Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer
Year: 2013
Type: article
Study design: Observational Study
Abstract: Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 × 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.
Source: Carcinogenesis
Authors: Kristen S. Purrington, Susan Slager, Diana Eccles, Drakoulis Yannoukakos, Peter A. Fasching, Penelope Miron, Jane Carpenter, Jenny Chang-Claude, Nicholas G. Martin, Grant W. Montgomery, Vessela Kristensen, Hoda Anton-Culver, Paul Goodfellow, William J. Tapper, Sajjad Rafiq, Susan M. Gerty, Lorraine Durcan, Irene Konstantopoulou, Florentia Fostira, Athanassios Vratimos, Paraskevi Apostolou, Irene Konstanta, Vassiliki Kotoula, Sotiris Lakis, Meletios A. Dimopoulos, Dimosthenis Skarlos, Dimitrios Pectasides, George Fountzilas, Matthias W. Beckmann, Alexander Hein, Matthias Ruebner, Arif B. Ekici, Arndt Hartmann, Ruediger Schulz-Wendtland, Stefan P. Renner, Wolfgang Janni, Brigitte Rack, Christoph Scholz, Julia Neugebauer, Ulrich Andergassen, Michael P. Lux, Lothar Haeberle, Christine Clarke, Nirmala Pathmanathan, Anja Rudolph, Dieter Flesch-Janys, Stefan Nickels, Janet E. Olson, James N. Ingle, Curtis Olswold, Seth Slettedahl, Jeanette E. Eckel-Passow, S.Keith Anderson, Daniel W. Visscher, Victoria L. Cafourek, Hugues Sicotte, Naresh Prodduturi, Elisabete Weiderpass, Leslie Bernstein, Argyrios Ziogas, Jennifer Ivanovich, Graham G. Giles, Laura Baglietto, Melissa Southey, Veli-Matti Kosma, Hans-Peter Fischer, Malcom W.R. Reed, Simon S. Cross, Sandra Deming-Halverson, Martha Shrubsole, Qiuyin Cai, Xiao-Ou Shu, Mary Daly, JoEllen Weaver, Eric Ross, Jennifer Klemp, Priyanka Sharma, Diana Torres, Thomas Rüdiger, Heidrun Wölfing, Hans-Ulrich Ulmer, Asta Försti, Thaer Khoury, Shicha Kumar, Robert Pilarski, Charles L. Shapiro, Dario Greco, Päivi Heikkilä, Kristiina Aittomäki, Carl Blomqvist, Astrid Irwanto, Jianjun Liu, Vernon Shane Pankratz, Xianshu Wang, Gianluca Severi, Arto Mannermaa, Douglas Easton, Per Hall, Hiltrud Brauch, Angela Cox, Wei Zheng, Andrew K. Godwin, Ute Hamann, Christine Ambrosone, Amanda Ewart Toland, Heli Nevanlinna, Celine M. Vachon, Fergus J. Couch
Institutions: Mayo Clinic, University of Southampton, National Centre of Scientific Research "Demokritos", University of California, Los Angeles, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Dana-Farber Cancer Institute, The University of Sydney, German Cancer Research Center, QIMR Berghofer Medical Research Institute, Oslo University Hospital, University of Oslo, University of California, Irvine, Barnes-Jewish Hospital, Washington University in St. Louis, Alvin J. Siteman Cancer Center, Aristotle University of Thessaloniki, National and Kapodistrian University of Athens, Alexandra Hospital, Metropolitan Hospital, Hippocration General Hospital, Papageorgiou General Hospital, University Hospital Ulm, Ludwig-Maximilians-Universität München, Westmead Hospital, Universität Hamburg, University Medical Center Hamburg-Eppendorf, Cancer Registry of Norway, Folkhälsans Forskningscentrum, UiT The Arctic University of Norway, City Of Hope National Medical Center, City of Hope, Beckman Research Institute, Cancer Council Victoria, The University of Melbourne, University of Eastern Finland, Kuopio University Hospital, University of Bonn, Yorkshire Cancer Research, Cancer Research UK, University of Sheffield, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Fox Chase Cancer Center, University of Pennsylvania, University of Kansas Medical Center, Pontificia Universidad Javeriana, Städtisches Klinikum Karlsruhe, Klinikum Mittelbaden, Lund University, Roswell Park Comprehensive Cancer Center, The Ohio State University, Helsinki University Hospital, Genome Institute of Singapore, University of Cambridge, Karolinska Institutet, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: Mayo Clinic, Breast Cancer Research Foundation, Kansas Bioscience Authority, Deutsches Krebsforschungszentrum, David F. and Margaret T. Grohne Family Foundation, Cancer Research UK, European Commission, Robert Bosch Stiftung, Bundesministerium für Bildung und Forschung, Deutsche Gesetzliche Unfallversicherung, National Institutes of Health, Cancer Center, University of Kansas, National Cancer Institute, European Social Fund
Awards: G1040152257, G1119587714, A genome-wide association study for breast cancer in BRCA1 mutation carriers, G1498657983, G1651766810, G1698401662, G1768507827, Breast and Other Cancers in the California Teachers Cohort, G2031173712, Verbundprojekt: Verbund 'Brustkrebs': Mammakarzinomrisiko und prädiktive Faktoren, G2318886995, G2322645988, G2384450127, Verbundprojekt: Verbund 'Brustkrebs': Assoziation mit genetischen Polymorphismen und Expression von Enzymen des Fremdstoffmetabolismus, Verbundprojekt: Verbund 'Brustkrebs': Mammakarzinomrisiko und prädiktive Faktoren - Assoziation mit genetischen Polymorphismen und Expression von Enzymen des Fremdstoffmetabolismus, G2620224376, Exploiting Biological Networks to Improve Clinical Treatment of Ovarian Cancer, G2767427565, G2810223295, G2981953317, G3120329307, G3139222247, G3146423343, G3374092061, G3791275145, Verbundprojekt: Verbund 'Brustkrebs': Mammakarzinomrisiko und prädiktive Faktoren, G3983849296, G4029743399, G4115289818, Mayo Cancer Genetic Epidemiology Training Program, G424082930, G4324572255, G4333708648, G4390033113, Fox Chase Clinical Epidemiology and Validation Center, G4601496266, G4645104295, G5468790521, G5655665560, G5671701345, G5677485672, G5991032111, G6195211026, G6471584761, G6535168135, G6557157180, G7502883741, G7683724993, G7820459769, G7946625978, G8092145710, G8230221726, G8283179918, G835355920, G8658736651, G9000108363, Mayo Clinic Comprehensive Cancer Center Support Grant, The University of Kansas Cancer Center, Mayo Clinic Breast Cancer SPORE
OpenAlex ID: W2117505014