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

Immunol Invest. 2017 Jan;46(1):10-21. doi: 10.1080/08820139.2016.1208219. Epub 2016 Sep 9.

Abstract

In this study, we aimed to explore the association among gene variants of five cytokines, tumor necrosis factor alpha (TNF-α), transforming growth factor beta-1 (TGF-β1), interferon gamma (IFN-γ), 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-α. 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-α gene (-308) variant was found to be significantly higher (p = 0.019), and GG genotype associated with low expression in TNF-α gene (-308) variant was significantly lower in MM group as compared with controls (p = 0.012). IFN-γ (+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-γ (+874) T allele was higher in MM patients 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-α gene (-308) AG genotype and IFN-γ (+874) TT genotype and T allele may have a role on MM, while other cytokines were not associated with the risk of MM.

Keywords: Cytokine gene expression; multiple myeloma; prognostic factors.

MeSH terms

  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Interferon-gamma / genetics*
  • Interleukin-10 / genetics*
  • Interleukin-6 / genetics*
  • Male
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / mortality
  • Sex Factors
  • Survival Analysis
  • Thrombocytopenia / genetics*
  • Thrombocytopenia / mortality
  • Transforming Growth Factor beta1 / genetics*
  • Tumor Necrosis Factor-alpha / genetics*
  • Turkey

Substances

  • Interleukin-6
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma