Interleukin 17A genetic variations and susceptibility to non-small cell lung cancer.

ABSTRACT

Lung cancer is the leading cause of cancer-related death, in which non-small cell lung cancer (NSCLC) is the most common type. Evidence have shown that interleukin 17 (IL-17) greatly involves in human immune responses. In this study, we investigated the effect of IL-17 on NSCLC by examining the association between IL-17A genetic polymorphisms and the susceptibility to NSCLC. IL-17A -420A/G and IL-17A -73G/A polymorphisms were detected in 330 NSCLC patients and 382 healthy controls. We found that subjects carrying -73GA genotype or AA genotype had 2.09-fold or 2.52-fold increased risk of NSCLC than those with -73GG genotype [odds ratio (OR) = 2.09, 95% confidence interval (CI), 1.46 - 2.98, p < 0.001; OR = 2.52, 95% CI, 1.30-4.88, p = 0.005, respectively). However, the IL-17A -420A/G did not reveal any correlation with the cancer. Further investigation showed that prevalence of IL-17A -73GA genotype and A allele were significantly increased in adenocarcinoma patients (OR = 1.75, 95% CI, 1.08-2.86, p = 0.024, OR = 1.57, 95% CI, 1.09-2.28, p = 0.016, respectively). We also evaluated the effect of the polymorphisms on gene expression, and identified that peripheral blood mononuclear cells with IL-17A -73GA and AA genotypes produced significantly higher level of IL-17 than the cells with IL-17A -73GG genotype. Our results suggest that IL-17A -73G/A genetic variations may upregulate IL-17 expression and are associated with increased susceptibility to NSCLC.