title: Association of interleukin-10, tumor necrosis factor-α and transforming growth factor-β gene polymorphisms with the outcome of diffuse large B-cell lymphomas.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinic of Hematology, Military Medical Academy, Crnotravska 17, 11000, Belgrade, Serbia, olivera@tarabar.net.
authors.forename: Olivera
authors.initials: O
authors.lastname: Tarabar
authors.forename: Bojana
authors.initials: B
authors.lastname: Cikota-Aleksić
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Tukić
authors.forename: Nenad
authors.initials: N
authors.lastname: Milanović
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Aleksić
authors.forename: Zvonko
authors.initials: Z
authors.lastname: Magić
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D054316:Biomarkers, Pharmacological; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011241:Prednisone / Q000008:administration & dosage; D000069283:Rituximab; D016212:Transforming Growth Factor beta / Q000235:genetics*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D054316:Biomarkers, Pharmacological; C571759:R-CHOP protocol; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone