title: Interleukin 17A polymorphism elevates gene expression and is associated with increased risk of nonsmall cell lung cancer.
abstract: Interleukin 17 (IL-17), also known as IL-17A, is a proinflammatory cytokine and plays critical roles in tumor immunity. Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancers. The aim of this study was to investigate the correlation between IL-17A genetic polymorphisms and susceptibility to NSCLC. Two single nucleotide polymorphisms (SNPs) in IL-17A gene, rs3819024A/G and rs8193037G/A, were detected in 322 NSCLC patients and 366 healthy donors. Data revealed that prevalence of IL-17A rs8193037GA and AA genotypes were significantly higher in the patients than in controls (odds ratio [OR]: 2.20, 95% confidence interval [CI]: 1.53-3.16, p<0.001; and OR: 3.19, 95% CI: 1.42-7.15, p=0.003). Stratification analyses showed that rs8193037A allele had significantly higher percentage in adenocarcinoma than in squamous cell carcinoma (OR: 1.72, 95% CI: 1.12-2.64, p=0.013). When examining the possible function of the SNPs, we found that in vitro stimulated peripheral blood mononuclear cells from subjects possessing rs8193037A allele produced significantly more IL-17 than those with the GG genotype, and this phenomenon could be observed in both controls and the NSCLC patients. These data indicate IL-17A polymorphism is associated with increased risk of NSCLC probably by elevating gene expression.
authors.affiliation: 1 School of Medicine and Life Sciences, University of Jinan , Shandong Academy of Medical Sciences, Jinan, China .
authors.forename: Sensen
authors.initials: S
authors.lastname: Cheng
authors.forename: Zhulin
authors.initials: Z
authors.lastname: Shao
authors.forename: Xiuchun
authors.initials: X
authors.lastname: Liu
authors.forename: Liangjun
authors.initials: L
authors.lastname: Guo
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Qinyun
authors.initials: Q
authors.lastname: Na
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Chen
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ma
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zheng
authors.forename: Bao
authors.initials: B
authors.lastname: Song
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015854:Up-Regulation
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17