Int J Clin Oncol 2014 Feb 27;19(1):186-92. Epub 2013 Mar 27.
Clinic of Hematology, Military Medical Academy, Crnotravska 17, 11000, Belgrade, Serbia,
Background: Published data indicate that common genetic variants in immune/inflammatory response genes can affect the outcome of diffuse large B-cell lymphomas (DLBCL). This study investigated the association of interleukin (IL)-10 (-3575, -1082), tumor necrosis factor (TNF)-α -308 and transforming growth factor (TGF)-β Leu10Pro gene polymorphisms with clinical characteristics and outcome of DLBCL patients treated with rituximab-CHOP therapy.
Methods: Between January 2004 and December 2007, a total of 84 patients with newly diagnosed DLBCL entered into this study. Genotypes were determined with PCR-based methodology.
Results: Patients presenting with B symptoms had IL-10 -3575 TA/AA genotypes more frequently than TT genotype [odds ratio (OR) 2.89, 95 % confidence interval (CI) 1.11-7.57; p = 0.03]. Carriers of TGF-β Pro10 allele more frequently had an advanced clinical stage III/IV (OR 4.65, 95 % CI 1.33-16.19; p = 0.016) and intermediate-high/high IPI score (OR 5.37, 95 % CI 1.45-20.0; p = 0.012). In rituximab-CHOP-treated patients (n = 64), the TNF-α -308 AG/AA carriers had shorter overall (p = 0.048) and event-free survival (p = 0.07) compared to GG carriers. In multivariate analysis of prognostic factors for survival, the TNF-α AG/AA genotypes were significantly associated with inferior survival of lymphoma patients (OR 0.23, 95 % CI 0.07-0.78; p = 0.018).
Conclusion: Our results indicate the association of IL-10 -3575 and TGF-β Leu10Pro gene variations with clinical characteristics. In patients treated with rituximab-CHOP therapy, the TNF-α -308 AG/AA genotypes showed a significantly less favorable survival than the GG genotype.