Institute and Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Mol Biol Rep. 2020 May;47(5):3361-3368. doi: 10.1007/s11033-020-05408-4. Epub 2020 Apr 4.
The cell division cycle 25 (CDC25) gene members, including CDC25A, CDC25B and CDC25C, are reported to be associated with several human cancers. Here, we aim to investigate the association of functional polymorphisms of CDC25 gene family with the risk of hepatocellular carcinoma (HCC) and persistent infection of Hepatitis B virus (HBV) in a Chinese HBV-related population. First, we used bioinformatics tools to systematically screen functional polymorphisms within CDC25 gene family. Second, we evaluated the effects of candidate polymorphisms by recruiting 790 HCC cases, 709 persistent HBV carriers (PHC), and 741 subjects with HBV natural clearance (SHNC). MassARRAY platform was used for genotyping. At last, we conducted functional prediction and assay to further explore the pathogenic mechanism of the identified polymorphism. Our results demonstrated that CDC25B rs2295348 played a protective role in HCC risk in a HBV-related Chinese population (adjusted odds ratio [OR] = 0.77, 95% confidence interval [CI] 0.65-0.93, P = 0.006). It showed a more significantly reduced HCC risk in the SHNC population (adjusted OR = 0.73, 95% CI 0.59-0.89, P = 0.002). However, we did not observe the association between CDC25B rs2295348 and the risk of persistent HBV infection. Further functional prediction and assay demonstrated that the mutant A allele of CDC25B rs2295348 might significantly decrease gene expression to modify the HCC risk. Our results suggest that CDC25B rs2295348 may confer a protective effect on HCC risk in a HBV-related Chinese population, but do not influence the susceptibility to persistent HBV infection.
细胞分裂周期 25（CDC25）基因成员，包括 CDC25A、CDC25B 和 CDC25C，据报道与多种人类癌症有关。在这里，我们旨在研究 CDC25 基因家族的功能多态性与乙型肝炎病毒（HBV）相关中国人群中肝细胞癌（HCC）的风险和持续性感染之间的关系。首先，我们使用生物信息学工具系统地筛选了 CDC25 基因家族内的功能多态性。其次，我们通过招募 790 例 HCC 病例、709 例持续性 HBV 携带者（PHC）和 741 例 HBV 自然清除（SHNC）受试者来评估候选多态性的影响。MassARRAY 平台用于基因分型。最后，我们进行了功能预测和检测，以进一步探讨鉴定多态性的致病机制。我们的研究结果表明，在 HBV 相关的中国人群中，CDC25B rs2295348 降低 HCC 风险（校正比值比 [OR] = 0.77，95%置信区间 [CI] 0.65-0.93，P = 0.006）。在 SHNC 人群中，它显示出更显著降低 HCC 风险（校正 OR = 0.73，95%CI 0.59-0.89，P = 0.002）。然而，我们没有观察到 CDC25B rs2295348 与持续性 HBV 感染风险之间的关联。进一步的功能预测和检测表明，CDC25B rs2295348 的突变 A 等位基因可能显著降低基因表达，从而改变 HCC 风险。我们的研究结果表明，CDC25B rs2295348 可能对 HBV 相关的中国人群中的 HCC 风险具有保护作用，但不影响对持续性 HBV 感染的易感性。
