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

Fagerholm R, Schmidt MK, Khan S, Rafiq S, Tapper W, Aittomaki K, Greco D, Heikkinen T, Muranen TA, Fasching P, Janni W, Weinshilboum R, Löhberg C, Hopper JL, Southey MC, Keeman R, Lindblom A, Margolin S, Mannermaa A, Kataja V, Chenevix-Trench G, Lambrechts D, Wildiers H, Chang-Claude J, Seibold P, Couch FJ, Olson JE, Andrulis IL, Knight JA, Garcia-Closas M, Figueroa J, Hooning MJ, Jager A, Shah M, Perkins BJ, Luben R, Hamann U, Kabisch M, Czene K, Hall P, Easton DF, Pharoah PDP, Liu J, Eccles D, Blomqvist C, Nevanlinna H (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 6

Pages Range: 7390-407

Journal Issue: 10

DOI: 10.18632/oncotarget.3506

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.

Authors with CRIS profile

Involved external institutions

Helsingin yliopisto / University of Helsinki Finland (FI) Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS) Finland (FI) University of Southampton United Kingdom (GB) Genome Institute of Singapore Singapore (SG) University of Cambridge United Kingdom (GB) Karolinska Institute Sweden (SE) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Erasmus University Medical Center (MC) Netherlands (NL) National Cancer Institute (NCI) United States (USA) (US) University College London (UCL) United Kingdom (GB) Mount Sinai Hospital (MSH) Canada (CA) Mayo Clinic United States (USA) (US) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) University of Eastern Finland Finland (FI) Antoni van Leeuwenhoek Netherlands (NL) The University of Melbourne Australia (AU) Universitätsklinikum Ulm Germany (DE) Kuopio University Hospital / Pohjois-Savon sairaanhoitopiiri Finland (FI) Center for Cancer Biology (CCB) (formerly Vesalius Research Center (VRC)) Belgium (BE)

How to cite

APA:

Fagerholm, R., Schmidt, M.K., Khan, S., Rafiq, S., Tapper, W., Aittomaki, K.,... Nevanlinna, H. (2015). The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients. Oncotarget, 6(10), 7390-407. https://doi.org/10.18632/oncotarget.3506

MLA:

Fagerholm, Rainer, et al. "The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients." Oncotarget 6.10 (2015): 7390-407.

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