Stevens, Kristen N. and Fredericksen, Zachary and Vachon, Celine and Wang , Xianshu and Margolin, Sara and Lindblom, Annika and Nevanlinna, Heli and Greco, Dario and Aittomaki, Kristiina and Blomqvist, Carl and Chang-Claude, Jenny and Vrieling, Alina and Flesch-Janys, Dieter and Sinn, Hans-Peter and Wang-Gohrke, Shan and Nickels, Stefan and Brauch, Hiltrud and Ko, Yon-Dschun and Fischer, Hans-Peter and Schmutzler, Rita K. and Meindl, Alfons and Bartram, Claus R. and Schott, Sarah and Engel, Christoph and Godwin, Andrew K. and Weaver, JoEllen and Pathak, Harsh B. and Sharma, Priyanka and Brenner, Hermann and Muller, Heiko and Arndt, Volker and Stegmaier, Christa and Miron, Penelope and Yannoukakos, Drakoulis and Stavropoulou, Alexandra and Fountzilas, George and Gogas, Helen J. and Swann, Ruth and Dwek, Miriam and Perkins, Annie and Milne, Roger L. and Benitez, Javier and Zamora, M. Pilar and Ignacio Arias Perez, Jose and Bojesen, Stig E. and Nielsen, Sune F. and Nordestgaard, Borge G. and Flyger, Henrik and Guenel, Pascal and Truong, Therese and Menegaux, Florence and Cordina-Duverger, Emilie and Burwinkel, Barbara and Marme, Frederick and Schneeweiss, Andreas and Sohn, Christof and Sawyer, Elinor and Tomlinson, Ian and Kerin, Michael J. and Peto, Julian and Johnson, Nichola and Fletcher, Olivia and Dos Santos Silva, Isabel and Fasching, Peter A. and Beckmann, Matthias W. and Hartmann, Arndt and Ekici, Arif B. and Lophatananon, Artitaya and Muir, Kenneth and Puttawibul, Puttisak and Wiangnon, Surapon and Schmidt, Marjanka K. and Broeks, Annegien and Braaf, Linde M. and Rosenberg, Efraim H. and Hopper, John L. and Apicella, Carmel and Park, Daniel J. and Southey , Melissa C. and Swerdlow, Anthony J. and Ashworth, Alan and Orr, Nick and Schoemaker, Minouk J. and Anton-Culver, Hoda and Ziogas, Argyrios and Bernstein, Leslie and Clarke Dur, Christina and Shen, Chen-Yang and Yu, Jyh-Cherng and Hsu, Huan-Ming and Hsiung, Chia-Ni and Hamann, Ute and Dünnebier, Thomas and Rüdiger, Thomas and Ulmer, Hans Ulrich and Pharoah, Paul D. P. and Dunning, Alison M. and Humphreys, Manjeet K. and Wang, Qin and Cox, Angela and Cross, Simon S. and Reed, Malcolm W.R. and Hall , Per and Czene, Kamila and Ambrosone, Christine B. and Ademuyiwa, Foluso and Hwang, Helena and Eccles, Diana M. and Garcia-Closas, Montserrat and Figueroa, Jonine D. and Sherman, Mark E. and Lissowska, Jolanta and Devilee, Peter and Seynaeve, Caroline and Tollenaar, R.A.E.M and Hooning, Maartje J. and Andrulis, Irene L. and Knight, Julia A. and Glendon, Gord and Mulligan, Anne Marie and Winqvist, Robert and Pylkas, Katri and Jukkola-Vuorinen, Arja and Grip, Mervi and John , Esther M. and Miron, Alexander and Grenaker Alnaes, Grethe and Kristensen, Vessela and Borresen-Dale, Anne-Lise and Giles, Graham G. and Baglietto, Laura and McLean, Catriona A. and Severi, Gianluca and Kose, Matthew L. and Pankratz, V. Shane and Slager, Susan and Olson, Janet E. and Radice, Paolo and Peterlongo, Paolo and Manoukian, Siranoush and Barile, Monica and Lambrechts, Diether and Hatse, Sigrid and Dieudonne, Anne-Sophie and Christiaens, Marie-Rose and Chenevix-Trench, Georgia and Beesley, Jonathan and Chen, Xiaoqing and Mannermaa, Arto and Kosma, Veli-Matti and Hartikainen, Jaana M. and Soini, Ylermi and Easton, Douglas F. and Couch, Fergus J. (2012) 19p13.1 is a triple negative-specific breast cancer susceptibility locus. Cancer Research, 72 (7). pp. 1795-1803. ISSN 0008-5472
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Official URL: http://dx.doi.org/10.1158/0008-5472.CAN-11-3364
The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
|Additional Information:||The GENICA Network, kConFab Investigators and AOCS Group also listed under author|
|Research Community:||University of Westminster > Life Sciences, School of|
|Deposited On:||09 Mar 2012 11:06|
|Last Modified:||27 Aug 2014 12:26|
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