TY - JOUR
T1 - The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients
AU - KConFab investigators
AU - Fagerholm, Rainer
AU - Schmidt, Marjanka K.
AU - Khan, Sofia
AU - Rafiq, Sajjad
AU - Tapper, William
AU - Aittomäki, Kristiina
AU - Greco, Dario
AU - Heikkinen, Tuomas
AU - Muranen, Taru A.
AU - Fasching, Peter A.
AU - Janni, Wolfgang
AU - Weinshilboum, Richard
AU - Loehberg, Christian R.
AU - Hopper, John L.
AU - Southey, Melissa C.
AU - Keeman, Renske
AU - Lindblom, Annika
AU - Margolin, Sara
AU - Mannermaa, Arto
AU - Kataja, Vesa
AU - Chenevix-Trench, Georgia
AU - Lambrechts, Diether
AU - Wildiers, Hans
AU - Chang-Claude, Jenny
AU - Seibold, Petra
AU - Couch, Fergus J.
AU - Olson, Janet E.
AU - Andrulis, Irene L.
AU - Knight, Julia A.
AU - García-Closas, Montserrat
AU - Figueroa, Jonine
AU - Hooning, Maartje J.
AU - Jager, Agnes
AU - Shah, Mitul
AU - Perkins, Barbara J.
AU - Luben, Robert
AU - Hamann, Ute
AU - Kabisch, Maria
AU - Czene, Kamila
AU - Hall, Per
AU - Easton, Douglas F.
AU - Pharoah, Paul D.P.
AU - Liu, Jianjun
AU - Eccles, Diana
AU - Blomqvist, Carl
AU - Nevanlinna, Heli
PY - 2015
Y1 - 2015
N2 - We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.
AB - We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.
KW - Breast cancer
KW - Cell cycle
KW - Chemotherapy
KW - SNP
KW - Survival
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UR - http://www.scopus.com/inward/citedby.url?scp=84928395170&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.3506
DO - 10.18632/oncotarget.3506
M3 - Article
C2 - 25823661
AN - SCOPUS:84928395170
SN - 1949-2553
VL - 6
SP - 7390
EP - 7407
JO - Oncotarget
JF - Oncotarget
IS - 10
ER -