Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, China.
Breast Cancer Res Treat. 2013 Feb;137(3):893-901. doi: 10.1007/s10549-012-2401-1. Epub 2013 Jan 4.
Interleukin (IL)-21, which is secreted by activated CD4(+) T cells and NKT cells, has been found to be able to influence the humoral and cell-mediated immune responses and have potent antitumor activity in animal models. This study was to investigate the impact of genetic polymorphisms in IL-21 on survival of breast cancer. Four TagSNPs of IL-21 (rs12508721C>T, rs907715G>A, rs13143866G>A, rs2221903A>G) were selected and then genotyped in 891 patients with breast cancer in Eastern and Southern Chinese populations. We then examined the associations between these SNPs and overall survival. Potential function of rs12508721C>T and association between this variation and breast cancer prognosis were further studied. Overall, 121 of the patients had died over the followed-up period of 5 years. The IL-21 rs12508721T allele predicted longer five-year survival (HR = 0.347, 95 % CI = 0.187-0.644, P < 0.0001) in the discovery cohort, the independent validation cohort (HR = 0.429, 95 % CI = 0.244-0.755, P = 0.012), and combined group (HR = 0.447, 95 % CI = 0.301-0.667, P < 0.0001). Furthermore, our luciferase assay revealed that rs12508721T variant allele had a higher transcription activity and the RT-PCR and ELISA assay showed that rs12508721 variant genotypes (CT and TT) carriers have more IL-21 expression than CC carriers (P < 0.05). Our present study established a robust association between the functional polymorphism (rs12508721C>T) in IL-21 and prognosis of breast cancer, indicating that this polymorphism may be a potential biomarker for prognosis of breast cancer.
白细胞介素（IL）-21 由活化的 CD4（+）T 细胞和 NKT 细胞分泌，已被发现能够影响体液和细胞介导的免疫反应，并在动物模型中具有强大的抗肿瘤活性。本研究旨在探讨 IL-21 基因多态性对乳腺癌患者生存的影响。选择 IL-21 的四个 TagSNP（rs12508721C>T、rs907715G>A、rs13143866G>A、rs2221903A>G），然后对东方和南方中国人群中的 891 例乳腺癌患者进行基因分型。然后，我们检查了这些 SNP 与总生存之间的关联。进一步研究了 rs12508721C>T 与总体生存的潜在功能以及这种变异与乳腺癌预后之间的关系。在随访的 5 年内，共有 121 例患者死亡。IL-21 rs12508721T 等位基因预测发现队列（HR=0.347，95%CI=0.187-0.644，P<0.0001）、独立验证队列（HR=0.429，95%CI=0.244-0.755，P=0.012）和联合组（HR=0.447，95%CI=0.301-0.667，P<0.0001）中五年生存率更长。此外，我们的荧光素酶报告基因检测显示，rs12508721T 变异等位基因具有更高的转录活性，RT-PCR 和 ELISA 检测显示，rs12508721 变异基因型（CT 和 TT）携带者的 IL-21 表达高于 CC 携带者（P<0.05）。本研究建立了 IL-21 功能多态性（rs12508721C>T）与乳腺癌预后之间的稳健关联，表明该多态性可能是乳腺癌预后的潜在生物标志物。
