Polymorphisms in cytokine genes as prognostic markers in diffuse large B cell lymphoma patients treated with (R)-CHOP

Ann Hematol. 2017 Feb;96(2):227-235. doi: 10.1007/s00277-016-2857-x. Epub 2016 Nov 7.

Abstract

To investigate whether cytokine genetic polymorphisms influence the outcome of diffuse large B cell lymphoma (DLBCL), we tested 337 consecutive DLBCL treated with CHOP or rituximab-CHOP (R-CHOP) from interleukin 10 (IL10), Bcl-2, and tumor necrosis factor (TNF)-α polymorphisms. Patients who carried the IL10 rs1800871 TT or rs1800872 AA genotype showed higher complete response (CR) and overall response rate (ORR) significantly. A longer progression-free survival (PFS) was observed in patients with IL10 rs1800871 TT (P = 0.017) or rs1800872 AA (P = 0.017) genotype after rituximab-based chemotherapy, and better PFS was also noted with Bcl-2 rs1801018 AA genotype in the CHOP group (P = 0.048). Furthermore, the R-CHOP group patients who carried the IL10 non-CCA haplotype had longer PFS (P = 0.030). Cox proportional hazards analyses demonstrated that the genotype TT of IL10 rs1800871 and AA plus AC of rs1800872 were predictive of longer PFS and event-free survival (EFS) in DLBCL patients treated with R-CHOP. And the Bcl-2 rs2279115 AA plus AC genotypes and rs1801018 GG genotype were risk factors for EFS in DLBCL patients treated with CHOP. In conclusion, the results reminded us those DLBCL patients with IL10 rs1800871 TT, rs1800872 AA, or IL10 non-CCA haplotype are likely to benefit from the therapy of rituximab-based chemotherapy.

Keywords: Cytokine genes; Diffuse large B cell lymphoma; Prognosis; Rituximab.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Cyclophosphamide / therapeutic use
  • Cytokines / genetics*
  • Doxorubicin / therapeutic use
  • Female
  • Haplotypes / genetics
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Prednisone / therapeutic use
  • Rituximab
  • Treatment Outcome
  • Vincristine / therapeutic use
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Biomarkers, Tumor
  • Cytokines
  • R-CHOP protocol
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone