Abstract

Lung cancer is known to be a complex multifactorial disease involving both genetic and environmental factors. The study of different signaling pathways and identification of the genes involved, will contribute to further understanding the pathogenesis of the disease, thus allowing the development of appropriate targeted treatments and even a prevention strategies. The inflammation caused by immune system activation is likely linked to carcinogenesis by promoting angiogenesis and proliferation of tumour cells, according to the cytokine profile in the tumour microenvironment. Previous studies have suggested that key cytokines in inflammation pathways may have an important roles in the etiology of lung cancer. The aim of this study was to investigate whether common inflammation related genes influence lung cancer risk in Moroccan population. Single nucleotide polymorphisms (SNPs) in IL-6, IL6-R and IL6-ST, IL6, IL17-A, IL17-F, IL-8, MIF and STAT3 genes were assessed in 150 controls and 150 lung cancer patients. Genotyping was performed with the TaqMan® allelic discrimination technology and RFLP-PCR. Gene expression of cytokines was evaluated in the peripheral blood samples of lung cancer patients and healty controls. Total RNA of the blood cells were extracted and reverse transcribed to cDNA. Screenings of deferentially expressed genes associated with inflammation were performed using real-time PCR. Among the studied SNPs, we found a significant association for the IL-6 (rs2069840), IL-6 (rs1800795), IL-6 (rs1800796), IL-17F (rs763780), IL-17F (rs763780), IL-8 and the MIF (rs755622). No significant association was observed for the remaining SNPs of IL-6R (rs2228145) IL-6ST (rs2228044), IL-17A (rs2275913), IL17A (rs7747909) and STAT3 (rs2293152) genes. Cytokines genes expression revealed significant association with lung cancer. Genes expression were increased in lung cancer patients comparing to healthy subjects. Our results suggest the important role of inflammation related genes in the occurrence of lung cancer and cytokines genes associated may be considered as a genetic marker for predisposition to Lung cancer in Moroccan population.

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