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Background/aims: In this study, we determined the genotypic and allelic frequencies of the Interleukin (IL)-10(-1082G/A) IL-10(-592A/C), and IL-10(-819C/T) polymorphisms, and their association with the risk to develop B cell Non Hodgkin Lymphoma (NHL) in hepatitis virus C (HCV) carriers., Results: Genetic polymorphisms in the IL-10 gene promoter were studied in 250 consecutive patients with B-cell NHL with no clinical and/or laboratory findings of cryoglobulinemia, 142 NHL/HCV- and 108 NHL/HCV+ with chronic hepatitis (CH), 120 consecutive subjects with HCV-related CH, and 110 age, sex-matched healthy blood donors. The frequency of the IL-10(-1082GG) genotype vs remaining genotypes (IL-10(-1082GA/AA)) was higher in NHL/HCV+ patients than HCV-related CH patients (P=0.0002, OR=2.89, CI: 1.62-5.15) and in NHL/HCV+ than NHL/HCV- patients (P=0.0001, OR=2.99, CI: 1.72-5.19). Moreover, the IL-10(-1082GG) genotype was more prevalent in indolent NHL/HCV+ cases than aggressive NHL/HCV+ (P=0.0004, OR=4.97, CI: 2.10-11.79). Finally, we confirmed that IL-10(-1082GG) genotype is associated with higher IL-10 production compared to AA homozygous (P=0.037)., Conclusions: The high IL-10 production, due to IL-10(-1082GG) genotype, influences the clinical expression of the HCV infection by increasing susceptibility to develop NHL and might contribute to the indolent form of the disease.