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Annals of Oncology Advance Access originally published online on May 11, 2007
Annals of Oncology 2007 18(8):1376-1381; doi:10.1093/annonc/mdm132
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© 2007 European Society for Medical Oncology

hematologic malignancies

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

S Hohaus*, M Giachelia, A Di Febo, M Martini, G Massini, B Vannata, F D'Alo', F Guidi, M Greco, F Pierconti, LM Larocca, MT Voso and G Leone

Istituto di Ematologia e di Anatomia Patologica, Universita' Cattolica S. Cuore, Rome, Italy

* Correspondence to: Dr Stefan Hohaus, Istituto di Ematologia, Universita' Cattolica S. Cuore, L.go A. Gemelli, 1, 00168 Roma, Italy. Tel: +39-06-30154180. Fax: +39-06-35503777. E-mail: stefan.hohaus{at}rm.unicatt.it

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 nucleotide 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-1082G and C-592A), IL-6 (G-174C) and tumor necrosis factor-{alpha} (C-863A and G-308A) in 184 patients with HL, and analyzed for associations with treatment outcome.

Results: Carriers of the IL-10-592AA 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% CI (confidence interval) 1.58–5.41, P = 0.001] and of 1.75 (95% CI 1.04–2.92, P = 0.03), respectively. Reconstructing haplotypes from the five SNPs in the IL-10 promoter revealed that homozygous carriers of the IL-10.4 haplotype (T-G-C-A-A) had a worse FFTF (HR, 2.35; 95% CI 1.2–4.6, P = 0.01). In the Cox multivariate analysis, the IL-10-592AA, 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.

Key words: cytokine genes, Hodgkin's lymphoma, IL-10, polymorphism, prognosis

Received for publication November 13, 2006. Revision received March 15, 2007. Accepted for publication March 21, 2007.


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