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

Oncotarget
Maral JamshidiHeli Nevanlinna

Abstract

In breast cancer, constitutive activation of NF-κB 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-κB 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-...Continue Reading

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Citations

Apr 1, 2017·BMC Systems Biology·Amin Zollanvari, Gil Alterovitz
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Methods Mentioned

BETA
genotyping
immunoprecipitation

Software Mentioned

Birdseed
Haploreg
RegulomeDB
GenCall
package Matrix eQTL
Affymetrix Genotyping Console
METABRIC
Illumina
SNAP
R

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