2015
SNP-SNP interaction analysis of NF-κB signaling pathway on breast cancer survival
Publication
Publication
Oncotarget , Volume 6 - Issue 35 p. 37979- 37994
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-canonical NF-κB 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.
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| doi.org/10.18632/oncotarget.4991, hdl.handle.net/1765/83939 | |
| Oncotarget | |
| Organisation | Erasmus MC: University Medical Center Rotterdam |
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Jamshidi, M., Fagerholm, R., Khan, S., Aittomäki, K., Czene, K., Darabi, H., … Nevanlinna, H. (2015). SNP-SNP interaction analysis of NF-κB signaling pathway on breast cancer survival. Oncotarget, 6(35), 37979–37994. doi:10.18632/oncotarget.4991 |
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