SNP-SNP interaction analysis of NF-?B signaling pathway on breast cancer survival

Beitrag in einer Fachzeitschrift

Details zur Publikation

Autorinnen und Autoren: Jamshidi M, Fagerholm R, Khan S, Aittomaki K, Czene K, Darabi H, Li J, Andrulis IL, Chang-Claude J, Devilee P, Fasching P, Michailidou K, Bolla MK, Dennis J, Wang Q, Guo Q, Rhenius V, Cornelissen S, Rudolph A, Knight JA, Löhberg C, Burwinkel B, Marme F, Hopper JL, Southey MC, Bojesen SE, Flyger H, Brenner H, Holleczek B, Margolin S, Mannermaa A, Kosma VM, Van Dyck L, Nevelsteen I, Couch FJ, Olson JE, Giles GG, Mclean C, Haiman CA, Henderson BE, Winqvist R, Pylkas K, Tollenaar RAEM, Garcia-Closas M, Figueroa J, Hooning MJ, Martens JWM, Cox A, Cross SS, Simard J, Dunning AM, Easton DF, Pharoah PDP, Hall P, Blomqvist C, Schmidt MK, Nevanlinna H
Zeitschrift: Oncotarget
Jahr der Veröffentlichung: 2015
Band: 6
Heftnummer: 35
Seitenbereich: 37979-94
ISSN: 1949-2553


In breast cancer, constitutive activation of NF-?B has been reported, however, the impact of genetic variation of the pathway on patient prognosis has been little studied. Furthermore, a combination of genetic variants, rather than single polymorphisms, may affect disease prognosis. Here, in an extensive dataset (n = 30,431) from the Breast Cancer Association Consortium, we investigated the association of 917 SNPs in 75 genes in the NF-?B pathway with breast cancer prognosis. We explored SNP-SNP interactions on survival using the likelihood-ratio test comparing multivariate Cox' regression models of SNP pairs without and with an interaction term. We found two interacting pairs associating with prognosis: patients simultaneously homozygous for the rare alleles of rs5996080 and rs7973914 had worse survival (HRinteraction 6.98, 95% CI=3.3-14.4, P=1.42E-07), and patients carrying at least one rare allele for rs17243893 and rs57890595 had better survival (HRinteraction 0.51, 95% CI=0.3-0.6, P = 2.19E-05). Based on in silico functional analyses and literature, we speculate that the rs5996080 and rs7973914 loci may affect the BAFFR and TNFR1/TNFR3 receptors and breast cancer survival, possibly by disturbing both the canonical and non-canonical NF-?B pathways or their dynamics, whereas, rs17243893-rs57890595 interaction on survival may be mediated through TRAF2-TRAIL-R4 interplay. These results warrant further validation and functional analyses.

FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe

Einrichtungen weiterer Autorinnen und Autoren

Antoni van Leeuwenhoek
Cancer Council Victoria
Copenhagen University Hospital
Deutsches Krebsforschungszentrum (DKFZ)
Erasmus University Medical Center
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Helsingin yliopisto / University of Helsinki
Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS)
Karolinska Institute
Krebsregister Saarland / Saarland Cancer Registry
Leiden University
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Monash University
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
Oulun Yliopisto / University of Oulo
Ruprecht-Karls-Universität Heidelberg
The University of Melbourne
Universität Ulm
Université Laval (UL)
University College London (UCL)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of Cambridge
University of Copenhagen
University of Eastern Finland
University of Sheffield
University of Southern California (USC)


Jamshidi, M., Fagerholm, R., Khan, S., Aittomaki, K., Czene, K., Darabi, H.,... Nevanlinna, H. (2015). SNP-SNP interaction analysis of NF-?B signaling pathway on breast cancer survival. Oncotarget, 6(35), 37979-94.

Jamshidi, Maral, et al. "SNP-SNP interaction analysis of NF-?B signaling pathway on breast cancer survival." Oncotarget 6.35 (2015): 37979-94.


Zuletzt aktualisiert 2019-25-04 um 15:08