Abstract 919: The influence of haplotype of interleukin-10 gene on the susceptibility and clinical outcome of non-Hodgkin lymphoma

Background: Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and single-nucleotide polymorphisms (SNP) of this gene have been reported to affect transcription and production of IL-10. Although the association between SNP and Non-Hodgkin lymphoma (NHL) and increased serum IL-10 levels in NHL patients than controls have been known, there were a few reports in context of haplotypes of whole IL-10 gene. In this study, we investigated the association between haplotype of IL-10 gene and the risk of NHL. Moreover, we investigated the association between IL-10 haplotype, and the overall survival and prognostic factors. Methods: A total of 209 NHL patients and 418 sex- and age- matched controls was included in this study. Through database searching 4 tagging SNPs covering 2.6 kb of IL-10 gene (rs3021094, rs1554286, rs1800872, and rs1800896) were selected considering ethnicity. Analysis was done using TaqMan probe or sequencing. Haplotype and linkage disequilibrium (LD) was analyzed by PHASE and Haploview program. We compared each genotype or haplotype frequency in controls with that in patients. Genotype was tested for its association with overall survival, clinical characteristics (e.g., cell lineage) and international prognostic indices including age, performance, LDH, stage and extra-nodal involvement. Results: All studied SNP were in Hardy-Weinburg equation in controls. There is no strong LD between four SNPs with r2 ranged from 0.002 to 0.211. Among 15 haplotypes identified by PHASE analysis, haplotype 1 (Ht1, TATT at rs3021094, rs1554286, rs1800872, and rs1800896) composed with all of dominant polymorphisms showed a significantly increased risk for developing NHL with odds ratios (OR) of 2.08 [95% confidence interval (CI); 1.47-2.96] and 5.17 [95% CI; 2.45-10.93] in single or both allele carrier of Ht1 than other haplotypes. There was no significant association between the haplotype of IL-10 and risk factors of NHL. Furthermore, Ht1 was shown to be associated with a significantly worse overall survival in patients with diffuse large B cell lymphoma (DLBCL) with CHOP (cyclophosphamide, adriamycin, vincristine and prednisone, n=37) chemotherapy done before introduction of rituximab therapy (p=0.04), while not significant in patients treated by R-CHOP (Rituximab plus CHOP, n=86) chemotherapy (p=0.27). Conclusions: This study showed that the IL-10 haplotype is a susceptibility marker for the development of NHL, and it was a significant prognostic in