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

Jingmei Li, Linda S. Lindström, Jia Nee Foo, Sajjad Rafiq, Marjanka K. Schmidt, Paul D P Pharoah, Kyriaki Michailidou, Joe Dennis, Manjeet K. Bolla, Qin Wang, Laura J. Van't Veer, Sten Cornelissen, Emiel J. Rutgers, Melissa C. Southey, Carmel Apicella, Gillian S Dite, John L. Hopper, Peter A. Fasching, Lothar Haeberle, Arif B EkiciMatthias W. Beckmann, Carl Blomqvist, Taru A. Muranen, Kristiina Aittomäki, Annika Lindblom, Sara Margolin, Arto Mannermaa, Veli-Matti Kosma, Jaana M. Hartikainen, Vesa Kataja, Georgia Chenevix-Trench, Kelly-Anne Phillips, Sue-Anne McLachlan, Diether Lambrechts, Bernard Thienpont, Ann Smeets, Hans Wildiers, Jenny Chang-Claude, Dieter Flesch-Janys, Petra Seibold, Anja Rudolph, Graham G. Giles, Laura Baglietto, Gianluca Severi, Christopher A Haiman, Brian E Henderson, Fredrick Schumacher, Loic Le Marchand, Vessela Kristensen, Grethe I.Grenaker Alnæs, Anne-Lise Borresen-Dale, Silje Nord, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L Andrulis, Julia A Knight, Gord Glendon, Sandrine Tchatchou, Peter Devilee, Robert A.E.M. Tollenaar, Caroline Seynaeve, Maartje J Hooning, Mieke Kriege, Antoinette Hollestelle, Ans M W van den Ouweland, Yi Li, Ute Hamann, Diana Torres, Hans Ulrich Ulmer, Thomas Rüdiger, Chen-Yang Shen, Chia-Ni Hsiung, Pei-Ei Wu, Shou-Tung Chen, Soo-Hwang Teo, Nur Aishah Mohd Taib, Cheng Har Yip, Gwo Fuang Ho, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Kazuo Tajima, Daehee Kang, Ji Yeob Choi, Sue K. Park, Keun-Young Yoo, Tom Maishman, William J Tapper, Alison M Dunning, Mitul Shah, Robert Luben, Judith Brown, Chiea Chuen Khor, Diana M Eccles, Heli Nevanlinna, Douglas F Easton, Keith Humphreys, Jianjun Liu, Per Hall, Kamila Czene, kConFab Investigators

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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 × 10 â ̂'9). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.

Original languageEnglish
Article number4051
Number of pages9
JournalNature Communications
Publication statusPublished - 17 Jun 2014
Externally publishedYes

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