Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.4991
Title: SNP-SNP interaction analysis of NF-?B signaling pathway on breast cancer survival
Authors: Jamshidi, M
Fagerholm, R
Khan, S
Keywords: B cell activating factor receptor
immunoglobulin enhancer binding protein
tumor necrosis factor receptor
tumor necrosis factor receptor 1
tumor necrosis factor receptor 3
tumor necrosis factor receptor associated factor 2
tumor necrosis factor related apoptosis inducing ligand
unclassified drug
immunoglobulin enhancer binding protein
tumor marker
allele
Article
breast cancer
cancer survival
gene expression
genetic variability
genotype
homozygosity
human
major clinical study
prognosis
proportional hazards model
quantitative trait locus
signal transduction
single nucleotide polymorphism
tumor gene
breast tumor
cancer grading
cancer staging
female
genetics
mortality
pathology
physiology
signal transduction
single nucleotide polymorphism
survival rate
tumor invasion
Biomarkers, Tumor
Breast Neoplasms
Female
Humans
Neoplasm Grading
Neoplasm Invasiveness
Neoplasm Staging
NF-kappa B
Polymorphism, Single Nucleotide
Prognosis
Signal Transduction
Survival Rate
Issue Date: 2015
Publisher: Impact Journals LLC
Citation: Jamshidi, M, Fagerholm, R, Khan, S (2015). SNP-SNP interaction analysis of NF-?B signaling pathway on breast cancer survival. Oncotarget 6 (35) : 37979-37994. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.4991
Rights: Attribution 4.0 International
Abstract: 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.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/180485
ISSN: 1949-2553
DOI: 10.18632/oncotarget.4991
Rights: Attribution 4.0 International
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