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Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

2014; BioMed Central; Volume: 16; Issue: 6 Linguagem: Inglês

10.1186/s13058-014-0492-9

1465-542X

Karoline Kuchenbaecker, Susan L. Neuhausen, Mark E. Robson, Daniel Barrowdale, Lesley McGuffog, Anna Marie Mulligan, Irene L. Andrulis, Amanda B. Spurdle, Marjanka K. Schmidt, Rita K. Schmutzler, Christoph Engel, Barbara Wappenschmidt, Heli Nevanlinna, Mads Thomassen, Melissa C. Southey, Paolo Radice, Susan J. Ramus, Susan M. Domchek, Katherine L. Nathanson, Andrew Lee, Sue Healey, Robert L. Nussbaum, Timothy R. Rebbeck, Banu K. Arun, Paul A. James, Beth Y. Karlan, Jenny Lester, Ilana Cass, Breast Cancer Family Registry, Mary Beth Terry, Mary B Daly, David E. Goldgar, Saundra S. Buys, Ramūnas Janavičius, Laima Tihomirova, Nadine Tung, Cecilia M. Dorfling, Elizabeth J. van Rensburg, Linda Steele, Thomas van Overeem Hansen, Bent Ejlertsen, Anne–Marie Gerdes, Finn C. Nielsen, Joe Dennis, Julie Cunningham, Steven N. Hart, Susan L. Slager, Ana Osório, Javier Benítez, M. Durán, Jeffrey N. Weitzel, Isaac Tafur, Mary Hander, Paolo Peterlongo, Siranoush Manoukian, Bernard Peissel, Gaia Roversi, Giulietta Scuvera, Bernardo Bonanni, P. Mariani, Sara Volorio, Riccardo Dolcetti, Liliana Varesco, Laura Papi, Maria Grazia Tibiletti, Giuseppe Giannini, Florentia Fostira, Irene Konstantopoulou, Judy Garber, Ute Hamann, Alan Donaldson, Carole Brewer, Claire Foo, D. Gareth Evans, Debra Frost, Diana Eccles, Fiona Douglas, Angela F. Brady, Jackie Cook, Marc Tischkowitz, Julian Adlard, Julian Barwell, Kai-Ren Ong, Lisa Walker, Louise Izatt, Lucy Side, Michael J. Kennedy, Mark T. Rogers, Mary Porteous, Patrick J. Morrison, Radka Platte, Ros Eeles, Rosemarie Davidson, Shirley Hodgson, Ian O. Ellis, Andrew K. Godwin, Kerstin Rhiem, Alfons Meindl, Nina Ditsch, Norbert Arnold, Hansjoerg Plendl, Dieter Niederacher, Christian Sutter, Doris Steinemann, Nadja Bogdanova-Markov, Karin Kast, Raymonda Varon-Mateeva, Shan Wang-Gohrke, Andrea Gehrig, Birgid Markiefka, Bruno Buecher, Cédrick Lefol, Dominique Stoppa-Lyonnet, Étienne Rouleau, Fabienne Prieur, Francesca Damiola, Laure Barjhoux, Laurence Faivre, Michel Longy, Nicolas Sévenet, Olga M. Sinilnikova, Sylvie Mazoyer, Stella Koutros, Virginie Caux-Moncoutier, Claudine Isaacs, Tom Van Maerken, Kathleen Claes, Marion Piedmonte, Lesley Andrews, John L. Hays, Gustavo C. Rodriguez, Miguel de la Hoya, Miguel de la Hoya, Sofia Khan, Frans B.L. Hogervorst, Cora M. Aalfs, J. Lange, Hanne Meijers‐Heijboer, Annemarie H. van der Hout, Juul Wijnen, KEP van Roozendaal, Arjen R. Mensenkamp, A M van den Ouweland, Rob B. van der Luijt, Rob B. van der Luijt, Edith Olah, Orland Dı́ez, Conxi Lázaro, Ignacio Blanco, Àlex Teulé, Mireia Menéndez, Anna Jakubowska, Jan Lubiński, Cezary Cybulski, Jacek Gronwald, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Aðalgeir Arason, Christine Maugard, Penny Soucy, Marco Montagna, Simona Agata, Manuel R. Teixeira, Curtis Olswold, Noralane Lindor, V. Shane Pankratz, Emily Hallberg, Xianshu Wang, Csilla I. Szabo, Joseph Vijai, Chris Jacobs, Marina Corines, Anne Lincoln, Andreas Berger, Anneliese Fink-Retter, Christian F. Singer, Christine Rappaport, Daphne Gschwantler Kaulich, Georg Pfeiler, Muy-Kheng Tea, Catherine M. Phelan, Lisa Phuong, Mark H. Greene, Gad Rennert, Evgeny N. Imyanitov, Gord Glendon, Amanda Ewart Toland, Anders Bojesen, Inge Søkilde Pedersen, Uffe Birk Jensen, Maria A. Caligo, Eitan Friedman, Raanan Berger, Yael Laitman, Johanna Rantala, Brita Arver, Niklas Loman, Åke Borg, Hans Ehrencrona, Olufunmilayo I. Olopade, Jacques Simard, Douglas F. Easton, Georgia Chenevix‐Trench, Kenneth Offit, Fergus J. Couch, Antonis C. Antoniou,

Gene expression and cancer classification

Abstract Introduction More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC) = 0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC = 0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC = 0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P <10 −6 in the analyses by PR status, HER2 status, TN phenotype, morphologic subtypes, histological grade and nodal involvement. Conclusions Differences in associations of common BC susceptibility alleles between BRCA1 and BRCA2 carriers and the general population are explained to a large extent by differences in the prevalence of ER-positive and ER-negative tumors. Estimates of the risks associated with these variants based on population-based studies are likely to be applicable to mutation carriers after taking ER status into account, which has implications for risk prediction.