<b><i>IL1RN</i></b> Polymorphisms Are Associated with a Decreased Risk of Esophageal Cancer Susceptibility in a Chinese Population

Abstract

Background: Recent evidence suggested that IL1RN (interleukin-1 receptor antagonist) polymorphisms increased the susceptibility to cancers. The present study aimed to evaluate whether IL1RN was related to esophageal cancer susceptibility in a Northwest Han Chinese population. Methods: The case-control study was conducted on 384 esophageal cancer patients and 499 healthy controls. We successfully genotyped four SNPs distributed in IL1RN. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to observe the expression of IL1RN in esophageal cancer tissues and normal tissues. RegulomeDB and HaploReg v4.1 were used to calculate possible functional effects of the polymorphisms. We also used genetic models to detect any potential association between IL1RN variants and esophageal cancer risk. Results: In our study, rs3181052 was associated with a reduced risk of esophageal cancer in the codominant (odds ratio [OR] = 0.70, 95% confidence interval [CI] 0.52–0.93, p = 0.040), the dominant (OR = 0.75, 95% CI 0.57–0.99, p = 0.041), and the overdominant (OR = 0.71, 95% CI 0.54–0.93, p = 0.012) model. The rs452204 was associated with a 0.76-fold (OR = 0.76, 95% CI 0.58–0.99; p = 0.043) decreased esophageal cancer risk under the overdominant model without adjustment. We also found that rs3181052 had a negative effect on esophageal cancer under the overdominant model (OR = 0.72, 95% CI 0.53–0.97, p = 0.033) adjusted for age and gender. In stratified analyses by age >55 years, rs3181052 reduced the risk of esophageal cancer in the dominant and overdominant models. In addition, rs315919 had a remarkable influence on esophageal cancer risk in females, while the association was not significant between rs3181052 and esophageal cancer risk in males. Conclusions: Our study provided the first evidence that IL1RN rs3181052, rs452204, and rs315919 are correlated with a decreased risk of esophageal cancer in a Northwest Han Chinese population. These findings may be useful for the development of early prognostics for esophageal cancer. However, further larger studies on different ethnic populations are warranted to verify these findings.

Association between the Interleukin-1 Receptor Antagonist (IL1RN) Variable Number of Tandem Repeats (VNTR) Polymorphism and Lymphoma

“…However, a pooled analysis of three studies showed that IL1RN rs2637988 was correlated with an increased risk of NHL 22 , probably by increasing predisposition to shorter immune responses 23 . Conversely, several other polymorphisms in IL-1RN (rs3181052, rs452204 and rs315919) are associated with a decreased risk of esophageal cancer in a Northwest Han Chinese population 11 .…”

“…IL-1 is a key inflammatory cytokine that has been shown to induce tumor growth, angiogenesis, invasiveness and metastasis in various cancers 24 . IL-1RN can alter IL-1 expression levels and compete for binding spots on the IL-1 receptors, consequently modulating the effectiveness of IL-1 signaling and IL-1 related immune and inflammatory responses 11 . Despite the convincing results, our study has several limitations, which include the analysis of a relatively small sample size and the gene environmental interactions.…”

“…The IL1RN gene has an 86 bp variable number of tandem repeats (VNTR) polymorphism in the second intron. Associations between this polymorphism and some cancers have been reported in previous studies 11 , 15 - 17 , but with controversial results. In the present study, we aimed to determine whether an association exists between the presence of the IL1RN VNTR polymorphism and lymphoma risk in an Iranian population sample.…”

Identification of ITGAX and CCR1 as potential biomarkers of atherosclerosis via Gene Set Enrichment Analysis

“…IL1RN encodes a member of the interleukin-1 (IL-1) cytokine family and is related to cytokine signaling in the immune system and the IL-1 signaling pathway. 26 CXCL10 encodes a chemokine of the CXC subfamily and ligand for the receptor CXCR3. Binding of this protein to CXCR3 results in pleiotropic effects, including stimulation of monocytes, natural killer cell and T cell migration, and modulation of adhesion molecule expression.…”

RPS27 selectively regulates the expression and alternative splicing of inflammatory and immune response genes in thyroid cancer cells

“…Wang et al found that IL1RN rs315919, rs452204 and rs3181052 polymorphisms were associated with a decreased risk of esophageal cancer in a Northwest Han Chinese population. 32 Niedźwiecki et al suggested that interleukin-1 receptor antagonist (IL-1ra) might have a critical role in the development of anaplastic thyroid carcinoma and follicular thyroid carcinoma. 33 As a chemokine, platelet factor 4 (PF4, CXCL4) is involved in the pathogenesis of autoimmune thyroid diseases.…”