Relationships between cell cycle pathway gene polymorphisms and risk of hepatocellular carcinoma

• Published in: World journal of gastroenterology : WJG Vol. 22; no. 24; pp. 5558 - 5567
• Main Authors: Nan, Yue-Li, Hu, Yan-Ling, Liu, Zhi-Ke, Duan, Fang-Fang, Xu, Yang, Li, Shu, Li, Ting, Chen, Da-Fang, Zeng, Xiao-Yun
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 28.06.2016
• Subjects: 14-3-3 Proteins - genetics; Adult; Alcohol Drinking - epidemiology; Carcinoma, Hepatocellular - epidemiology; Carcinoma, Hepatocellular - genetics; carcinoma;Single; Case Control Study; cdc25 Phosphatases - genetics; Cell; Cell Cycle - genetics; Checkpoint Kinase 1 - genetics; China - epidemiology; cycle; Cyclin-Dependent Kinase Inhibitor p18 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Female; Gene-Environment Interaction; genes;Hepatocellular; Genetic Predisposition to Disease; Hepatitis B, Chronic - epidemiology; Humans; Liver Neoplasms - epidemiology; Liver Neoplasms - genetics; Male; Middle Aged; Minichromosome Maintenance Complex Component 4 - genetics; Minichromosome Maintenance Complex Component 7 - genetics; Nuclear Proteins - genetics; nucleotide; p300-CBP Transcription Factors - genetics; pathway; Phosphoproteins - genetics; Polymorphism, Genetic; polymorphism;Casecontrol; Retinoblastoma-Like Protein p130 - genetics; Smad3 Protein - genetics; Smoking - epidemiology; study;G; Transforming Growth Factor beta3 - genetics; Case-control study; Hepatocellular carcinoma; Single nucleotide polymorphism; Genetic susceptibility; Cell cycle pathway genes
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v22.i24.5558

AIM: To investigate the associations between the polymorphisms of cell cycle pathway genes and the risk of hepatocellular carcinoma(HCC). METHODS: We enrolled 1127 cases newly diagnosed with HCC from the Tumor Hospital of Guangxi Medical University and 1200 non-tumor patients from the First Affiliated Hospital of Guangxi Medical University. General demographic characteristics, behavioral information, and hematological indices were collected by unified questionnaires. Genomic DNA was isolatedfrom peripheral venous blood using Phenol-Chloroform. The genotyping was performed using the Sequenom Mass ARRAY i PLEX genotyping method. The association between genetic polymorphisms and risk of HCC was shown by P-value and the odd ratio(OR) with 95% confidence interval(CI) using the unconditional logistic regression after adjusting for age, sex, nationality, smoking, drinking, family history of HCC, and hepatitis B virus(HBV) infection. Moreover, stratified analysis was conducted on the basis of the status of HBV infection, smoking, and alcohol drinking.RESULTS: The HCC risk was lower in patients with the MCM4 rs2305952 CC(OR = 0.22, 95%CI: 0.08-0.63, P = 0.01) and with the CHEK1 rs515255 TC, TT, TC/TT(OR = 0.73, 95%CI: 0.56-0.96, P = 0.02; OR = 0.67, 95%CI: 0.46-0.97, P = 0.04; OR = 0.72, 95%CI: 0.56-0.92, P = 0.01, respectively). Conversely, the HCC risk was higher in patients with the KAT2 B rs17006625 GG(OR = 1.64, 95%CI: 1.01-2.64, P = 0.04). In addition, the risk was markedly lower for those who were carriers of MCM4 rs2305952 CC and were also HBs Ag-positive and non-drinking and nonsmoking(P < 0.05, respectively) and for those who were carriers of CHEK1 rs515255 TC, TT, TC/TT and were also HBs Ag-negative and non-drinking(P < 0.05, respectively). Moreover, the risk was higher for those who were carriers of KAT2 B rs17006625 GG and were also HBs Ag-negative(P < 0.05).CONCLUSION: Of 12 cell cycle pathway genes, MCM4, CHEK1 and KAT2 B polymorphisms may be associated with the risk of HCC.