Original Article

International Journal of Clinical Oncology

, Volume 19, Issue 1, pp 186-192

First online:

Association of interleukin-10, tumor necrosis factor-α and transforming growth factor-β gene polymorphisms with the outcome of diffuse large B-cell lymphomas

  • Olivera TarabarAffiliated withClinic of Hematology, Military Medical Academy Email author 
  • , Bojana Cikota-AleksićAffiliated withInstitute for Medical Research, Military Medical Academy
  • , Ljiljana TukićAffiliated withClinic of Hematology, Military Medical Academy
  • , Nenad MilanovićAffiliated withInstitute of Oncology and Radiology
  • , Aleksandar AleksićAffiliated withInstitute of Occupational Health, Military Medical Academy
  • , Zvonko MagićAffiliated withInstitute for Medical Research, Military Medical Academy

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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)-α308 and transforming growth factor (TGF)-β Leu10Pro gene polymorphisms with clinical characteristics and outcome of DLBCL patients treated with rituximab–CHOP therapy.


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.


Patients presenting with B symptoms had IL-103575 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-α308 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).


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-α308 AG/AA genotypes showed a significantly less favorable survival than the GG genotype.


Diffuse large B-cell lymphoma Interleukin-10 Tumor necrosis factor-α Transforming growth factor-β Gene polymorphism