RESUMO
To date, several studies have reported that key cytokines in the inflammatory system have important roles in the pathogenesis of cancer, notably in lung cancer. The aim of this case-control study, conducted for the first time in Moroccan population, was to investigate and to analyze the association of the following inflammatory cytokine genes Interleukin (IL)-6, Interleukin (IL)-8, Interleukin (IL)-10, Interleukin (IL)-17, Tumor Necrosis Factor-Alpha (TNFA), Macrophage migration Inhibitory Factor (MIF) and Signal Transducer and Activator of Transcription 3 (STAT3) with lung cancer risk in our patients. Firstly, the mRNA expression was assessed by a quantitative real time PCR in the peripheral blood of lung cancer patients and healthy subjects. Secondly, polymorphisms in the genes encoding cytokines were assessed in 160 lung cancer patients and 150 healthy controls. Genotyping analysis was performed with a Real-Time polymerase chain reaction using TaqMan® genotyping assays on a 7500 FAST Real-Time PCR System and Restriction Fragment Length PolymorphismPCR. Our results revealed a significant difference in mRNA expression levels of IL-6, IL-8, IL-10, IL-17 and TNFA genes in lung cancer patients compared to healthy subjects (P < 0.05). Among the studied genes, we found a significant association between lung cancer risk in our patients and the following polymorphisms IL-6 (rs1800795, rs1800796), IL-8 (rs4075, rs2227306), IL-17F (rs763780, rs2397084) and MIF (rs755622). In conclusion, the results of our study suggest that IL-6, IL-8, IL-10, IL-17 and MIF cytokine genes may aggravate lung cancer risk in the Moroccan population. However, further investigations are required to confirm our findings.
Assuntos
Neoplasias Pulmonares , Fatores Inibidores da Migração de Macrófagos , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Neoplasias Pulmonares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
PURPOSE: Lung cancer is known to be a complex multifactorial disease, involving both genetic and environmental factors. The study of the different signaling pathways and the identification of the genes involved, will contribute to further understanding the pathogenesis of the disease, thus allowing the development of appropriate targeted treatments. Recently, the link between cancer and inflammation has become more evident and inflammation has been proposed as the seventh hallmark of cancer. Previous studies have suggested that key cytokines involved in inflammation may have an important role in the etiology of lung cancer. The aim of this study was to investigate whether common variants in inflammation-related genes: IL-6, IL6-R, and IL6-ST, influence lung cancer risk in Moroccan population. MATERIALS AND METHODS: Single nucleotide polymorphisms (SNPs) in IL-6, IL6-R, and IL6-ST genes were assessed in 120 controls and 120 patients with confirmed lung cancer diagnosis. Genotyping analysis was performed with the TaqMan® allelic discrimination technology. The results were analyzed using SPSS 24.0 software. RESULTS: Among the studied SNPs, we found a significant association for the IL-6 (rs2069840) (OR = 1.63; 95% confidence interval 1.08-2.47; p = 0.01). No significant association was observed for the remaining SNPs of IL-6R (rs2228145) and IL-6ST (rs2228044) genes. CONCLUSION: Our results suggest the IL-6 (rs2069840) polymorphism may influence the occurrence of lung cancer in Moroccan patients.
Assuntos
Interleucina-6/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Receptor gp130 de Citocina/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Marrocos , Fenótipo , Receptores de Interleucina-6/genética , Medição de Risco , Fatores de RiscoRESUMO
The study of EGFR gene mutational profile in NSCLC patients has a special clinical significance in the selection of patients for tyrosine-kinase inhibitors therapy. From 2017, the targeted therapy started to be accessible in public sector in Morocco, thus, the implementation of techniques for the molecular characterization of EGFR mutations in the laboratories became a necessity. The aim of this study was to present targeted methods "ADx-ARMS technology and the Idylla™ system" for the identification of EGFR mutational profile, methods that can be implemented in our clinical laboratories for routine analysis instead of outsourcing analysis to other countries. We conducted this study by processing 239 cases of NSCLC patients. Using the DNA extracted from the FFPE tissue, we evaluated somatic mutations in exons 18 to 21 of the tyrosine-kinase domain of EGFR gene by HRM-PCR combined to real time PCR "ADx-ARMS technology" and Idylla™ system. These sensitive methods showed that among the positive mutant cases, the distribution of mutations was as follows: 70% of patients having a deletion in exon 19, 15% in exon 21 (L858R), 7.5% in exon 20 and 7.5% in exon 18 (G719X). All of the positive EGFR mutations cases were adenocarcinoma and 42.1% of them were smokers. These results show the need to incorporate a quick and efficient method for the identification of EGFR mutation into routine practice in our laboratories, allowing more patients to benefit from targeted therapy.
