Prognostic importance of single-nucleotide polymorphisms in IL-6, IL-10, TGF-beta 1, IFN-gamma, and TNF-alpha genes in chronic phase chronic myeloid leukemia

The aim of this study was to explore the association between polymorphisms of five cytokine genes and clinical parameters in patients with Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) treated with imatinib. We analyzed five cytokine genes (interleukin [IL]-6, IL-10, gamma interferon [IFN-gamma], transforming growth factor beta-1 [TGF-beta 1], and tumor necrosis factor-alpha [TNF-alpha]) in 60 cases with Ph+ CML and 74 healthy controls. Cytokine genotyping was performed by the polymerase chain reaction-sequence-specific primer. All data were analyzed using the de Finetti program and SPSS version 14.0 for Windows. No significant differences were detected between the CML group and healthy controls with respect to the distributions and numbers of genotypes and alleles in TNF-alpha, TGF-beta 1, IL-10, and IFN-gamma. However, the GG genotype associated with high expression in IL-6 was found to be significantly more frequent in CML as compared to controls (p = 0.010). The median follow-up time was 49.3 months (range 6.1-168.4) and the median duration of imatinib treatment was 39.5 months (range 5.2-103.4) for these patients. On multivariateanalysis, only IL-10 GCC/GCC highly produced haplotypes were significantly associated with a shorter event-free survival. The relationship between cytokine genotypes/haplotypes and clinical parameters in CML has not been investigated before. Our results suggest that IL-10 may be a useful marker for CML prognosis and theGG genotype of the IL-6 gene may be associated with susceptibility.