Refine
Has Fulltext
- yes (2)
Is part of the Bibliography
- yes (2)
Document Type
- Journal article (2)
Language
- English (2)
Keywords
- cancer (1)
- cell (1)
- chip-seq (1)
- elements (1)
- expression signature (1)
- genetic interaction networks (1)
- genetics (1)
- genome-wide association (1)
- modifiers (1)
- polymorphism (1)
Author
- Dunning, Alison M. (2) (remove)
Institute
Blanco, Ignacio ; Kuchenbaecker, Karoline ; Cuadras, Daniel ; Wang, Xianshu ; Barrowdale, Daniel ; Ruiz de Garibay, Gorka ; Librado, Pablo ; Sanchez-Gracia, Alejandro ; Rozas, Julio ; Bonifaci, Núria ; McGuffog, Lesley ; Pankratz, Vernon S. ; Islam, Abul ; Mateo, Francesca ; Berenguer, Antoni ; Petit, Anna ; Català, Isabel ; Brunet, Joan ; Feliubadaló, Lidia ; Tornero, Eva ; Benítez, Javier ; Osorio, Ana ; Ramón y Cajal, Teresa ; Nevanlinna, Heli ; Aittomäki, Kristina ; Arun, Banu K. ; Toland, Amanda E. ; Karlan, Beth Y. ; Walsh, Christine ; Lester, Jenny ; Greene, Mark H. ; Mai, Phuong L. ; Nussbaum, Robert L. ; Andrulis, Irene L. ; Domchek, Susan M. ; Nathanson, Katherine L. ; Rebbeck, Timothy R. ; Barkardottir, Rosa B. ; Jakubowska, Anna ; Lubinski, Jan ; Durda, Katarzyna ; Jaworska-Bieniek, Katarzyna ; Claes, Kathleen ; Van Maerken, Tom ; Díez, Orland ; Hansen, Thomas V. ; Jønson, Lars ; Gerdes, Anne-Marie ; Ejlertsen, Bent ; De la Hoya, Miguel ; Caldés, Trinidad ; Dunning, Alison M. ; Oliver, Clare ; Fineberg, Elena ; Cook, Margaret ; Peock, Susan ; McCann, Emma ; Murray, Alex ; Jacobs, Chris ; Pichert, Gabriella ; Lalloo, Fiona ; Chu, Carol ; Dorkins, Huw ; Paterson, Joan ; Ong, Kai-Ren ; Teixeira, Manuel R. ; Hogervorst, Frans B. L. ; Van der Hout, Annemarie H. ; Seynaeve, Caroline ; Van der Luijt, Rob B. ; Ligtenberg, Marjolijn J. L. ; Devilee, Peter ; Wijnen, Juul T. ; Rookus, Matti A. ; Meijers-Heijboer, Hanne E. J. ; Blok, Marinus J. ; Van den Ouweland, Ans M. W. ; Aalfs, Cora M. ; Rodriguez, Gustavo C. ; Phillips, Kelly-Anne A. ; Piedmonte, Marion ; Nerenstone, Stacy R. ; Bae-Jump, Victoria L. ; O'Malley, David M. ; Schmutzler, Rita K. ; Wappenschmidt, Barbara ; Rhiem, Kerstin ; Engel, Christoph ; Meindl, Alfons ; Ditsch, Nina ; Arnold, Norbert ; Plendl, Hansjoerg J. ; Niederacher, Dieter ; Sutter, Christian ; Wang-Gohrke, Shan ; Steinemann, Doris ; Preisler-Adams, Sabine ; Kast, Karin ; Varon-Mateeva, Raymonda ; Gehrig, Andrea ; Bojesen, Anders ; Pedersen, Inge Sokilde ; Sunde, Lone ; Birk Jensen, Uffe ; Thomassen, Mads ; Kruse, Torben A. ; Foretova, Lenka ; Peterlongo, Paolo ; Bernard, Loris ; Peissel, Bernard ; Scuvera, Giulietta ; Manoukian, Siranoush ; Radice, Paolo ; Ottini, Laura ; Montagna, Marco ; Agata, Simona ; Maugard, Christine ; Simard, Jacques ; Soucy, Penny ; Berger, Andreas ; Fink-Retter, Anneliese ; Singer, Christian F. ; Rappaport, Christine ; Geschwantler-Kaulich, Daphne ; Tea, Muy-Kheng ; Pfeiler, Georg ; John, Esther M. ; Miron, Alex ; Neuhausen, Susan L. ; Terry, Mary Beth ; Chung, Wendy K. ; Daly, Mary B. ; Goldgar, David E. ; Janavicius, Ramunas ; Dorfling, Cecilia M. ; Van Rensburg, Elisabeth J. ; Fostira, Florentia ; Konstantopoulou, Irene ; Garber, Judy ; Godwin, Andrew K. ; Olah, Edith ; Narod, Steven A. ; Rennert, Gad ; Paluch, Shani Shimon ; Laitman, Yael ; Friedman, Eitan ; Liljegren, Annelie ; Rantala, Johanna ; Stenmark-Askmalm, Marie ; Loman, Niklas ; Imyanitov, Evgeny N. ; Hamann, Ute ; Spurdle, Amanda B. ; Healey, Sue ; Weitzel, Jeffrey N. ; Herzog, Josef ; Margileth, David ; Gorrini, Chiara ; Esteller, Manel ; Gómez, Antonio ; Sayols, Sergi ; Vidal, Enrique ; Heyn, Holger ; Stoppa-Lyonnet, Dominique ; Léoné, Melanie ; Barjhoux, Laure ; Fassy-Colcombet, Marion ; Pauw, Antoine de ; Lasset, Christine ; Fert Ferrer, Sandra ; Castera, Laurent ; Berthet, Pascaline ; Cornelis, François ; Bignon, Yves-Jean ; Damiola, Francesca ; Mazoyer, Sylvie ; Sinilnikova, Olga M. ; Maxwell, Christopher A. ; Vijai, Joseph ; Robson, Mark ; Kauff, Noah ; Corines, Marina J. ; Villano, Danylko ; Cunningham, Julie ; Lee, Adam ; Lindor, Noralane ; Lázaro, Conxi ; Easton, Douglas F. ; Offit, Kenneth ; Chenevix-Trench, Georgia ; Couch, Fergus J. ; Antoniou, Antonis C. ; Pujana, Miguel Angel
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10\(^{-4}\) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p\(_{interaction}\) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
Ferreira, Manuel A. ; Gamazon, Eric R. ; Al-Ejeh, Fares ; Aittomäki, Kristiina ; Andrulis, Irene L. ; Anton-Culver, Hoda ; Arason, Adalgeir ; Arndt, Volker ; Aronson, Kristan J. ; Arun, Banu K. ; Asseryanis, Ella ; Azzollini, Jacopo ; Balmaña, Judith ; Barnes, Daniel R. ; Barrowdale, Daniel ; Beckmann, Matthias W. ; Behrens, Sabine ; Benitez, Javier ; Bermisheva, Marina ; Bialkowska, Katarzyna ; Blomqvist, Carl ; Bogdanova, Natalia V. ; Bojesen, Stig E. ; Bolla, Manjeet K. ; Borg, Ake ; Brauch, Hiltrud ; Brenner, Hermann ; Broeks, Annegien ; Burwinkel, Barbara ; Caldés, Trinidad ; Caligo, Maria A. ; Campa, Daniele ; Campbell, Ian ; Canzian, Federico ; Carter, Jonathan ; Carter, Brian D. ; Castelao, Jose E. ; Chang-Claude, Jenny ; Chanock, Stephen J. ; Christiansen, Hans ; Chung, Wendy K. ; Claes, Kathleen B. M. ; Clarke, Christine L. ; Couch, Fergus J. ; Cox, Angela ; Cross, Simon S. ; Czene, Kamila ; Daly, Mary B. ; de la Hoya, Miguel ; Dennis, Joe ; Devilee, Peter ; Diez, Orland ; Dörk, Thilo ; Dunning, Alison M. ; Dwek, Miriam ; Eccles, Diana M. ; Ejlertsen, Bent ; Ellberg, Carolina ; Engel, Christoph ; Eriksson, Mikael ; Fasching, Peter A. ; Fletcher, Olivia ; Flyger, Henrik ; Friedman, Eitan ; Frost, Debra ; Gabrielson, Marike ; Gago-Dominguez, Manuela ; Ganz, Patricia A. ; Gapstur, Susan M. ; Garber, Judy ; García-Closas, Montserrat ; García-Sáenz, José A. ; Gaudet, Mia M. ; Giles, Graham G. ; Glendon, Gord ; Godwin, Andrew K. ; Goldberg, Mark S. ; Goldgar, David E. ; González-Neira, Anna ; Greene, Mark H. ; Gronwald, Jacek ; Guenél, Pascal ; Haimann, Christopher A. ; Hall, Per ; Hamann, Ute ; He, Wei ; Heyworth, Jane ; Hogervorst, Frans B. L. ; Hollestelle, Antoinette ; Hoover, Robert N. ; Hopper, John L. ; Hulick, Peter J. ; Humphreys, Keith ; Imyanitov, Evgeny N. ; Isaacs, Claudine ; Jakimovska, Milena ; Jakubowska, Anna ; James, Paul A. ; Janavicius, Ramunas ; Jankowitz, Rachel C. ; John, Esther M. ; Johnson, Nichola ; Joseph, Vijai ; Karlan, Beth Y. ; Khusnutdinova, Elza ; Kiiski, Johanna I. ; Ko, Yon-Dschun ; Jones, Michael E. ; Konstantopoulou, Irene ; Kristensen, Vessela N. ; Laitman, Yael ; Lambrechts, Diether ; Lazaro, Conxi ; Leslie, Goska ; Lester, Jenny ; Lesueur, Fabienne ; Lindström, Sara ; Long, Jirong ; Loud, Jennifer T. ; Lubiński, Jan ; Makalic, Enes ; Mannermaa, Arto ; Manoochehri, Mehdi ; Margolin, Sara ; Maurer, Tabea ; Mavroudis, Dimitrios ; McGuffog, Lesley ; Meindl, Alfons ; Menon, Usha ; Michailidou, Kyriaki ; Miller, Austin ; Montagna, Marco ; Moreno, Fernando ; Moserle, Lidia ; Mulligan, Anna Marie ; Nathanson, Katherine L. ; Neuhausen, Susan L. ; Nevanlinna, Heli ; Nevelsteen, Ines ; Nielsen, Finn C. ; Nikitina-Zake, Liene ; Nussbaum, Robert L. ; Offit, Kenneth ; Olah, Edith ; Olopade, Olufunmilayo I. ; Olsson, Håkan ; Osorio, Ana ; Papp, Janos ; Park-Simon, Tjoung-Won ; Parsons, Michael T. ; Pedersen, Inge Sokilde ; Peixoto, Ana ; Peterlongo, Paolo ; Pharaoh, Paul D. P. ; Plaseska-Karanfilska, Dijana ; Poppe, Bruce ; Presneau, Nadege ; Radice, Paolo ; Rantala, Johanna ; Rennert, Gad ; Risch, Harvey A. ; Saloustros, Emmanouil ; Sanden, Kristin ; Sawyer, Elinor J. ; Schmidt, Marjanka K. ; Schmutzler, Rita K. ; Sharma, Priyanka ; Shu, Xiao-Ou ; Simard, Jaques ; Singer, Christian F. ; Soucy, Penny ; Southey, Melissa C. ; Spinelli, John J. ; Spurdle, Amanda B. ; Stone, Jennifer ; Swerdlow, Anthony J. ; Tapper, William J. ; Taylor, Jack A. ; Teixeira, Manuel R. ; Terry, Mary Beth ; Teulé, Alex ; Thomassen, Mads ; Thöne, Kathrin ; Thull, Darcy L. ; Tischkowitz, Marc ; Toland, Amanda E. ; Torres, Diana ; Truong, Thérèse ; Tung, Nadine ; Vachon, Celine M. ; van Asperen, Christi J. ; van den Ouweland, Ans M. W. ; van Rensburg, Elizabeth J. ; Vega, Ana ; Viel, Alexandra ; Wang, Qin ; Wappenschmidt, Barbara ; Weitzel, Jeffrey N. ; Wendt, Camilla ; Winqvist, Robert ; Yang, Xiaohong R. ; Yannoukakos, Drakoulis ; Ziogas, Argyrios ; Kraft, Peter ; Antoniou, Antonis C. ; Zheng, Wei ; Easton, Douglas F. ; Milne, Roger L. ; Beesley, Jonathan ; Chenevix-Trench, Georgia
Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
- 1 to 2