SNP-SNP interaction analysis of NF-κB signaling pathway on breast cancer survival
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SNP-SNP interaction analysis of NF-κB signaling pathway on breast cancer survival. / Jamshidi, Maral; Fagerholm, Rainer; Khan, Sofia; Aittomäki, Kristiina; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Andrulis, Irene L; Chang-Claude, Jenny; Devilee, Peter; Fasching, Peter A; Michailidou, Kyriaki; Bolla, Manjeet K; Dennis, Joe; Wang, Qin; Guo, Qi; Rhenius, Valerie; Cornelissen, Sten; Rudolph, Anja; Knight, Julia A; Loehberg, Christian R; Burwinkel, Barbara; Marme, Frederik; Hopper, John L; Southey, Melissa C; Bojesen, Stig E; Flyger, Henrik; Brenner, Hermann; Holleczek, Bernd; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Van Dyck, Laurien; Nevelsteen, Ines; Couch, Fergus J; Olson, Janet E; Giles, Graham G; McLean, Catriona; Haiman, Christopher A; Henderson, Brian E; Winqvist, Robert; Pylkäs, Katri; Tollenaar, Rob A E M; García-Closas, Montserrat; Figueroa, Jonine; Hooning, Maartje J; Martens, John W M; Cox, Angela; Cross, Simon S; Simard, Jacques; kConFab Investigators.
In: OncoTarget, Vol. 6, No. 35, 10.11.2015, p. 37979-94.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - SNP-SNP interaction analysis of NF-κB signaling pathway on breast cancer survival
AU - Jamshidi, Maral
AU - Fagerholm, Rainer
AU - Khan, Sofia
AU - Aittomäki, Kristiina
AU - Czene, Kamila
AU - Darabi, Hatef
AU - Li, Jingmei
AU - Andrulis, Irene L
AU - Chang-Claude, Jenny
AU - Devilee, Peter
AU - Fasching, Peter A
AU - Michailidou, Kyriaki
AU - Bolla, Manjeet K
AU - Dennis, Joe
AU - Wang, Qin
AU - Guo, Qi
AU - Rhenius, Valerie
AU - Cornelissen, Sten
AU - Rudolph, Anja
AU - Knight, Julia A
AU - Loehberg, Christian R
AU - Burwinkel, Barbara
AU - Marme, Frederik
AU - Hopper, John L
AU - Southey, Melissa C
AU - Bojesen, Stig E
AU - Flyger, Henrik
AU - Brenner, Hermann
AU - Holleczek, Bernd
AU - Margolin, Sara
AU - Mannermaa, Arto
AU - Kosma, Veli-Matti
AU - Van Dyck, Laurien
AU - Nevelsteen, Ines
AU - Couch, Fergus J
AU - Olson, Janet E
AU - Giles, Graham G
AU - McLean, Catriona
AU - Haiman, Christopher A
AU - Henderson, Brian E
AU - Winqvist, Robert
AU - Pylkäs, Katri
AU - Tollenaar, Rob A E M
AU - García-Closas, Montserrat
AU - Figueroa, Jonine
AU - Hooning, Maartje J
AU - Martens, John W M
AU - Cox, Angela
AU - Cross, Simon S
AU - Simard, Jacques
AU - kConFab Investigators
PY - 2015/11/10
Y1 - 2015/11/10
N2 - 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.
AB - 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.
U2 - 10.18632/oncotarget.4991
DO - 10.18632/oncotarget.4991
M3 - Journal article
C2 - 26317411
VL - 6
SP - 37979
EP - 37994
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 35
ER -
ID: 160866687