CDC25B is associated with the risk of hepatocellular carcinoma, but not related to persistent infection of hepatitis B virus in a Chinese population

• Published in: Molecular biology reports Vol. 47; no. 5; pp. 3361 - 3368
• Main Authors: Wang, Peng, Peng, Jing, Gong, Yajie, Shen, Na
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.05.2020; Springer Nature B.V
• Subjects: Alleles; Animal Anatomy; Animal Biochemistry; Asian Continental Ancestry Group - genetics; Bioinformatics; Biomedical and Life Sciences; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Case-Control Studies; cdc25 Phosphatases - genetics; cdc25 Phosphatases - metabolism; Cdc25B phosphatase; Cell division; China - epidemiology; chronic diseases; confidence interval; Gene expression; Gene Frequency - genetics; Genetic Predisposition to Disease - genetics; Genotype; Genotyping; Haplotypes - genetics; Hepatitis B; Hepatitis B - epidemiology; Hepatitis B - genetics; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - pathogenicity; Hepatitis B, Chronic - genetics; Hepatocellular carcinoma; hepatoma; Histology; Humans; Infections; Life Sciences; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; molecular biology; Morphology; mutants; odds ratio; Original Article; Persistent infection; Polymorphism, Single Nucleotide - genetics; Population; prediction; protective effect; risk; China; Risk; Persistent HBV infection; Hepatocellular carcinoma (HCC); Polymorphism; CDC25B
• ISSN: 0301-4851; 1573-4978; 1573-4978
• DOI: 10.1007/s11033-020-05408-4

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.