Polymorphism in cytokine genes as prognostic markers in Hodgkin's lymphoma

Background: In Hodgkin's lymphoma (HL), the production of cytokines by Reed-Sternberg cells and the surrounding tissue is thought to contribute to the biology of the disease. Cytokine expression can be altered by common single nucleotice polymorphisms (SNPs) in the 5'-promoter regions.Patients and methods: We studied polymorphic allele variants of the cytokine genes interleukin (IL)-10 (T-3575A, G-2849A, C-2763A, A-1 082G and C-592A), IL-6 (G-1 74C) and tumor necrosis factor-oc (C-863A and G-308A) in 184 patients with HL, and analyzed for associations with treatment outcome.Results: Carriers of the IL-1 0-592AA and the IL-6-174GG genotypes had a significantly lower probability of freedom from treatment failure (FFTF) with adjusted hazard ratios (HRs) for failure of 2.92 [95% Cl (confidence interval) 1.58-5.41, P = 0.001] and of 1.75 (95% Cl 1.04-2.92, P= 0.03), respectively. Reconstructing haplotypes from the five SNPs in the IL-1 0 promoter revealed that homozygous carriers of the IL-1 0.4 haplotype (T-G-C-A-A) had a worse FFFF (HR, 2.35; 95% Cl 1.2-4.6, P = 0.01). In the Cox multivariate analysis, the IL-1 0-592AA, the IL-6-174GG genotypes and stage were independent prognostic factors.Conclusions: Our study indicates that cytokine genotypes predict clinical outcome in patients with HL and points to the importance of the genetic background of the host for treatment response.