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Interleukin-27 rs153109 polymorphism and the risk of non-small-cell lung cancer in a Chinese population.

ABSTRACT: Non-small-cell lung cancer (NSCLC) has a multifactorial pathogenesis, and the genetic background may be one of the critical etiologic factors. Interleukin (IL)-27, a novel member of the IL-12 family, plays a vital role in antitumor immunity. The aim of the current study was to determine the association of a single nucleotide polymorphism of the IL-27 gene with the risk of NSCLC. The genotype of the IL-27 rs153109 polymorphism was analyzed in 388 patients with NSCLC and 390 healthy controls by using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. In the patients with NSCLC, the frequencies of the GG, GA, and AA genotypes and the G and A alleles were 14.0%, 56.4%, 29.6%, 42.1%, and 57.9%, respectively. There were no significant differences in the genotype and allele distributions of the IL-27 rs153109 polymorphism between the patients with NSCLC and healthy controls (P>0.05). Furthermore, no association was determined between this polymorphism and different clinical characteristics in patients with NSCLC. Taken together, these findings suggest that the IL-27 gene may not be involved in the development of NSCLC in the Chinese population.

SUBMITTER: Ge P

PROVIDER: S-EPMC4770075 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe disease-associated non-coding variants identified by genome-wide association studies (GWASs) were enriched in open chromatin regions (OCRs) and implicated in gene regulation. Genetic variants in OCRs thus may exert regulatory functions and contribute to non-small cell lung cancer (NSCLC) susceptibility.ObjectiveTo fine map potential functional variants in GWAS loci that contribute to NSCLC predisposition using chromatin accessibility and histone modification data and explore their functions by population study and biochemical experimental analyses.MethodsWe mapped the chromatin accessible regions of lung tissues using data of assay for transposase-accessible chromatin using sequencing (ATAC-seq) in The Cancer Genome Atlas (TCGA) and prioritized potential regulatory variants within lung cancer GWAS loci by aligning with histone signatures using data of chromatin immunoprecipitation assays followed by sequencing (ChIP-seq) in the Encyclopedia of DNA Elements (ENCODE). A two-stage case-control study with 1,830 cases and 2,001 controls was conducted to explore the associations between candidate variants and NSCLC risk in Chinese population. Bioinformatic annotations and biochemical experiments were performed to further reveal the potential functions of significant variants.ResultsSixteen potential functional single-nucleotide polymorphisms (SNPs) were selected as candidates from bioinformatics analyses. Three variants out of the 16 candidate SNPs survived after genotyping in stage 1 case-control study, and only the results of SNP rs13064999 were successfully validated in the analyses of stage 2 case-control study. In combined analyses, rs13064999 was significantly associated with NSCLC risk [additive model; odds ratio (OR) = 1.17; 95%CI, 1.07-1.29; p = 0.001]. Functional annotations indicated its potential enhancer bioactivity, and dual-luciferase reporter assays revealed a significant increase in luciferase activity for the reconstructed plasmid with rs13064999 A allele, when compared to the one with wild-type G allele (pA549 < 0.001, pSK-MES-1 = 0.004). Further electrophoretic mobility shift assays (EMSA) and super-shift assays confirmed a stronger affinity of HP1γ for the binding motif containing SNP rs13064999 A allele.ConclusionThese findings suggested that the functional variant rs13064999, identified by the integration of ATAC-seq and ChIP-seq data, contributes to the susceptibility of NSCLC by affecting HP1γ binding, while the exact biological mechanism awaits further exploration.

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Interleukin-27 rs153109 polymorphism and the risk of non-small-cell lung cancer in a Chinese population.

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