Interleukin (IL)-21 promoter polymorphism increases the risk of thyroid cancer in Chinese population

•We explored the role of five tagSNPs in IL-21 gene in thyroid cancer development.•Rs12508721C > T was associated with decreased risk of thyroid cancer.•Rs12508721T allele led to more IL-21 expression to play its antitumor role.

Polymorphisms in Interleukin (IL)-21 have been researched in several cancers, but the association between IL-21 polymorphisms and thyroid cancer remains unclarified. This case-control study explored the role of five tagSNPs (rs12508721C > T, rs907715G > A, rs13143866G > A, rs2221903A > G and rs4833837A > G) in IL-21 gene in thyroid cancer development. IL-21 genotypes were examined in 615 thyroid cancer patients and 600 controls in Chinese population, and the associations with the risk of thyroid cancer were estimated by logistic regression. Moreover, the potential role of rs12508721C > T in thyroid cancer was further explored by biochemical assays. Compared with the rs12508721CC genotype, CT genotype presented a significantly decreased risk of thyroid cancer (adjusted odds ratios [OR] = 0.72; 95%CI = 0.57-0.94), the TT carriers had a further decreased risk of thyroid cancer (OR = 0.56; 95%CI = 0.41-0.87). Furthermore, our quantitative real-time PCR and Enzyme-linked immunosorbent assay (ELISA) results demonstrated that the presence of rs12508721T allele led to more IL-21 expression. However, no significant difference was found in genotype frequencies for other four sites between cases and controls. These findings suggested that rs12508721 polymorphism in IL-21 might be a genetic modifier for the development of thyroid cancer.