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

The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients.
The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients.
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.
breast cancer, survival, SNP, chemotherapy, cell cycle
1949-2553
7390-7407
Fagerholm, Rainer
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Schmidt, Marjanka K.
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Khan, Sofia
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Wildiers, Hans
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Chang-Claude, Jenny
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Seibold, Petra
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Couch, Fergus J.
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Olson, Janet E.
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Andrulis, Irene L.
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Knight, Julia A.
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Figueroa, Jonine
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Jager, Agnes
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Shah, Mitul
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Perkins, Barbara J.
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Luben, Robert
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Hamann, Ute
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Kabisch, Maria
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Czene, Kamila
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Hall, Per
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Easton, Douglas F.
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Liu, Jianjun
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Eccles, Diana
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Blomqvist, Carl
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Nevanlinna, Heli
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Fagerholm, Rainer
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Schmidt, Marjanka K.
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Khan, Sofia
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Rafiq, Sajjad
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Tapper, William
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Aittomäki, Kristiina
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Greco, Dario
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Heikkinen, Tuomas
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Muranen, Taru A.
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Fasching, Peter A.
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Janni, Wolfgang
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Weinshilboum, Richard
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Loehberg, Christian R.
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Hopper, John L.
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Southey, Melissa C.
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Lindblom, Annika
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Margolin, Sara
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Mannermaa, Arto
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Kataja, Vesa
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Lambrechts, Diether
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Wildiers, Hans
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Chang-Claude, Jenny
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Seibold, Petra
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Couch, Fergus J.
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Olson, Janet E.
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Andrulis, Irene L.
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Knight, Julia A.
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García-Closas, Montserrat
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Figueroa, Jonine
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Hooning, Maartje J.
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Jager, Agnes
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Shah, Mitul
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Perkins, Barbara J.
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Luben, Robert
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Hamann, Ute
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Kabisch, Maria
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Czene, Kamila
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Hall, Per
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Easton, Douglas F.
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Pharoah, Paul D.P.
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Liu, Jianjun
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Eccles, Diana
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Blomqvist, Carl
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Nevanlinna, Heli
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Fagerholm, Rainer, Schmidt, Marjanka K. and Khan, Sofia et al. (2015) The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients. Oncotarget, 6 (10), 7390-7407. (doi:10.18632/oncotarget.3506). (PMID:22685040)

Record type: Article

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.

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More information

e-pub ahead of print date: 10 March 2015
Published date: 10 April 2015
Keywords: breast cancer, survival, SNP, chemotherapy, cell cycle
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 380824
URI: http://eprints.soton.ac.uk/id/eprint/380824
DOI: doi:10.18632/oncotarget.3506
ISSN: 1949-2553
PURE UUID: c41da97a-f846-4a0f-8c31-c6344b8c3a0c
ORCID for William Tapper: ORCID iD orcid.org/0000-0002-5896-1889
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169

Catalogue record

Date deposited: 24 Aug 2015 09:50
Last modified: 15 Mar 2024 03:02

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Contributors

Author: Rainer Fagerholm
Author: Marjanka K. Schmidt
Author: Sofia Khan
Author: Sajjad Rafiq
Author: William Tapper ORCID iD
Author: Kristiina Aittomäki
Author: Dario Greco
Author: Tuomas Heikkinen
Author: Taru A. Muranen
Author: Peter A. Fasching
Author: Wolfgang Janni
Author: Richard Weinshilboum
Author: Christian R. Loehberg
Author: John L. Hopper
Author: Melissa C. Southey
Author: Renske Keeman
Author: Annika Lindblom
Author: Sara Margolin
Author: Arto Mannermaa
Author: Vesa Kataja
Author: Georgia Chenevix-Trench
Author: Diether Lambrechts
Author: Hans Wildiers
Author: Jenny Chang-Claude
Author: Petra Seibold
Author: Fergus J. Couch
Author: Janet E. Olson
Author: Irene L. Andrulis
Author: Julia A. Knight
Author: Montserrat García-Closas
Author: Jonine Figueroa
Author: Maartje J. Hooning
Author: Agnes Jager
Author: Mitul Shah
Author: Barbara J. Perkins
Author: Robert Luben
Author: Ute Hamann
Author: Maria Kabisch
Author: Kamila Czene
Author: Per Hall
Author: Douglas F. Easton
Author: Paul D.P. Pharoah
Author: Jianjun Liu
Author: Diana Eccles ORCID iD
Author: Carl Blomqvist
Author: Heli Nevanlinna

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