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

Li J, Lindstrom LS, Foo JN, Rafiq S, Schmidt MK, Pharoah PD, Michailidou K, Dennis J, Bolla MK, Wang Q, Van 't Veer LJ, Cornelissen S, Rutgers E, Southey MC, Apicella C, Dite GS, Hopper JL, Fasching PA, Haeberle L, Ekici AB, Beckmann MW, Blomqvist C, Muranen TA, Aittomaki K, Lindblom A, Margolin S, Mannermaa A, Kosma VM, Hartikainen JM, Kataja V, Chenevix-Trench G, Investigators k, Phillips KA, McLachlan SA, Lambrechts D, Thienpont B, Smeets A, Wildiers H, Chang-Claude J, Flesch-Janys D, Seibold P, Rudolph A, Giles GG, Baglietto L, Severi G, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Kristensen V, Alnaes GI, Borresen-Dale AL, Nord S, Winqvist R, Pylkas K, Jukkola-Vuorinen A, Grip M, Andrulis IL, Knight JA, Glendon G, Tchatchou S, Devilee P, Tollenaar R, Seynaeve C, Hooning M, Kriege M, Hollestelle A, van den Ouweland A, Li Y, Hamann U, Torres D, Ulmer HU, Rudiger T, Shen CY, Hsiung CN, Wu PE, Chen ST, Teo SH, Taib NA, Har Yip C, Fuang Ho G, Matsuo K, Ito H, Iwata H, Tajima K, Kang D, Choi JY, Park SK, Yoo KY, Maishman T, Tapper WJ, Dunning A, Shah M, Luben R, Brown J, Chuen Khor C, Eccles DM, Nevanlinna H, Easton D, Humphreys K, Liu J, Hall P, Czene K (2014) 2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy. Nature communications 5:4051

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.