Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 x 10(-9)). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.
| Authors | Li, Jingmei; Lindstroem, Linda S.; Foo, Jia-Nee; Rafiq, Sajjad; Schmidt, Marjanka K.; Pharoah, Paul D. P.; Michailidou, Kyriaki; Dennis, Joe; Bolla, Manjeet K.; Wang, Qin; Van't Veer, Laura J.; Cornelissen, Sten; Rutgers, Emiel J.; Southey, Melissa; Apicella, C; Dite, Gillian S.; Hopper, John L.; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Blomqvist, Carl; Muranen, Taru A.; Aittomaeki, Kristiina; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana; Kataja, Vesa; Chenevix-Trench, G; Phillips, Kelly-Anne; McLachlan, Sue-Anne; Lambrechts, Diether; Thienpont, Bernard; Smeets, Ann; Wildiers, Hans; Chang-Claude, Jenny; Flesch-Janys, Dieter; Seibold, Petra; Rudolph, Anja; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Kristensen, Vessela N.; Alnaes, Grethe I. Grenaker; Borresen-Dale, Anne-Lise; Nord, Silje; Winqvist, Robert; Pylkas, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Rob A. E. M.; Seynaeve, Caroline; Hooning, Maartje J.; Kriege, Mieke; Hollestelle, Antoinette; van den Ouweland, Ans; Hamann, Ute; Torres, Diana; Ulmer, Hans Ulrich; Rudiger, Thomas; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Chen, Shou-Tung; Teo, Soo Hwang; Taib, Nur Aishah Mohd; Yip, Cheng Har; Ho, Gwo Fuang; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Yoo, Keun-Young; Maishman, Tom; Tapper, William J.; Dunning, Alison M.; Shah, Mitul; Luben, Robert; Brown, Judith; Khor, Chiea Chuen; Eccles, Diana; Nevanlinna, Heli; Easton, Douglas; Humphreys, Keith; Liu, Jianjun; Hall, Per; Czene, Kamila |
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| Journal | Nature Communications |
| Pages | 4051 |
| Volume | 5 |
| Date | 1/06/2014 |
| Grant ID | |
| Funding Body | NHMRC |
| URL | http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1038/ncomms5051 |
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