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IL-21 gene polymorphism is associated with the prognosis of breast cancer in Chinese populations

  • Epidemiology
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Abstract

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.

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Acknowledgments

This study was supported by the National Natural Scientific Foundation of China grants 81001278, 81171895, and 81072366; A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, Jiangsu Provincial Natural Science Foundation (No. BK2011297) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (No. 20101561).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, 215123, China

    Yonghe You, Jieqiong Deng, Jian Zheng, Na Li, Hongchun Wu, Wei Li & Yifeng Zhou

  2. Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China

    Min Hu

  3. The Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, 510182, China

    Jiachun Lu

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  1. Yonghe You
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Correspondence to Yifeng Zhou.

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Yonghe You and Jieqiong Deng contributed equally to this work.

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You, Y., Deng, J., Zheng, J. et al. IL-21 gene polymorphism is associated with the prognosis of breast cancer in Chinese populations. Breast Cancer Res Treat 137, 893–901 (2013). https://doi.org/10.1007/s10549-012-2401-1

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