IMMUNOLOGICAL INVESTIGATIONS, vol.46, no.1, pp.10-21, 2017 (SCI-Expanded)
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.