Corthouts, Kathleen ; Obi, Nadia ; Heinz, Judith ; Behrens, Sabine ; Eilber, Ursula ; Celik, Muhabbet ; Olchers, Til ; Peissel, Bernard ; Scuvera, Giulietta ; Zaffaroni, Daniela ; Bonanni, Bernardo ; Feroce, Irene ; Maniscalco, Angela ; Rossi, Alessandra ; Bernard, Loris ; Tranchant, Martine ; Valois, Marie France ; Turgeon, Annie ; Heguy, Lea ; Yee, Phuah Sze ; Kang, Peter ; Nee, Kang In ; Mariapun, Shivaani ; Sook-Yee, Yoon ; Lee, Daphne ; Ching, Teh Yew ; Taib, Nur Aishah Mohd ; Otsukka, Meeri ; Mononen, Kari ; Selander, Teresa ; Weerasooriya, Nayana ; Krol-Warmerdam, E. ; Molenaar, J. ; Blom, J. ; Szeszenia-Dabrowska, Neonila ; Peplonska, Beata ; Zatonski, Witold ; Chao, Pei ; Stagner, Michael ; Bos, Petra ; Blom, Jannet ; Crepin, Ellen ; Nieuwlaat, Anja ; Heemskerk, Annette ; Higham, Sue ; Cramp, Helen ; Connley, Dan ; Balasubramanian, Sabapathy ; Brock, Ian ; Kerin, Michael ; Miller, Nicola ; Kerbrat, Pierre ; Arveux, Patrick ; Le Scodan, Romuald ; Raoul, Yves ; Laurent-Puig, Pierre ; Mulot, Claire ; Stegmaier, Christa ; Butterbach, Katja ; Karstens, Johann H. ; Flesch-Janys, Dieter ; Seibold, Petra ; Vrieling, Alina ; Nickels, Stefan ; Radice, Paolo ; Pylkäs, Katri ; Jukkola-Vuorinen, Arja ; Kauppila, Saila ; Conroy, Don ; Baynes, Caroline ; Chua, Kimberley ; Pilarski, Robert. / Fine-scale mapping of the 4q24 locus identifies & pr two Independent loci associated with breast cancer risk. In: Cancer Epidemiology Biomarkers and Prevention. 2015 ; Vol. 24, No. 11. pp. 1680-1691.
@article{2c5721f214a247edb671c49d3b23e9b4,
title = "Fine-scale mapping of the 4q24 locus identifies & pr two Independent loci associated with breast cancer risk",
abstract = "Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P=2.51 × 10-4; OR, 1.04; 95{\%} confidence interval (CI), 1.02-1.07] and rs77928427 (P=1.86 × 10-4; OR, 1.04; 95{\%} CI, 1.02-1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor-binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk.",
author = "Xingyi Guo and Jirong Long and Chenjie Zeng and Kyriaki Michailidou and Maya Ghoussaini and Bolla, {Manjeet K.} and Qin Wang and Milne, {Roger L.} and Shu, {Xiao Ou} and Qiuyin Cai and Jonathan Beesley and Kar, {Siddhartha P.} and Andrulis, {Irene L.} and Hoda Anton-Culver and Volker Arndt and Beckmann, {Matthias W.} and Alicia Beeghly-Fadiel and Javier Benitez and William Blot and Natalia Bogdanova and Bojesen, {Stig E.} and Hiltrud Brauch and Hermann Brenner and Louise Brinton and Annegien Broekss and Thomas Bruning and Barbara Burwinkel and Hui Cai and Sander Canisius and Jenny Chang-Claude and Choi, {Ji Yeob} and Couch, {Fergus J.} and Angela Cox and Cross, {Simon S.} and Kamila Czene and Hatef Darabi and Peter Devilee and Arnaud Droit and Thilo Dork and Fasching, {Peter A.} and Olivia Fletcher and Henrik Flyger and Florentia Fostira and Valerie Gaborieau and Montserrat Garc{\'i}a-Closas and Giles, {Graham G.} and Mervi Grip and Pascal Guenel and Haiman, {Christopher A.} and Ute Hamann and Mikael Hartman and Antoinette Hollestelle and Hopper, {John L.} and Hsiung, {Chia Ni} and Hidemi Ito and Anna Jakubowska and Nichola Johnson and Maria Kabisch and Daehee Kang and Sofia Khan and Knight, {Julia A.} and Kosma, {Veli Matti} and Diether Lambrechts and {Le Marchand}, Loic and Jingmei Li and Annika Lindblom and Artitaya Lophatananon and Jan Lubinski and Arto Mannermaa and Siranoush Manoukian and Sara Margolin and Frederik Marme and Keitaro Matsuo and McLean, {Catriona A.} and Alfons Meindl and Kenneth Muir and Neuhausen, {Susan L.} and Heli Nevanlinna and Silje Nord and Olson, {Janet E.} and Nick Orr and Paolo Peterlongo and Putti, {Thomas Choudary} and Anja Rudolph and Suleeporn Sangrajrang and Sawyer, {Elinor J.} and Schmidt, {Marjanka K.} and Schmutzler, {Rita K.} and Shen, {Chen Yang} and Jiajun Shi and Shrubsole, {Martha J.} and Southey, {Melissa C.} and Anthony Swerdlow and Teo, {Soo Hwang} and Bernard Thienpont and Toland, {Amanda Ewart} and Tollenaar, {Robert A E M} and Tomlinson, {Ian P M} and Therese Truong and Tseng, {Chiu Chen} and {Van Den Ouweland}, Ans and Wanqing Wen and Robert Winqvist and Anna Wu and Yip, {Cheng Har} and Zamora, {M. Pilar} and Ying Zheng and Per Hall and Pharoah, {Paul D P} and Jacques Simard and Georgia Chenevix-Trench and Dunning, {Alison M.} and Easton, {Douglas F.} and Wei Zheng and Eeles, {Rosalind A.} and {Al Olama}, {Ali Amin} and Zsofia Kote-Jarai and Sara Benlloch and Antonis Antoniou and Lesley McGuffog and Ken Offit and Andrew Lee and Ed Dicks and Craig Luccarini and Tessier, {Daniel C.} and Francois Bacot and Daniel Vincent and {La Boissi{\`e}re}, Sylvie and Frederic Robidoux and Nielsen, {Sune F.} and Cunningham, {Julie M.} and Windebank, {Sharon A.} and Hilker, {Christopher A.} and Jeffrey Meyer and Maggie Angelakos and Judi Maskiell and {Van Der Schoot}, Ellen and Emiel Rutgers and Senno Verhoef and Frans Hogervorst and Prat Boonyawongviroj and Pornthep Siriwanarungsan and Michael Schrauder and Matthias R{\"u}bner and Sonja Oeser and Silke Landrith and Eileen Williams and Elaine Ryder-Mills and Kara Sargus and Niall McInerney and Gabrielle Colleran and Andrew Rowan and Angela Jones and Christof Sohn and Andeas Schneewei{\ss} and Peter Bugert and N{\'u}ria {\'A}lvarez and Leslie Bernstein and James Lacey and Sophia Wang and Huiyan Ma and Yani Lu and {Clague De Hart}, Jessica and Dennis Deapen and Rich Pinder and Eunjung Lee and Fred Schumacher and Pam Horn-Ross and Peggy Reynolds and David Nelson and Hannah Park and Hartwig Ziegler and Sonja Wolf and Volker Hermann and Lo, {Wing Yee} and Christina Justenhoven and Ko, {Yon Dschun} and Christian Baisch and Fischer, {Hans Peter} and Beate Pesch and Sylvia Rabstein and Anne Lotz and Volker Harth and Tuomas Heikkinen and Irja Erkkil{\"a} and Kirsimari Aaltonen and {Von Smitten}, Karl and Natalia Antonenkova and Peter Hillemanns and Hans Christiansen and Eija My{\"o}h{\"a}nen and Helena Kemil{\"a}inen and Heather Thorne and Eveline Niedermayr and D. Bowtell and G. Chenevix-Trench and {De Fazio}, A. and D. Gertig and A. Green and P. Webb and A. Green and P. Parsons and N. Hayward and P. Webb and D. Whiteman and Annie Fung and June Yashiki and Gilian Peuteman and Dominiek Smeets and {Van Brussel}, Thomas and Kathleen Corthouts and Nadia Obi and Judith Heinz and Sabine Behrens and Ursula Eilber and Muhabbet Celik and Til Olchers and Bernard Peissel and Giulietta Scuvera and Daniela Zaffaroni and Bernardo Bonanni and Irene Feroce and Angela Maniscalco and Alessandra Rossi and Loris Bernard and Martine Tranchant and Valois, {Marie France} and Annie Turgeon and Lea Heguy and Yee, {Phuah Sze} and Peter Kang and Nee, {Kang In} and Shivaani Mariapun and Yoon Sook-Yee and Daphne Lee and Ching, {Teh Yew} and Taib, {Nur Aishah Mohd} and Meeri Otsukka and Kari Mononen and Teresa Selander and Nayana Weerasooriya and E. Krol-Warmerdam and J. Molenaar and J. Blom and Neonila Szeszenia-Dabrowska and Beata Peplonska and Witold Zatonski and Pei Chao and Michael Stagner and Petra Bos and Jannet Blom and Ellen Crepin and Anja Nieuwlaat and Annette Heemskerk and Sue Higham and Helen Cramp and Dan Connley and Sabapathy Balasubramanian and Ian Brock and Michael Kerin and Nicola Miller and Pierre Kerbrat and Patrick Arveux and {Le Scodan}, Romuald and Yves Raoul and Pierre Laurent-Puig and Claire Mulot and Christa Stegmaier and Katja Butterbach and Karstens, {Johann H.} and Dieter Flesch-Janys and Petra Seibold and Alina Vrieling and Stefan Nickels and Paolo Radice and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Saila Kauppila and Don Conroy and Caroline Baynes and Kimberley Chua and Robert Pilarski",
year = "2015",
month = "11",
day = "1",
doi = "10.1158/1055-9965.EPI-15-0363",
language = "English",
volume = "24",
pages = "1680--1691",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

TY - JOUR

T1 - Fine-scale mapping of the 4q24 locus identifies & pr two Independent loci associated with breast cancer risk

AU - Guo, Xingyi

AU - Long, Jirong

AU - Zeng, Chenjie

AU - Michailidou, Kyriaki

AU - Ghoussaini, Maya

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Milne, Roger L.

AU - Shu, Xiao Ou

AU - Cai, Qiuyin

AU - Beesley, Jonathan

AU - Kar, Siddhartha P.

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Arndt, Volker

AU - Beckmann, Matthias W.

AU - Beeghly-Fadiel, Alicia

AU - Benitez, Javier

AU - Blot, William

AU - Bogdanova, Natalia

AU - Bojesen, Stig E.

AU - Brauch, Hiltrud

AU - Brenner, Hermann

AU - Brinton, Louise

AU - Broekss, Annegien

AU - Bruning, Thomas

AU - Burwinkel, Barbara

AU - Cai, Hui

AU - Canisius, Sander

AU - Chang-Claude, Jenny

AU - Choi, Ji Yeob

AU - Couch, Fergus J.

AU - Cox, Angela

AU - Cross, Simon S.

AU - Czene, Kamila

AU - Darabi, Hatef

AU - Devilee, Peter

AU - Droit, Arnaud

AU - Dork, Thilo

AU - Fasching, Peter A.

AU - Fletcher, Olivia

AU - Flyger, Henrik

AU - Fostira, Florentia

AU - Gaborieau, Valerie

AU - García-Closas, Montserrat

AU - Giles, Graham G.

AU - Grip, Mervi

AU - Guenel, Pascal

AU - Haiman, Christopher A.

AU - Hamann, Ute

AU - Hartman, Mikael

AU - Hollestelle, Antoinette

AU - Hopper, John L.

AU - Hsiung, Chia Ni

AU - Ito, Hidemi

AU - Jakubowska, Anna

AU - Johnson, Nichola

AU - Kabisch, Maria

AU - Kang, Daehee

AU - Khan, Sofia

AU - Knight, Julia A.

AU - Kosma, Veli Matti

AU - Lambrechts, Diether

AU - Le Marchand, Loic

AU - Li, Jingmei

AU - Lindblom, Annika

AU - Lophatananon, Artitaya

AU - Lubinski, Jan

AU - Mannermaa, Arto

AU - Manoukian, Siranoush

AU - Margolin, Sara

AU - Marme, Frederik

AU - Matsuo, Keitaro

AU - McLean, Catriona A.

AU - Meindl, Alfons

AU - Muir, Kenneth

AU - Neuhausen, Susan L.

AU - Nevanlinna, Heli

AU - Nord, Silje

AU - Olson, Janet E.

AU - Orr, Nick

AU - Peterlongo, Paolo

AU - Putti, Thomas Choudary

AU - Rudolph, Anja

AU - Sangrajrang, Suleeporn

AU - Sawyer, Elinor J.

AU - Schmidt, Marjanka K.

AU - Schmutzler, Rita K.

AU - Shen, Chen Yang

AU - Shi, Jiajun

AU - Shrubsole, Martha J.

AU - Southey, Melissa C.

AU - Swerdlow, Anthony

AU - Teo, Soo Hwang

AU - Thienpont, Bernard

AU - Toland, Amanda Ewart

AU - Tollenaar, Robert A E M

AU - Tomlinson, Ian P M

AU - Truong, Therese

AU - Tseng, Chiu Chen

AU - Van Den Ouweland, Ans

AU - Wen, Wanqing

AU - Winqvist, Robert

AU - Wu, Anna

AU - Yip, Cheng Har

AU - Zamora, M. Pilar

AU - Zheng, Ying

AU - Hall, Per

AU - Pharoah, Paul D P

AU - Simard, Jacques

AU - Chenevix-Trench, Georgia

AU - Dunning, Alison M.

AU - Easton, Douglas F.

AU - Zheng, Wei

AU - Eeles, Rosalind A.

AU - Al Olama, Ali Amin

AU - Kote-Jarai, Zsofia

AU - Benlloch, Sara

AU - Antoniou, Antonis

AU - McGuffog, Lesley

AU - Offit, Ken

AU - Lee, Andrew

AU - Dicks, Ed

AU - Luccarini, Craig

AU - Tessier, Daniel C.

AU - Bacot, Francois

AU - Vincent, Daniel

AU - La Boissière, Sylvie

AU - Robidoux, Frederic

AU - Nielsen, Sune F.

AU - Cunningham, Julie M.

AU - Windebank, Sharon A.

AU - Hilker, Christopher A.

AU - Meyer, Jeffrey

AU - Angelakos, Maggie

AU - Maskiell, Judi

AU - Van Der Schoot, Ellen

AU - Rutgers, Emiel

AU - Verhoef, Senno

AU - Hogervorst, Frans

AU - Boonyawongviroj, Prat

AU - Siriwanarungsan, Pornthep

AU - Schrauder, Michael

AU - Rübner, Matthias

AU - Oeser, Sonja

AU - Landrith, Silke

AU - Williams, Eileen

AU - Ryder-Mills, Elaine

AU - Sargus, Kara

AU - McInerney, Niall

AU - Colleran, Gabrielle

AU - Rowan, Andrew

AU - Jones, Angela

AU - Sohn, Christof

AU - Schneeweiß, Andeas

AU - Bugert, Peter

AU - Álvarez, Núria

AU - Bernstein, Leslie

AU - Lacey, James

AU - Wang, Sophia

AU - Ma, Huiyan

AU - Lu, Yani

AU - Clague De Hart, Jessica

AU - Deapen, Dennis

AU - Pinder, Rich

AU - Lee, Eunjung

AU - Schumacher, Fred

AU - Horn-Ross, Pam

AU - Reynolds, Peggy

AU - Nelson, David

AU - Park, Hannah

AU - Ziegler, Hartwig

AU - Wolf, Sonja

AU - Hermann, Volker

AU - Lo, Wing Yee

AU - Justenhoven, Christina

AU - Ko, Yon Dschun

AU - Baisch, Christian

AU - Fischer, Hans Peter

AU - Pesch, Beate

AU - Rabstein, Sylvia

AU - Lotz, Anne

AU - Harth, Volker

AU - Heikkinen, Tuomas

AU - Erkkilä, Irja

AU - Aaltonen, Kirsimari

AU - Von Smitten, Karl

AU - Antonenkova, Natalia

AU - Hillemanns, Peter

AU - Christiansen, Hans

AU - Myöhänen, Eija

AU - Kemiläinen, Helena

AU - Thorne, Heather

AU - Niedermayr, Eveline

AU - Bowtell, D.

AU - Chenevix-Trench, G.

AU - De Fazio, A.

AU - Gertig, D.

AU - Green, A.

AU - Webb, P.

AU - Green, A.

AU - Parsons, P.

AU - Hayward, N.

AU - Webb, P.

AU - Whiteman, D.

AU - Fung, Annie

AU - Yashiki, June

AU - Peuteman, Gilian

AU - Smeets, Dominiek

AU - Van Brussel, Thomas

AU - Corthouts, Kathleen

AU - Obi, Nadia

AU - Heinz, Judith

AU - Behrens, Sabine

AU - Eilber, Ursula

AU - Celik, Muhabbet

AU - Olchers, Til

AU - Peissel, Bernard

AU - Scuvera, Giulietta

AU - Zaffaroni, Daniela

AU - Bonanni, Bernardo

AU - Feroce, Irene

AU - Maniscalco, Angela

AU - Rossi, Alessandra

AU - Bernard, Loris

AU - Tranchant, Martine

AU - Valois, Marie France

AU - Turgeon, Annie

AU - Heguy, Lea

AU - Yee, Phuah Sze

AU - Kang, Peter

AU - Nee, Kang In

AU - Mariapun, Shivaani

AU - Sook-Yee, Yoon

AU - Lee, Daphne

AU - Ching, Teh Yew

AU - Taib, Nur Aishah Mohd

AU - Otsukka, Meeri

AU - Mononen, Kari

AU - Selander, Teresa

AU - Weerasooriya, Nayana

AU - Krol-Warmerdam, E.

AU - Molenaar, J.

AU - Blom, J.

AU - Szeszenia-Dabrowska, Neonila

AU - Peplonska, Beata

AU - Zatonski, Witold

AU - Chao, Pei

AU - Stagner, Michael

AU - Bos, Petra

AU - Blom, Jannet

AU - Crepin, Ellen

AU - Nieuwlaat, Anja

AU - Heemskerk, Annette

AU - Higham, Sue

AU - Cramp, Helen

AU - Connley, Dan

AU - Balasubramanian, Sabapathy

AU - Brock, Ian

AU - Kerin, Michael

AU - Miller, Nicola

AU - Kerbrat, Pierre

AU - Arveux, Patrick

AU - Le Scodan, Romuald

AU - Raoul, Yves

AU - Laurent-Puig, Pierre

AU - Mulot, Claire

AU - Stegmaier, Christa

AU - Butterbach, Katja

AU - Karstens, Johann H.

AU - Flesch-Janys, Dieter

AU - Seibold, Petra

AU - Vrieling, Alina

AU - Nickels, Stefan

AU - Radice, Paolo

AU - Pylkäs, Katri

AU - Jukkola-Vuorinen, Arja

AU - Kauppila, Saila

AU - Conroy, Don

AU - Baynes, Caroline

AU - Chua, Kimberley

AU - Pilarski, Robert

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P=2.51 × 10-4; OR, 1.04; 95% confidence interval (CI), 1.02-1.07] and rs77928427 (P=1.86 × 10-4; OR, 1.04; 95% CI, 1.02-1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor-binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk.

AB - Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P=2.51 × 10-4; OR, 1.04; 95% confidence interval (CI), 1.02-1.07] and rs77928427 (P=1.86 × 10-4; OR, 1.04; 95% CI, 1.02-1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor-binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk.

UR - http://www.scopus.com/inward/record.url?scp=84946544208&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84946544208&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-15-0363

DO - 10.1158/1055-9965.EPI-15-0363

M3 - Article

AN - SCOPUS:84946544208

VL - 24

SP - 1680

EP - 1691

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 11

ER -