The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients

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http://hdl.handle.net/10138/225320

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Fagerholm , R , Schmidt , M K , Khan , S , Rafiq , S , Tapper , W , Aittomaki , K , Greco , D , Heikkinen , T , Muranen , T A , Fasching , P A , Janni , W , Weinshilboum , R , Loehberg , C R , Hopper , J L , Southey , M C , Keeman , R , Lindblom , A , Margolin , S , Mannermaa , A , Kataja , V , Chenevix-Trench , G , Lambrechts , D , Wildiers , H , Chang-Claude , J , Seibold , P , Couch , F J , Olson , J E , Andrulis , I L , Knight , J A , Garcia-Closas , M , Figueroa , J , Hooning , M J , Jager , A , Shah , M , Perkins , B J , Luben , R , Hamann , U , Kabisch , M , Czene , K , Hall , P , Easton , D F , Pharoah , P D P , Liu , J , Eccles , D , Blomqvist , C , Nevanlinna , H & kConFab Investigators 2015 , ' The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients ' Oncotarget , vol. 6 , no. 10 , pp. 7390-7407 . DOI: 10.18632/oncotarget.3506

Title: The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients
Author: Fagerholm, Rainer; Schmidt, Marjanka K.; Khan, Sofia; Rafiq, Sajjad; Tapper, William; Aittomaki, Kristiina; Greco, Dario; Heikkinen, Tuomas; Muranen, Taru A.; Fasching, Peter A.; Janni, Wolfgang; Weinshilboum, Richard; Loehberg, Christian R.; Hopper, John L.; Southey, Melissa C.; Keeman, Renske; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Chenevix-Trench, Georgia; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Seibold, Petra; Couch, Fergus J.; Olson, Janet E.; Andrulis, Irene L.; Knight, Julia A.; Garcia-Closas, Montserrat; Figueroa, Jonine; Hooning, Maartje J.; Jager, Agnes; Shah, Mitul; Perkins, Barbara J.; Luben, Robert; Hamann, Ute; Kabisch, Maria; Czene, Kamila; Hall, Per; Easton, Douglas F.; Pharoah, Paul D. P.; Liu, Jianjun; Eccles, Diana; Blomqvist, Carl; Nevanlinna, Heli; kConFab Investigators
Contributor: University of Helsinki, Dep. of Medical Genetics (Haartman Institute) (-2009)
University of Helsinki, Department of Obstetrics and Gynegology
University of Helsinki, Department of Medical and Clinical Genetics
University of Helsinki, Institute of Biotechnology
University of Helsinki, Lauri Antti Aaltonen / Principal Investigator
University of Helsinki, Department of Obstetrics and Gynegology
University of Helsinki, Department of Oncology
University of Helsinki, Department of Obstetrics and Gynegology
Date: 2015-04-10
Language: eng
Number of pages: 18
Belongs to series: Oncotarget
ISSN: 1949-2553
URI: http://hdl.handle.net/10138/225320
Abstract: 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.
Subject: breast cancer
survival
SNP
chemotherapy
cell cycle
ESTROGEN-RECEPTOR-ALPHA
LARGE GENE LISTS
BRCA2 MUTATIONS
LUNG-CANCER
CELL-LINES
EXPRESSION
PROGNOSIS
OUTCOMES
REVEALS
SUSCEPTIBILITY
3122 Cancers
3123 Gynaecology and paediatrics
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