| Autor: |
Arif B. Ekici, MW Reed, S. Keith Anderson, Celine M. Vachon, Robert Pilarski, Graham G. Giles, Xianshu Wang, Susan L. Slager, Priyanka Sharma, Curtis Olswold, Dimitrios Pectasides, Douglas F. Easton, Drakoulis Yannoukakos, Sandra Deming-Halverson, Sajjad Rafiq, Christine B. Ambrosone, Matthias Ruebner, Jo Ellen Weaver, Melissa C. Southey, Brigitte Rack, Paul J. Goodfellow, Thaer Khoury, Vernon S. Pankratz, Wei Zheng, S Gerty, Martha J. Shrubsole, Ruediger Schulz-Wendtland, Alexander Hein, Jennifer Ivanovich, George Fountzilas, Stefan Nickels, Hugues Sicotte, Diana Eccles, Simon S. Cross, Seth W. Slettedahl, Christoph Scholz, Matthias W. Beckmann, Dieter Flesch-Janys, Jianjun Liu, Meletios A. Dimopoulos, Päivi Heikkilä, Hoda Anton-Culver, Wolfgang Janni, Julia Neugebauer, Veli-Matti Kosma, Hans Ulrich Ulmer, Charles L. Shapiro, Janet E. Olson, James N. Ingle, Andrew K. Godwin, Nicholas G. Martin, Kristiina Aittomäki, Arndt Hartmann, Irene Konstantopoulou, Thomas Rüdiger, Angela Cox, Mary B. Daly, Hiltrud Brauch, Carl Blomqvist, Nirmala Pathmanathan, Dimosthenis Skarlos, William J. Tapper, Ulrich Andergassen, Heli Nevanlinna, Irene Konstanta, Athanassios Vratimos, Heidrun Wölfing, Sotiris Lakis, Asta Försti, Florentia Fostira, Jenny Chang-Claude, Christine L. Clarke, Dario Greco, Gianluca Severi, Xiao-Ou Shu, Lothar Haeberle, Jennifer R. Klemp, Shicha Kumar, Diana Torres, Argyrios Ziogas, Anja Rudolph, Hans Fischer, Arto Mannermaa, Victoria Cafourek, Vessela N. Kristensen, Eric A. Ross, Paraskevi Apostolou, Leslie Bernstein, Vassiliki Kotoula, Laura Baglietto, Elisabete Weiderpass, Kristen S. Purrington, Qiuyin Cai, Lorraine Durcan, Jane Carpenter, Jeanette E. Eckel-Passow, Grant W. Montgomery, Peter A. Fasching, Stefan P. Renner, Astrid Irwanto, Fergus J. Couch, Penelope Miron, Ute Hamann, Naresh Prodduturi, Amanda E. Toland, Michael P. Lux, Daniel W. Visscher, Per Hall |
| Popis: |
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. |
