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Single Nucleotide Polymorphisms within Interferon Signaling Pathway Genes Are Associated with Colorectal Cancer Susceptibility and Survival.

Lu, Shun ; Pardini, Barbara ; Cheng, Bowang ; Naccarati, Alessio ; Huhn, Stefanie ; Vymetalkova, Veronika ; Vodickova, Ludmila ; Buchler, Thomas ; Hemminki, Kari LU and Vodicka, Pavel , et al. (2014) In PLoS ONE 9(10).
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
9
issue
10
article number
e111061
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:25350395
  • wos:000343943100052
  • scopus:84908567588
ISSN
1932-6203
DOI
10.1371/journal.pone.0111061
language
English
LU publication?
yes
id
a4f07325-f97b-406f-9d45-5f6d9dc5bf4c (old id 4733118)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25350395?dopt=Abstract
date added to LUP
2016-04-01 14:44:32
date last changed
2022-04-14 19:28:59
@article{a4f07325-f97b-406f-9d45-5f6d9dc5bf4c,
  abstract     = {{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&lt;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.}},
  author       = {{Lu, Shun and Pardini, Barbara and Cheng, Bowang and Naccarati, Alessio and Huhn, Stefanie and Vymetalkova, Veronika and Vodickova, Ludmila and Buchler, Thomas and Hemminki, Kari and Vodicka, Pavel and Försti, Asta}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{10}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Single Nucleotide Polymorphisms within Interferon Signaling Pathway Genes Are Associated with Colorectal Cancer Susceptibility and Survival.}},
  url          = {{https://lup.lub.lu.se/search/files/4136248/7525906}},
  doi          = {{10.1371/journal.pone.0111061}},
  volume       = {{9}},
  year         = {{2014}},
}