IL-21Gene Polymorphism Is Associated With The Prognosis Of Breast Cancer In Chinese Populations

Interleukin (IL)-21, which is secreted by activated CD4+T cells and NKT cells, hasbeen found to be able to influence the humoral and cell-mediated immune responses andhave potent antitumor activity in animal models. This study was to investigate theimpact of genetic polymorphisms in IL-21on survival of breast cancer. Four TagSNPs ofIL-21(rs12508721C>T, rs907715G>A, rs13143866G>A, rs2221903A>G) wereselected and then genotyped in891patients with breast cancer in Eastern and SouthernChinese populations. According to clinical and follow-up data, we then examined theassociations between these SNPs and overall survival. Kaplan-Meier method was usedto plot the survival curves and t and Log-rank test was used to test the difference ofsurvival time. The results revealed that the rs12508721C>T polymorphism in thepromoter region of IL-21gene was significant associated with breast cancer prognosis.Compared to the subjects who harbored IL-21rs12508721CCgenotype, theIL-21rs12508721T allele carriers had longer five-year survival (HR=0.447,95%CI=0.301–0.667, P<0.0001).Biochemical assays were used to examine the functionalrelevance of this polymorphism. The results demonstrated that compared with thers12508721CC genotype, the rs12508721CT or TT genotypes can enhance the transcriptactivity of IL-21. Moreover, the rs12508721variant genotypes (CT and TT) carriershave more IL-21mRNA and protein expression than CC carriers (P<0.05). Furthermore,upon to the stimulation of concanavalin A (Con-A), healthy subjects who harbored thers12508721TT genotype had a higher T-cell proliferation rate than individualsexpressing the rs12508721CC genotype. Our present study established a robustassociation between the functional polymorphism (rs12508721C>T) in IL-21andprognosis of breast cancer, indicating that this polymorphism may be a potentialbiomarker for prognosis of breast cancer. In addition, further functional studies on thesegenetic variants are needed to define the specific role of the IL-21in the pathogenesisand prognosis of other different tumors in Chinese populations or in different ethnicities.