Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

作者：Antonis C. Antoniou, Jonathan Beesley, Lesley McGuffog, Olga M. Sinilnikova, Sue Healey, Susan L. Neuhausen, Yuan Chun Ding, Timothy R. Rebbeck, Jeffrey N. Weitzel, Henry T. Lynch, Claudine Isaacs, Patricia A. Ganz, Gail E. Tomlinson, Olufunmilayo I. Olopade, Fergus J. Couch, Xianshu Wang, Noralane M. Lindor, V. Shane Pankratz, Paolo Radice, Siranoush Manoukian, Bernard Peissel, Daniela Zaffaroni, Monica Barile, Alessandra Viel, Anna Allavena, Valentina Dall’Olio, Paolo Peterlongo, Csilla I. Szabo, Michal Zikán, Kathleen Claes, Bruce Poppe, Lenka Foretová, Phuong L. Mai, Mark H. Greene, Gad Rennert, Flavio Lejbkowicz, Gord Glendon, Hilmi Özçelik, Irene L. Andrulis, Mads Thomassen, Anne‐Marie Gerdes, Lone Sunde, Dorthe Gylling Crüger, Uffe Birk Jensen, Maria A. Caligo, Eitan Friedman, Bella Kaufman, Yael Laitman, Roni Milgrom, Maya Dubrovsky, Shimrit Cohen, Åke Borg, Helena Jernström, Annika Lindblom, Johanna Rantala, Marie Stenmark-Askmalm, Beatrice Melin, Kate Nathanson, Susan M. Domchek, Anna Jakubowska, Jan Lubiński, Tomasz Huzarski, Ana Osório, Adriana Lasa, M. Durán, María‐Isabel Tejada, Javier Godino, Javier Benı́tez, Ute Hamann, Mieke Kriege, Nicoline Hoogerbrugge, Rob B. van der Luijt, Christi J. van Asperen, Peter Devilee, E.J. Meijers-Heijboer, Marinus J. Blok, Cora M. Aalfs, Frans B.L. Hogervorst, Matti A. Rookus, Margaret Cook, Clare Oliver, Debra Frost, Don Conroy, D. Gareth Evans, Fiona Lalloo, Gabriella Pichert, Rosemarie Davidson, Trevor Cole, Jackie Cook, Joan Paterson, Shirley Hodgson, Patrick J. Morrison, Mary Porteous, Lisa Walker, Michael J. Kennedy, Huw Dorkins, Susan Peock, Andrew K. Godwin, Dominique Stoppa‐Lyonnet, Antoine De Pauw, Sylvie Mazoyer, Valérie Bonadona, Christine Lasset, Hélène Dreyfus, Dominique Leroux, Agnès Hardouin, Pascaline Berthet, Laurence Faivre, Catherine Loustalot, Tetsuro Noguchi, Hagay Sobol, Étienne Rouleau, Catherine Noguès, Marc Frénay, Laurence Venat‐Bouvet, John L. Hopper, Mary B. Daly, Mary Beth Terry, Esther M. John, Saundra S. Buys, Yosuf Yassin, Alexander Miron, David E. Goldgar, Christian F. Singer, Anne Catharina Dressler, Daphne Gschwantler‐Kaulich, Georg Pfeiler, Thomas van Overeem Hansen, Lars Jønson, Bjarni A. Agnarsson, Tomas Kirchhoff, Kenneth Offit, Vincent J. Devlin, Ana Dutra-Clarke, Marion Piedmonte, Gustavo C. Rodriguez, Katie Wakeley, John F. Boggess, Jack Basil, Peter E. Schwartz, Stephanie V. Blank, Amanda E. Toland, Marco Montagna, Cinzia Casella, Evgeny Imyanitov, Laima Tihomirova, Ignacio Blanco, Conxi Lázaro, Susan J. Ramus, Lara Sucheston, Beth Y. Karlan, Jenny Gross, Rita K. Schmutzler, Barbara Wappenschmidt, Christoph Engel, Alfons Meindl, Magdalena Lochmann, Norbert Arnold, Simone Heidemann, Raymonda Varon-Mateeva, Dieter Niederacher, Christian Sutter, Helmut Deißler, Dorothea Gadzicki, Sabine Preisler‐Adams, Karin Kast, Ines Schönbuchner, Trinidad Caldés, Miguel de la Hoya, Kristiina Aittomäki, Heli Nevanlinna, Jacques Simard, Amanda B. Spurdle, Helene Holland, Xiaoqing Chen, Radka Platte, Georgia Chenevix‐Trench, Douglas F. Easton · 发表于：Cancer Research · 年份：2010 · DOI：10.1158/0008-5472.can-10-1907 · 被引用次数：184 · 研究领域：BRCA gene mutations in cancer、Genetic Associations and Epidemiology、Nutrition, Genetics, and Disease

The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10(-11) - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., bet...