Association Between Inflammation And Immune-related Gene Polymorphisms And Non-Hodgkin’s Lymphoma Susceptibility, Treatment Outcome And Prognosis

Objective:We conducted this study to evaluate the association between single nucleotide polymorphisms (SNP) in inflammation and immune-related genes and risk of non-Hodgkin’s lymphoma (NHL), as well as the treatment outcome and prognosis of NHL patients in a Chinese population.Methods:A case-control study of514NHL patients and557cancer-free controls in a Chinese population was conducted. We used the Taqman assay to genotype six functional SNPs in six previously reported inflammation and immune-related genes (TNF rs1799964T>C, LTA rs1800683G>A,IL-10rs1800872T>G, LEP rs2167270G>A, LEPR rs1327118C<G, TNFAIP8rs1045241C>T). Logistic regression models were used to estimate odds ratios (ORs) and95%confidence intervals (95%CI). We further explored the association between these six SNPs and the prognosis of NHL patients. Kaplan-Meier was applied to assess the survival probability, and the differences between two groups were compared by Log-rank test. The multivariate analysis was performed by Cox regression model.Results:1. We observed a significantly increased risk of NHL associated with the TNFAIP8rs1045241C>T polymorphism (adjusted OR=2.03;95%CI=1.53-2.69for CT/TT vs. CC, P<0.001). But we did not find altered NHL risk for variant genotypes of other five SNPs compared with their common homozygous genotypes.2. Subsequent stratification analyses demonstrated that risk for both B and T cell non-Hodgkin’s lymphoma was elevated with CT/TT genotypes (adjusted OR=1.95,95%CI=1.41-2.70for B cell NHL,P=0.002and adjusted OR=2.22,95%CI=1.49-3.30for T cell NHL, P=0.0007), particularly for DLBCL (adjusted OR=2.01,95%CI=1.41-2.85, P=0.002) and FL (adjusted OR=2.53,95%CI=1.17-5.45, P<0.001), but not for NK/T cell lymphoma (adjusted OR=0.79.95%CI=0.27-2.33, P=0.137).3. We also found that LTA rs1800683G>A was associated with the prognosis of DLBCL patients. Compared with the GG/GA genotype, AA genotype carriers showed a worse progression free survival (PFS, P=0.007). But the other5SNPs showed no association with NHL prognosis. Nor did we find any association between SNPs and efficiency of first-line chemotherapy for DLBCL. 4. The multivariate analyses showed that Ann Arbor stage of Ⅲ/Ⅳ(HR=5.04,95%CI=2.34-10.83,P<0.001), elevated LDH level before treatment (HR=3.18,95%CI=1.48-6.83, P=0.003) and LTA rs1800683AA genotype carriers (HR=2.04,95%CI=1.01-4.14, P=0.049) were statistically significant unfavorable independent prognostic factors for DLBCL, while rituximab plus chemotherapy predicted better prognosis. For NK/T cell lymphoma, Ann Arbor stage of Ⅲ/Ⅳ (HR=3.59,95%CI=1.45-8.87,P=0.006) and elevated β2-microglobulin (β2-MG) level (HR=3.73,95%CI=1.37-10.17, P=0.01) were statistically significant unfavorable independent prognostic factors.Conclusions:1. The polymorphism of TNFAIP8rs1045241C>T contributes to NHL susceptibility in a Chinese population. The T allele increased the risk of NHL, particularly DLBCL and FL.2. LTA rs1800683G>A was associated with the prognosis of DLBCL. AA genotype predicted worse PFS.3. Ann Arbor stage of Ⅲ/Ⅳ, elevated LDH level before treatment and LTA rsl800683AA genotype carriers were unfavorable independent prognostic factors for DLBCL, while Rituximab plus chemotherapy predicted better prognosis. For NK/T cell lymphoma, Ann Arbor stage of III/IV and elevated P2-MG level predicted worse prognosis.