Interleukin-10 gene promoter polymorphisms influence the clinical outcome of diffuse large B-cell lymphoma

Abstract

The aim of the study was to investigate whether interleukin-10 (IL-10) genetic polymorphisms influence this cytokine production as well as the incidence and outcome of diffuse large B-cell lymphoma (DLBCL). The frequency of IL-10_-1082G allele was found to be higher in 199 patients with DLBCL as compared with 112 control subjects (0.47 versus 0.39, P = .043). Increased serum levels of IL-10 were associated with adverse prognostic factors and poor DLBCL outcome. The frequencies of IL-10_-819T and IL-10_-592A alleles were lower in patients with elevated IL-10 serum levels (0.155 versus 0.32, P = .14). As compared with patients carrying the IL-10_-1082AA genotype, patients with the IL-10_-1082G allele (IL-10_-1082GG/GA genotypes) had higher complete remission rate (78% [confidence interval (CI), 71%-85%] versus 65% [CI, 52%-78%], P = .07), 5-year freedom from progression (FFP) (60% [CI, 52%-68%] versus 40% [CI, 27%-53%], P = .013), and overall survival (OS) (63% [CI, 55%-71%] versus 33% [CI, 20%-45%], P = .0009). Among factors of the International Prognostic Index, IL-10_-1082G allele remained an independent variable, predicting longer freedom from progression (FFP) (RR [relative risk] = .76, P = .00035) and OS (RR = .78, P = .0015). These results indicate that IL-10 production contributes to the clinical course of DLBCL and that this phenomenon involves a substantial genetic component. (Blood. 2004;103:3529-3534)