Genetic association of interleukin-10 promoter polymorphisms and susceptibility to diffuse large B-cell lymphoma: a meta-analysis.

Published data on the association between interleukin-10 (IL-10) gene polymorphisms and diffuse large B-cell lymphoma (DLBCL) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed, focusing on four major IL-10 gene variants in the promoter region: -3575T/A, -1082A/G, -819C/T and -592C/A. We applied the false discovery rate (FDR) method to adjust for multiple testing. A significant association between IL-10 -3575T/A polymorphism and the risk of DLBCL was observed in the pooled 10 case-control studies (A vs. T: OR=1.16, 95% CI=1.08-1.25, P<0.0001; AA+TA vs. TT: OR=1.20, 95% CI=1.08-1.33, P=0.0009; AA vs. TA+TT: OR=1.25, 95% CI=1.09-1.44, P=0.001). The results indicated that carriers of -1082G allele (-1082GG/GA genotypes) had a nearly 30% increased risk of DLBCL, as compared with carriers of -1082AA genotype (GG+GA vs. AA: OR=1.30, 95% CI=1.08-1.57, P=0.005). When P-values were not adjusted for multiple testing, the risk was significantly decreased among people with -592AA genotype (AA vs. AC+CC: OR=0.63, 95% CI=0.43-0.94, P=0.02), while carriers with -819TT genotype also modestly weakened the DLBCL susceptibility at a marginal level of significance (TT vs. CT+CC: OR=0.59, 95% CI=0.35-0.99, P=0.05). However, these associations were not significant after correction for multiple testing. This meta-analysis suggests that IL-10 -3575A allele confers a greater risk to DLBCL susceptibility, while -1082A/G polymorphism also has significant association with DLBCL risk. These results may help to further clarify the malignancy-risk gene signature of DLBCL, and thus have prognostic and predictive value especially for early-stage DLBCL.