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https://doi.org/10.1186/s13058-016-0718-0
| Title: | Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus | Authors: | Zeng, Chenjie Guo, Xingyi Long, Jirong Kuchenbaecker, Karoline B Droit, Arnaud Michailidou, Kyriaki Ghoussaini, Maya Kar, Siddhartha Freeman, Adam Hopper, John L Milne, Roger L Bolla, Manjeet K Wang, Qin Dennis, Joe Agata, Simona Ahmed, Shahana Aittomaki, Kristiina Andrulis, Irene L Anton-Culver, Hoda Antonenkova, Natalia N Arason, Adalgeir Arndt, Volker Arun, Banu K Arver, Brita Bacot, Francois Barrowdale, Daniel Baynes, Caroline Beeghly-Fadiel, Alicia Benitez, Javier Bermisheva, Marina Blomqvist, Carl Blot, William J Bogdanova, Natalia V Bojesen, Stig E Bonanni, Bernardo Borresen-Dale, Anne-Lise Brand, Judith S Brauch, Hiltrud Brennan, Paul Brenner, Hermann Broeks, Annegien Bruening, Thomas Burwinkel, Barbara Buys, Saundra S Cai, Qiuyin Caldes, Trinidad Campbell, Ian Carpenter, Jane Chang-Claude, Jenny Choi, Ji-Yeob Claes, Kathleen BM Clarke, Christine Cox, Angela Cross, Simon S Czene, Kamila Daly, Mary B de la Hoya, Miguel De Leeneer, Kim Devilee, Peter Diez, Orland Domchek, Susan M Doody, Michele Dorfling, Cecilia M Doerk, Thilo dos-Santos-Silva, Isabel Dumont, Martine Dwek, Miriam Dworniczak, Bernd Egan, Kathleen Eilber, Ursula Einbeigi, Zakaria Ejlertsen, Bent Ellis, Steve Frost, Debra Lalloo, Fiona Fasching, Peter A Figueroa, Jonine Flyger, Henrik Friedlander, Michael Friedman, Eitan Gambino, Gaetana Gao, Yu-Tang Garber, Judy Garcia-Closas, Montserrat Gehrig, Andrea Damiola, Francesca Lesueur, Fabienne Mazoyer, Sylvie Stoppa-Lyonnet, Dominique Giles, Graham G Godwin, Andrew K Goldgar, David E Gonzalez-Neira, Anna Greene, Mark H Guenel, Pascal Haeberle, Lothar Haiman, Christopher A Hallberg, Emily Hamann, Ute Hansen, Thomas VO Hart, Steven Hartikainen, Jaana M Hartman, Mikael Hassan, Norhashimah Healey, Sue Hogervorst, Frans BL Verhoef, Senno Hendricks, Carolyn B Hillemanns, Peter Hollestelle, Antoinette Hulick, Peter J Hunter, David J Imyanitov, Evgeny N Isaacs, Claudine Ito, Hidemi Jakubowska, Anna Janavicius, Ramunas Jaworska-Bieniek, Katarzyna Jensen, Uffe Birk John, Esther M Beauparlant, Charles Joly Jones, Michael Kabisch, Maria Kang, Daehee Karlan, Beth Y Kauppila, Saila Kerin, Michael J Khan, Sofia Khusnutdinova, Elza Knight, Julia A Konstantopoulou, Irene Kraft, Peter Kwong, Ava Laitman, Yael Lambrechts, Diether Lazaro, Conxi Le Marchand, Loic Lee, Chuen Neng Lee, Min Hyuk Lester, Jenny Li, Jingmei Liljegren, Annelie Lindblom, Annika Lophatananon, Artitaya Lubinski, Jan Mai, Phuong L Mannermaa, Arto Manoukian, Siranoush Margolin, Sara Marme, Frederik Matsuo, Keitaro McGuffog, Lesley Meindl, Alfons Menegaux, Florence Montagna, Marco Muir, Kenneth Mulligan, Anna Marie Nathanson, Katherine L Neuhausen, Susan L Nevanlinna, Heli Newcomb, Polly A Nord, Silje Nussbaum, Robert L Offit, Kenneth Olah, Edith Olopade, Olufunmilayo I Olswold, Curtis Osorio, Ana Papi, Laura Park-Simon, Tjoung-Won Paulsson-Karlsson, Ylva Peeters, Stephanie Peissel, Bernard Peterlongo, Paolo Peto, Julian Pfeiler, Georg Phelan, Catherine M Presneau, Nadege Radice, Paolo Rahman, Nazneen Ramus, Susan J Rashid, Muhammad Usman Rennert, Gad Rhiem, Kerstin Rudolph, Anja Salani, Ritu Sangrajrang, Suleeporn Sawyer, Elinor J Schmidt, Marjanka K Schmutzler, Rita K Schoemaker, Minouk J Schuermann, Peter Seynaeve, Caroline Shen, Chen-Yang Shrubsole, Martha J Shu, Xiao-Ou Sigurdson, Alice Singer, Christian F Slager, Susan Soucy, Penny Southey, Melissa Steinemann, Doris Swerdlow, Anthony Szabo, Csilla I Tchatchou, Sandrine Teixeira, Manuel R Teo, Soo H Terry, Mary Beth Tessier, Daniel C Teule, Alex Thomassen, Mads Tihomirova, Laima Tischkowitz, Marc Toland, Amanda E Tung, Nadine Turnbull, Clare van den Ouweland, Ans MW van Rensburg, Elizabeth J ven den Berg, David Vijai, Joseph Wang-Gohrke, Shan Weitzel, Jeffrey N Whittemore, Alice S Winqvist, Robert Wong, Tien Y Wu, Anna H Yannoukakos, Drakoulis Yu, Jyh-Cherng Pharoah, Paul DP Hall, Per Chenevix-Trench, Georgia Dunning, Alison M Simard, Jacques Couch, Fergus J Antoniou, Antonis C Easton, Douglas F Zheng, Wei |
Keywords: | Science & Technology Life Sciences & Biomedicine Oncology Fine-scale mapping Genetic risk factor PTHLH CCDC91 Breast cancer BRAC1 mutation carriers HORMONE-RELATED PROTEIN GENOME-WIDE ASSOCIATION BRCA2 MUTATION CARRIERS LOCALIZATION MODIFIERS IDENTIFY GENES MICE |
Issue Date: | 21-Jun-2016 | Publisher: | BMC | Citation: | Zeng, Chenjie, Guo, Xingyi, Long, Jirong, Kuchenbaecker, Karoline B, Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Kar, Siddhartha, Freeman, Adam, Hopper, John L, Milne, Roger L, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Agata, Simona, Ahmed, Shahana, Aittomaki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arason, Adalgeir, Arndt, Volker, Arun, Banu K, Arver, Brita, Bacot, Francois, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William J, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brand, Judith S, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S, Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Choi, Ji-Yeob, Claes, Kathleen BM, Clarke, Christine, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, de la Hoya, Miguel, De Leeneer, Kim, Devilee, Peter, Diez, Orland, Domchek, Susan M, Doody, Michele, Dorfling, Cecilia M, Doerk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter A, Figueroa, Jonine, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Gao, Yu-Tang, Garber, Judy, Garcia-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham G, Godwin, Andrew K, Goldgar, David E, Gonzalez-Neira, Anna, Greene, Mark H, Guenel, Pascal, Haeberle, Lothar, Haiman, Christopher A, Hallberg, Emily, Hamann, Ute, Hansen, Thomas VO, Hart, Steven, Hartikainen, Jaana M, Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Hogervorst, Frans BL, Verhoef, Senno, Hendricks, Carolyn B, Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter J, Hunter, David J, Imyanitov, Evgeny N, Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, Jensen, Uffe Birk, John, Esther M, Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Kang, Daehee, Karlan, Beth Y, Kauppila, Saila, Kerin, Michael J, Khan, Sofia, Khusnutdinova, Elza, Knight, Julia A, Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Lazaro, Conxi, Le Marchand, Loic, Lee, Chuen Neng, Lee, Min Hyuk, Lester, Jenny, Li, Jingmei, Liljegren, Annelie, Lindblom, Annika, Lophatananon, Artitaya, Lubinski, Jan, Mai, Phuong L, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Matsuo, Keitaro, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L, Neuhausen, Susan L, Nevanlinna, Heli, Newcomb, Polly A, Nord, Silje, Nussbaum, Robert L, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I, Olswold, Curtis, Osorio, Ana, Papi, Laura, Park-Simon, Tjoung-Won, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine M, Presneau, Nadege, Radice, Paolo, Rahman, Nazneen, Ramus, Susan J, Rashid, Muhammad Usman, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Sangrajrang, Suleeporn, Sawyer, Elinor J, Schmidt, Marjanka K, Schmutzler, Rita K, Schoemaker, Minouk J, Schuermann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha J, Shu, Xiao-Ou, Sigurdson, Alice, Singer, Christian F, Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla I, Tchatchou, Sandrine, Teixeira, Manuel R, Teo, Soo H, Terry, Mary Beth, Tessier, Daniel C, Teule, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda E, Tung, Nadine, Turnbull, Clare, van den Ouweland, Ans MW, van Rensburg, Elizabeth J, ven den Berg, David, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey N, Whittemore, Alice S, Winqvist, Robert, Wong, Tien Y, Wu, Anna H, Yannoukakos, Drakoulis, Yu, Jyh-Cherng, Pharoah, Paul DP, Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison M, Simard, Jacques, Couch, Fergus J, Antoniou, Antonis C, Easton, Douglas F, Zheng, Wei (2016-06-21). Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus. BREAST CANCER RESEARCH 18 (1). ScholarBank@NUS Repository. https://doi.org/10.1186/s13058-016-0718-0 | Abstract: | Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10-9), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10-5), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10-4) identified in the general populations, and rs113824616 (P = 7 × 10-5) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk. | Source Title: | BREAST CANCER RESEARCH | URI: | https://scholarbank.nus.edu.sg/handle/10635/208277 | ISSN: | 14655411 1465542X |
DOI: | 10.1186/s13058-016-0718-0 |
| Appears in Collections: | Staff Publications Elements |
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