The role of gene polymorphisms and gene expression of cytokines (tumour necrosis factor alfa (RNF-α), transforming growth factor beta-1 (TGF-β1), interferon gamma (İFN-Y), interleukin-6 (IL-6), and interleukin-10 (IL-10)) in the etiopathogenesis of the disease, clinical parameters and prognosis in hl patients

Background and aim: In Hodgkin Lymphoma (HL), Reed-Sternberg (RS) cells play a role in the etiopathogenesis and clinical course of the disease and that is thought to be the result of expression of cytokines. In this study; it was aimed to evaluate the role of gene polymorphisms and gene expression of five cytokines (tumour necrosis factor alfa (TNF-α), transforming growth factor beta-1 (TGF-β1), interferon gamma (IFN-γ), interleukin-6 (IL-6), and interleukin-10 (IL-10)) in the etiopathogenesis of the disease, clinical parameters and prognosis in HL patients. Methods:A total of 70 patients and 70 control group who were diagnosed, treated and followed up for HL in the Hematology clinic of Gaziantep University Faculty of Medicine were included in the study. Cytokine gene polymorphisms and expression levels were analyzed by DNA isolation from peripheral blood of the patient and control groups and by using of Sequence Specific Primary polymerase chain reaction (PCR-SSP) method. Results:TNF-α (-308) gene variant GA genotype (high expression), IFN-γ (+874) gene variant TT genotype (high expression), IL6 (-174) gene variant GG genotype (high expression), TGF-β1 (T10/C10) gene variant TT genotype, TGF-β1 (C25/G25) gene variant GC genotype, IL10 (-1082) gene variantGG genotype, IL10 (-819) gene variantCC genotype and IL10 (-592) gene variantCC genotype was significantly higher in HL patients compared to healthy controls (respectively; OR= 0.3636, p= 0.0259; OR= 0.3164, p= 0.0349, OR= 0.4189, p = 0.0299, OR= 0.4329, p= 0.0257, OR= 0.4889, p<0.001, OR= 0.4189, p= 0.0299, OR= 0.3951, p= 0.0193, OR= 0.3951, p= 0.0193). While IL6 (-174) G allele (p = 0.0302), TGF-β1 (T10 / C10) T allele (p = 0.0224), IL10 (-1082) G allele (p = 0.0232), IL10 (-819) C allele (p = 0.0156), IL10 (-592) C allele (p = 00156) was higher in HL patients compared to the control group, expression of IL6 (-174) C allele (p = 0.0302), TGF-β1 (T10 / C10) C allele (p = 0.0224), IL10 (-1082) A allele (p = 0.0232), IL10 (-819) T allele, IL10 (-592) A allele (p = 0.0156) was found to be low. In haplotype analysis; TGF-β1 (T / C10, C / G25) gene "TCGC, CCGG, TTGC" (moderately increased plasma TGF-β1 level) and IL10 (-1082, -819, -592) gene "GCC GCC" (high IL10 plasma level) haplotype variants was significantly higher in HL patients than in the control group (respectively; OR= 0.3406, p= 0.0161; OR= 0.4149, p= 0.0299).In multivariate analysis; Bone marrow involvement (p <0.001) and carrier of IL6 (-174) gene polymorphism CC variant genotype (p= 0.02) were detected as an independent risk factor associated with poor prognosis on 5-year PFS. Conclusion:The results of the studysuggests that TNF-α (-308) GA genotype, IFN-γ (+874) TT genotype, IL6 (-174) GG genotype, TGF-β1 (T10 / C10) TT genotype, TGF-β1 (C25 / G25) GC genotype, IL10 (-1082) GG genotype, IL10 (-819) CC genotype, IL10 (-592) CC genotype, TGF-β1 (T / C10, C / G25) gene "TCGC, CCGG, TTGC" and IL10 (-1082, -819, -592) gene "GCC GCC" haplotype may be a risk factor for HL development. Keywords: Cytokine gene polymorphism, Hodgkin lymphoma, prognostic factors