Effect of Cytokine Genes in the Pathogenesis and on the Clinical Parameters for the Treatment of Multiple Myeloma

Abstract

In this study, we aimed to explore the association among gene variants of five cytokines, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta-1 (TGF-beta 1), interferon gamma (IFN-gamma), interleukin-6 (IL-6), and interleukin-10 (IL-10), and clinical parameters and prognosis in patients with multiple myeloma (MM) treated with novel therapeutic drugs in Turkish population for the first time except TNF-alpha. We analyzed five cytokine genes in 113 cases with MM and 113 healthy controls. Cytokine genotyping was performed by the polymerase chain reaction-sequence-specific primer method (PCR-SSP). AG genotype associated with high expression in TNF-alpha gene (-308) variant was found to be significantly higher (p = 0.019), and GG genotype associated with low expression in TNF-alpha gene (-308) variant was significantly lower in MM group as compared with controls (p = 0.012). IFN-gamma (+874) variant TT genotype was increased (p = 0.037), and AA genotype was decreased (p = 0.002) in MM group in contrast to controls. IFN-gamma (+874) T allele was higher inMMpatients compared with controls (OR = 1.985, p = 0.000), while A allele was significantly lower (OR = 0.5037, p = 0.0005). Multivariate analysis revealed that factors associated with 5-year overall survival (OS) were only IPI III (RR = 1.630, p = 0.018) and thrombocytopenia (RR = 2.207, Cox p = 0.021), while 5-year event-free survival (EFS) was associated with IPI III (RR = 1.524, p = 0.022), thrombocytopenia (RR = 2.902, p = 0.002), APSCT treatment (RR = 1.729, p = 0.035), and female gender (RR = 0.435, p = 0.002) with negative prognostic values. Our results suggested that TNF-alpha gene (-308) AG genotype and IFN-gamma (+874) TT genotype and T allele may have a role on MM, while other cytokines were not associated with the risk of MM.