IL1A polymorphisms is a risk factor for colorectal cancer in Chinese Han population: a case control study
BMC CANCER
Authors: Ji, Hong; Lu, Le; Huang, Jingjing; Liu, Yang; Zhang, Binchao; Tang, Hui; Sun, Dangze; Zhang, Yafei; Shang, Hao; Li, Yiming; Lu, Hongwei
Abstract
BackgroundColorectal cancer (CRC) is one of the most common cancers worldwide, and genetic variations exert distinct roles in its pathogenesis. Single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL1A) were reported to be correlated to the susceptibility of diverse cancers. The aim of this study was to assess the association of IL1A SNPs with the risk of colorectal cancer in a Chinese Han population.MethodsTo evaluate the correlation between IL1A polymorphisms and CRC risk, Agena MassARRAY platform was used for genotype determination among 248 CRC patients and 463 controls. The relationships between IL1A variants and CRC susceptibility were examined by logistic regression analysis. Stratified analysis was conducted for the association detection in males and females. Haplotype construction and analysis were applied to evaluate the potential relationship between the genetic block and the risk of CRC. SNP functional exploration was performed with available bioinformatics datasets.ResultsAfter adjusting for age and gender, the AA genotype of rs2856838 exhibited a risk association with colorectal cancer in the recessive model (adjusted OR=1.98, 95% CI: 1.05-3.72, p=0.036). With stratified analysis, the recessive models of rs3783550 (OR=2.17, 95% CI: 1.03-4.60, p=0.043), rs2856838 (OR=2.58, 95% CI: 1.13-5.87, p=0.024), rs1609682 (OR=2.20, 95% CI: 1.04-4.65, p=0.040), and rs3783521 (OR=2.13, 95% CI: 1.01-4.49, p=0.048) revealed significant relationships between these variants and an increased CRC risk only in females. Bioinformatics analysis also revealed the putative functions of the selected SNPs.ConclusionsThis study demonstrated that rs2856838 could influence the susceptibility to CRC in Chinese Han population from northwest China. IL1A variants rs3783550, rs2856838, rs1609682, and rs3783521 were associated with CRC risk only in females.
Synergistic Up-regulation of Cytokine Genes by CpG Oligonucleotides Plus Poly (I:C)
PROCEEDINGS OF THE 7TH JOINT MEETING OF THE INTERNATIONAL MEETING OF THE INTERNATIONAL CYTOKINE SOCIETY AND THE INTERNATIONAL SOCIETY FOR INTERFERON AND CYTOKINE RESEARCH
Authors: Petrenko, L.; Klaschik, S.; Shirota, H.; Klinman, D. M.
Abstract
RAW264.7 mouse macrophages were incubated with immunostimulatory CpG ODN and/or poly (I:C), and changes in global mRNA expression levels monitored at 4 and 12 hr using a 36 K mouse microarray. Genes encoding the cytokines IL6, IL1A, IFNA6, IFNB1, and CSF3 were synergistically up-regulated at 4 hours while those encoding IL33, IL6, IL12A, IL12B, IL19, IL10, and IL1F6 were synergistically activated at 12 hours. The interleukins IL33, IL19, IL12A, the chemokine S100A8 and the neurotransmitter NPY genes were not activated individually by either CpG ODN or poly(I:C) but were strongly up-regulated following combined stimulation. These data represent the first evidence of synergistic transcriptional activation of the interleukin genes IL33 and IL19, and help to explain the mechanism by which CpG ODN and poly(I:C) combine to enhance immune responses in vitro and in vivo.