2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy

J Li, LS Lindstrom, JN Foo, S Rafiq, Marjanka K Schmidt, PDP Pharoah, K Michailidou, J Dennis, MK Bolla, Q (Qing) Wang, LJ (Laura) van 't Veer, S Cornelissen, E Rutgers, MC Southey, C Apicella, GS Dite, JL Hopper, PA Fasching, L Haeberle, AB EkiciMW Beckmann, C Blomqvist, TA Muranen, K Aittomaeki, A Lindblom, S Margolin, A Mannermaa, VM Kosma, JM Hartikainen, V Kataja, G Chenevix-Trench, KA Phillips, SA McLachlan, D Lambrechts, B Thienpont, A Smeets, H Wildiers, J Chang-Claude, D Flesch-Janys, P Seibold, A Rudolph, GG Giles, L Baglietto, G Severi, CA Haiman, BE Henderson, F Schumacher, L Le Marchand, V Kristensen, GIG Alnaes, AL Borresen-Dale, S Nord, R Winqvist, K Pylkas, A Jukkola-Vuorinen, M Grip, IL Andrulis, JA Knight, G Glendon, S Tchatchou, P Devilee, R Tollenaar, Caroline Seynaeve, Maartje Hooning, Mieke Kriege, Antoinette Hollestelle, Ans van den Ouweland, Y Li, U Hamann, D Torres, HU Ulmer, T Rudiger, CY Shen, CN Hsiung, PE Wu, ST Chen, SH Teo, NAM Taib, CH Yip, GF Ho, K Matsuo, H Ito, H Iwata, K Tajima, D Kang, JY Choi, SK Park, KY Yoo, T Maishman, WJ Tapper, A Dunning, M Shah, R Luben, J Brown, CC Khor, DM Eccles, H Nevanlinna, D Easton, K Humphreys, J Liu, P Hall, K Czene

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Abstract

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.
Original languageUndefined/Unknown
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 2014

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