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

0435639 - ÚEM 2015 RIV US eng J - Journal Article
Lu, S. - Pardini, B. - Cheng, B. - Naccarati, A. - Huhn, S. - Vymetálková, Veronika - Vodičková, Ludmila - Buchler, T. - Hemminki, K. - Vodička, Pavel - Försti, A.
Single Nucleotide Polymorphisms within Interferon Signaling Pathway Genes Are Associated with Colorectal Cancer Susceptibility and Survival.
PLoS ONE. Roč. 9, č. 10 (2014), e11161. ISSN 1932-6203. E-ISSN 1932-6203
R&D Projects: GA ČR GAP304/10/1286; GA ČR(CZ) GAP304/12/1585
Grant - others:GA MŠk(CZ) COST Action BM1206
Institutional support: RVO:68378041
Keywords : colorectal cancer * interferon * nutrition
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.234, year: 2014

Interferon (IFN) signaling plays an important role in colorectal carcinogenesis. We examined 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. The study covered 74 single nucleotidepolymorphisms (SNPs), analysed in of 1327 CRC cases and 758 healthy controls from the Czech Republic. In 483 patients associations with overall and event-free survival were investigated as well. Seven SNPs in IFNA1, IFNA13, IFNA21, IFNK, IFNAR1 and IFNGR1 were associated with CRC risk. Multiple testing correction revealed the associations with the SNPs rs2856968 (IFNAR1) and rs2234711 (IFNGR1) (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 rs6475526 as 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.
Permanent Link: http://hdl.handle.net/11104/0239535