Functional interleukin-21 polymorphism is a protective factor of diffuse large B-cell lymphoma.

Interleukin-21 (IL-21) is a recently discovered cytokine and plays critical roles in antitumor immune responses. Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. In this study, we investigated the association between IL-21 genetic polymorphisms and the susceptibility to DLBCL, and the possible functions of these polymorphisms. Two IL-21 polymorphisms, rs907715G/A and rs2221903A/G, were examined in 212 DLBCL patients and 232 healthy controls. Data showed that percentages of rs907715GA and AA genotypes were significantly lower in patients than in controls (odds ratio [OR]=0.60, 95% confidence interval [CI]: 0.40-0.90, p=0.014; OR=0.31, 95% CI: 0.17-0.56, p<0.001, respectively). Frequency of the rs2221903A/G polymorphism did not reveal any significant differences between patients and healthy donors. Further analyses demonstrated a significantly decreased number of rs907715AA genotype in patients with advanced Ann Arbor stages (III+IV). Moreover, we investigated the correlation between IL-21 polymorphisms and serum level of IL-21. Results showed that subjects carrying rs907715AA had significantly increased level of IL-21 than those with GG genotype or GA genotype. These data suggest that rs907715G/A polymorphism may act as a protective factor of DLBCL and might affect the serum level of IL-21.