9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium
Background: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). - Methods: To further investigate the rs865686-breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises...
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| Hauptverfasser: | , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
August 2, 2012
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| In: |
Cancer epidemiology, biomarkers & prevention
Year: 2012, Jahrgang: 21, Heft: 10, Pages: 1783-1791 |
| ISSN: | 1538-7755 |
| DOI: | 10.1158/1055-9965.EPI-12-0526 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1158/1055-9965.EPI-12-0526 Verlag, Volltext: http://cebp.aacrjournals.org/content/21/10/1783 
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| Verfasserangaben: | Helen Warren, Frank Dudbridge, Olivia Fletcher, Nick Orr, Nichola Johnson, John L. Hopper, Carmel Apicella, Melissa C. Southey, Maryam Mahmoodi, Marjanka K. Schmidt, Annegien Broeks, Sten Cornelissen, Linda M. Braaf, Kenneth R. Muir, Artitaya Lophatananon, Arkom Chaiwerawattana, Surapon Wiangnon, Peter A. Fasching, Matthias W. Beckmann, Arif B. Ekici, Ruediger Schulz-Wendtland, Elinor J. Sawyer, Ian Tomlinson, Michael Kerin, Barbara Burwinkel, Frederik Marme, Andreas Schneeweiss, Christof Sohn, Pascal Guénel, Thérèse Truong, Pierre Laurent-Puig, Claire Mulot, Stig E. Bojesen, Sune F. Nielsen, Henrik Flyger, Børge G. Nordestgaard, Roger L. Milne, Javier Benítez, José-Ignacio Arias-Pérez, M. Pilar Zamora, Hoda Anton-Culver, Argyrios Ziogas, Leslie Bernstein, Christina Clarke Dur, Hermann Brenner, Heiko Müller, Volker Arndt, Anne Langheinz, Alfons Meindl, Michael Golatta, Claus R. Bartram, Rita K. Schmutzler, Hiltrud Brauch, Christina Justenhoven, Thomas Brüning, for The GENICA Network, Jenny Chang-Claude, Shan Wang-Gohrke, Ursula Eilber, Thilo Dörk, Peter Schürmann, Michael Bremer, Peter Hillemanns, Heli Nevanlinna, Taru A. Muranen, Kristiina Aittomäki, Carl Blomqvist, Natalia Bogdanova, Natalia Antonenkova, Yuriy Rogov, Marina Bermisheva, Darya Prokofyeva, Guzel Zinnatullina, Elza Khusnutdinova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Veli-Matti Kosma, Jaana M. Hartikainen, Vesa Kataja, Georgia Chenevix-Trench, Jonathan Beesley, Xiaoqing Chen, for kConFab Investigators, Australian Ovarian Cancer Study Group, Diether Lambrechts, Ann Smeets, Robert Paridaens, Caroline Weltens, Dieter Flesch-Janys, Katharina Buck, Sabine Behrens, Paolo Peterlongo, Loris Bernard, Siranoush Manoukian, Paolo Radice, Fergus J. Couch, Celine Vachon, Xianshu Wang, Janet Olson, Graham Giles, Laura Baglietto, Cariona A. McLean, Gianluca Severi, Esther M. John, Alexander Miron, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L. Andrulis, Julia A. Knight, Anna Marie Mulligan, Nayana Weerasooriya, Peter Devilee, Robert A. E. M. Tollenaar, John W. M. Martens, Caroline M. Seynaeve, Maartje J. Hooning, Antoinette Hollestelle, Agnes Jager, Madeleine M. A. Tilanus-Linthorst, Per Hall, Kamila Czene, Jianjun Liu, Jingmei Li, Angela Cox, Simon S. Cross, Ian W. Brock, Malcolm W. R. Reed, Paul Pharoah, Fiona M. Blows, Alison M. Dunning, Maya Ghoussaini, Alan Ashworth, Anthony Swerdlow, Michael Jones, Minouk Schoemaker, Douglas F. Easton, Manjeet Humphreys, Qin Wang, Julian Peto, Isabel dos-Santos-Silva |
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| 245 | 1 | 0 | |a 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer |b evidence from the Breast Cancer Association Consortium |c Helen Warren, Frank Dudbridge, Olivia Fletcher, Nick Orr, Nichola Johnson, John L. Hopper, Carmel Apicella, Melissa C. Southey, Maryam Mahmoodi, Marjanka K. Schmidt, Annegien Broeks, Sten Cornelissen, Linda M. Braaf, Kenneth R. Muir, Artitaya Lophatananon, Arkom Chaiwerawattana, Surapon Wiangnon, Peter A. Fasching, Matthias W. Beckmann, Arif B. Ekici, Ruediger Schulz-Wendtland, Elinor J. Sawyer, Ian Tomlinson, Michael Kerin, Barbara Burwinkel, Frederik Marme, Andreas Schneeweiss, Christof Sohn, Pascal Guénel, Thérèse Truong, Pierre Laurent-Puig, Claire Mulot, Stig E. Bojesen, Sune F. Nielsen, Henrik Flyger, Børge G. Nordestgaard, Roger L. Milne, Javier Benítez, José-Ignacio Arias-Pérez, M. Pilar Zamora, Hoda Anton-Culver, Argyrios Ziogas, Leslie Bernstein, Christina Clarke Dur, Hermann Brenner, Heiko Müller, Volker Arndt, Anne Langheinz, Alfons Meindl, Michael Golatta, Claus R. Bartram, Rita K. Schmutzler, Hiltrud Brauch, Christina Justenhoven, Thomas Brüning, for The GENICA Network, Jenny Chang-Claude, Shan Wang-Gohrke, Ursula Eilber, Thilo Dörk, Peter Schürmann, Michael Bremer, Peter Hillemanns, Heli Nevanlinna, Taru A. Muranen, Kristiina Aittomäki, Carl Blomqvist, Natalia Bogdanova, Natalia Antonenkova, Yuriy Rogov, Marina Bermisheva, Darya Prokofyeva, Guzel Zinnatullina, Elza Khusnutdinova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Veli-Matti Kosma, Jaana M. Hartikainen, Vesa Kataja, Georgia Chenevix-Trench, Jonathan Beesley, Xiaoqing Chen, for kConFab Investigators, Australian Ovarian Cancer Study Group, Diether Lambrechts, Ann Smeets, Robert Paridaens, Caroline Weltens, Dieter Flesch-Janys, Katharina Buck, Sabine Behrens, Paolo Peterlongo, Loris Bernard, Siranoush Manoukian, Paolo Radice, Fergus J. Couch, Celine Vachon, Xianshu Wang, Janet Olson, Graham Giles, Laura Baglietto, Cariona A. McLean, Gianluca Severi, Esther M. John, Alexander Miron, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L. Andrulis, Julia A. Knight, Anna Marie Mulligan, Nayana Weerasooriya, Peter Devilee, Robert A. E. M. Tollenaar, John W. M. Martens, Caroline M. Seynaeve, Maartje J. Hooning, Antoinette Hollestelle, Agnes Jager, Madeleine M. A. Tilanus-Linthorst, Per Hall, Kamila Czene, Jianjun Liu, Jingmei Li, Angela Cox, Simon S. Cross, Ian W. Brock, Malcolm W. R. Reed, Paul Pharoah, Fiona M. Blows, Alison M. Dunning, Maya Ghoussaini, Alan Ashworth, Anthony Swerdlow, Michael Jones, Minouk Schoemaker, Douglas F. Easton, Manjeet Humphreys, Qin Wang, Julian Peto, Isabel dos-Santos-Silva |
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| 520 | |a Background: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). - Methods: To further investigate the rs865686-breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case-control studies (48,394 cases, 50,836 controls). - Results: This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P = 2.01 × 10−29] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (Phet) = 1.3 × 10−143], but no evidence of ethnic differences in per allele OR (Phet = 0.43). rs865686 was associated with estrogen receptor-positive (ER+) disease (per G-allele OR, 0.89; 95% CI, 0.86-0.91; P = 3.13 × 10−22) but less strongly, if at all, with ER-negative (ER−) disease (OR, 0.98; 95% CI, 0.94-1.02; P = 0.26; Phet = 1.16 × 10−6), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the G allele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER+ tumors. - Conclusions: This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer. - Impact: The findings further support the view that genetic susceptibility varies according to tumor subtype. Cancer Epidemiol Biomarkers Prev; 21(10); 1783-. ©2012 AACR. | ||
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