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Statements

Subject Item
n2:RIV%2F00216208%3A11140%2F14%3A10283152%21RIV15-MSM-11140___
rdf:type
skos:Concept n16:Vysledek
rdfs:seeAlso
http://dx.doi.org/10.1371/journal.pone.0111061
dcterms:description
Interferon (IFN) signaling has been suggested to play an important role in colorectal carcinogenesis. Our study aimed to examine potentially functional genetic variants in interferon regulatory factor 3 (IRF3), IRF5, IRF7, type I and type II IFN and their receptor genes with respect to colorectal cancer (CRC) risk and clinical outcome. Altogether 74 single nucleotide polymorphisms (SNPs) were covered by the 34 SNPs genotyped in a hospital-based case-control study of 1327 CRC cases and 758 healthy controls from the Czech Republic. We also analyzed these SNPs in relation to overall survival and event-free survival in a subgroup of 483 patients. Seven SNPs in IFNA1, IFNA13, IFNA21, IFNK, IFNAR1 and IFNGR1 were associated with CRC risk. After multiple testing correction, the associations with the SNPs rs2856968 (IFNAR1) and rs2234711 (IFNGR1) remained formally significant (P = 0.0015 and P<0.0001, respectively). Multivariable survival analyses showed that the SNP rs6475526 (IFNA7/IFNA14) was associated with overall survival of the patients (P = 0.041 and event-free survival among patients without distant metastasis at the time of diagnosis, P = 0.034). The hazard ratios (HRs) for rs6475526 remained statistically significant even after adjustment for age, gender, grade and stage (P = 0.029 and P = 0.036, respectively), suggesting that rs6475526 is an independent prognostic marker for CRC. Our data suggest that genetic variation in the IFN signaling pathway genes may play a role in the etiology and survival of CRC and further studies are warranted. Interferon (IFN) signaling has been suggested to play an important role in colorectal carcinogenesis. Our study aimed to examine potentially functional genetic variants in interferon regulatory factor 3 (IRF3), IRF5, IRF7, type I and type II IFN and their receptor genes with respect to colorectal cancer (CRC) risk and clinical outcome. Altogether 74 single nucleotide polymorphisms (SNPs) were covered by the 34 SNPs genotyped in a hospital-based case-control study of 1327 CRC cases and 758 healthy controls from the Czech Republic. We also analyzed these SNPs in relation to overall survival and event-free survival in a subgroup of 483 patients. Seven SNPs in IFNA1, IFNA13, IFNA21, IFNK, IFNAR1 and IFNGR1 were associated with CRC risk. After multiple testing correction, the associations with the SNPs rs2856968 (IFNAR1) and rs2234711 (IFNGR1) remained formally significant (P = 0.0015 and P<0.0001, respectively). Multivariable survival analyses showed that the SNP rs6475526 (IFNA7/IFNA14) was associated with overall survival of the patients (P = 0.041 and event-free survival among patients without distant metastasis at the time of diagnosis, P = 0.034). The hazard ratios (HRs) for rs6475526 remained statistically significant even after adjustment for age, gender, grade and stage (P = 0.029 and P = 0.036, respectively), suggesting that rs6475526 is an independent prognostic marker for CRC. Our data suggest that genetic variation in the IFN signaling pathway genes may play a role in the etiology and survival of CRC and further studies are warranted.
dcterms:title
Single Nucleotide Polymorphisms within Interferon Signaling Pathway Genes Are Associated with Colorectal Cancer Susceptibility and Survival Single Nucleotide Polymorphisms within Interferon Signaling Pathway Genes Are Associated with Colorectal Cancer Susceptibility and Survival
skos:prefLabel
Single Nucleotide Polymorphisms within Interferon Signaling Pathway Genes Are Associated with Colorectal Cancer Susceptibility and Survival Single Nucleotide Polymorphisms within Interferon Signaling Pathway Genes Are Associated with Colorectal Cancer Susceptibility and Survival
skos:notation
RIV/00216208:11140/14:10283152!RIV15-MSM-11140___
n4:aktivita
n10:I n10:P
n4:aktivity
I, P(ED2.1.00/03.0076), P(GAP304/10/1286), P(GAP304/12/1585)
n4:cisloPeriodika
10
n4:dodaniDat
n14:2015
n4:domaciTvurceVysledku
n12:5013690
n4:druhVysledku
n9:J
n4:duvernostUdaju
n15:S
n4:entitaPredkladatele
n13:predkladatel
n4:idSjednocenehoVysledku
45078
n4:idVysledku
RIV/00216208:11140/14:10283152
n4:jazykVysledku
n18:eng
n4:klicovaSlova
expression; identification; predisposition; colon; risk; cell-lines; alpha promotes; promoter polymorphisms; ifn-gamma receptor; genome-wide metaanalysis
n4:klicoveSlovo
n7:ifn-gamma%20receptor n7:predisposition n7:cell-lines n7:expression n7:identification n7:alpha%20promotes n7:risk n7:colon n7:promoter%20polymorphisms n7:genome-wide%20metaanalysis
n4:kodStatuVydavatele
US - Spojené státy americké
n4:kontrolniKodProRIV
[A33B6038BBC4]
n4:nazevZdroje
PLoS ONE
n4:obor
n8:EB
n4:pocetDomacichTvurcuVysledku
1
n4:pocetTvurcuVysledku
11
n4:projekt
n5:ED2.1.00%2F03.0076 n5:GAP304%2F10%2F1286 n5:GAP304%2F12%2F1585
n4:rokUplatneniVysledku
n14:2014
n4:svazekPeriodika
9
n4:tvurceVysledku
Naccarati, Alessio Büchler, Tomáš Forsti, Asta Cheng, Bowang Vodička, Pavel Lu, Shun Vymetálková, Veronika Huhn, Stefanie Pardini, Barbara Hemminki, Kari Vodičková, Ludmila
n4:wos
000343943100052
s:issn
1932-6203
s:numberOfPages
11
n19:doi
10.1371/journal.pone.0111061
n17:organizacniJednotka
11140