title: Relationships between cell cycle pathway gene polymorphisms and risk of hepatocellular carcinoma.
abstract: OBJECTIVE
  To investigate the associiations 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 isolated from peripheral venous blood using Phenol-Chloroform. The genotyping was performed using the Sequenom MassARRAY iPLEX 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 KAT2B 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 HBsAg-positive and non-drinking and non-smoking (P < 0.05, respectively) and for those who were carriers of CHEK1 rs515255 TC, TT, TC/TT and were also HBsAg-negative and non-drinking (P < 0.05, respectively). Moreover, the risk was higher for those who were carriers of KAT2B rs17006625 GG and were also HBsAg-negative (P < 0.05).
  
  
  CONCLUSIONS
  Of 12 cell cycle pathway genes, MCM4, CHEK1 and KAT2B polymorphisms may be associated with the risk of HCC.
authors.affiliation: Yue-Li Nan, Yang Xu, Shu Li, Ting Li, Xiao-Yun Zeng, Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Yue-Li
authors.initials: YL
authors.lastname: Nan
authors.affiliation: Yue-Li Nan, Yang Xu, Shu Li, Ting Li, Xiao-Yun Zeng, Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Hu
authors.affiliation: Yue-Li Nan, Yang Xu, Shu Li, Ting Li, Xiao-Yun Zeng, Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Zhi-Ke
authors.initials: ZK
authors.lastname: Liu
authors.affiliation: Yue-Li Nan, Yang Xu, Shu Li, Ting Li, Xiao-Yun Zeng, Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Duan
authors.affiliation: Yue-Li Nan, Yang Xu, Shu Li, Ting Li, Xiao-Yun Zeng, Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Yue-Li Nan, Yang Xu, Shu Li, Ting Li, Xiao-Yun Zeng, Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.affiliation: Yue-Li Nan, Yang Xu, Shu Li, Ting Li, Xiao-Yun Zeng, Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Yue-Li Nan, Yang Xu, Shu Li, Ting Li, Xiao-Yun Zeng, Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Da-Fang
authors.initials: DF
authors.lastname: Chen
authors.affiliation: Yue-Li Nan, Yang Xu, Shu Li, Ting Li, Xiao-Yun Zeng, Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Zeng
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics; D000328:Adult; D000428:Alcohol Drinking / Q000453:epidemiology; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins; D000071877:Checkpoint Kinase 1 / Q000235:genetics; D002681:China / Q000453:epidemiology; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D019694:Hepatitis B, Chronic / Q000453:epidemiology; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D064148:Minichromosome Maintenance Complex Component 4 / Q000235:genetics; D064168:Minichromosome Maintenance Complex Component 7 / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011110:Polymorphism, Genetic; D050717:Retinoblastoma-Like Protein p130 / Q000235:genetics; D051900:Smad3 Protein / Q000235:genetics; D012907:Smoking / Q000453:epidemiology; D053782:Transforming Growth Factor beta3 / Q000235:genetics; D020687:cdc25 Phosphatases / Q000235:genetics; D050880:p300-CBP Transcription Factors / Q000235:genetics; D000099224:p300-CBP-Associated Factor
chemical_list: D048948:14-3-3 Proteins; D018797:Cell Cycle Proteins; D000071877:Checkpoint Kinase 1; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D064148:Minichromosome Maintenance Complex Component 4; D064168:Minichromosome Maintenance Complex Component 7; D009687:Nuclear Proteins; D010750:Phosphoproteins; D050717:Retinoblastoma-Like Protein p130; D051900:Smad3 Protein; D053782:Transforming Growth Factor beta3; D020687:cdc25 Phosphatases; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C493956:CDKN1A protein, human; C000614131:CDKN2A protein, human; C429022:RAD21 protein, human; C493837:RBL2 protein, human; C497790:SMAD3 protein, human; C509044:TGFB3 protein, human; C482982:YWHAB protein, human; C000605867:CHEK1 protein, human; C517009:CDC25C protein, human; C099243:MCM4 protein, human; C101624:MCM7 protein, human
keywords: Case-control study; Cell cycle pathway genes; Genetic susceptibility; Hepatocellular carcinoma; Single nucleotide polymorphism