title: Phosphatase and tensin homologue genetic polymorphisms and their interactions with viral mutations on the risk of hepatocellular carcinoma.
abstract: BACKGROUND
  Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). Some HBV mutants and dysregulation of phosphatase and tensin homolog (PTEN) may promote the development of HCC synergistically. We aimed to test the effects of PTEN genetic polymorphisms and their interactions with important HBV mutations on the development of HCC in HBV-infected subjects.
  
  
  METHODS
  Quantitative polymerase chain reaction was applied to genotype PTEN polymorphisms (rs1234220, rs2299939, rs1234213) in 1012 healthy controls, 302 natural clearance subjects, and 2011 chronic HBV-infected subjects including 1021 HCC patients. HBV mutations were determined by sequencing. The associations of PTEN polymorphisms and their interactions with HBV mutations with HCC risk were assessed using multivariate logistic regression analysis.
  
  
  RESULTS
  Rs1234220 C allele was significantly associated with HCC risk compared to healthy controls (adjusted odds ratio [AOR] = 1.35, 95% confidence interval [CI] = 1.07-1.69) and HCC-free HBV-infected subjects (AOR = 1.27, 95% CI = 1.01-1.57). rs1234220 C allele was significantly associated with increased frequencies of HCC-risk A1652G, C1673T, and C1730G mutations in genotype B HBV-infected subjects. Rs2299939 GT genotype was inversely associated with HCC risk in HBV-infected patients (AOR = 0.75, 95% CI = 0.62-0.92). The interaction of rs2299939 variant genotypes (GT+TT) with A3054T mutation significantly increased HCC risk (AOR = 2.41, 95% CI = 1.08-5.35); whereas its interaction with C3116T mutation significantly reduced HCC risk (AOR = 0.34, 95% CI = 0.18-0.66). These significant effects were only evident in males after stratification.
  
  
  CONCLUSIONS
  PTEN polymorphisms and their interactions with HBV mutations may contribute to hepatocarcinogenesis in males. The host-virus interactions are important in identifying HBV-infected subjects who are more likely to develop HCC.
authors.forename: Yan
authors.initials: Y
authors.lastname: Du
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Pu
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Hu
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Zhang
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Guang-Wen
authors.initials: GW
authors.lastname: Cao
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D000070876:Tensins
chemical_list: D008840:Microfilament Proteins; D000070876:Tensins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase