title: Interaction of signal transducer and activator of transcription 3 polymorphisms with hepatitis B virus mutations in hepatocellular carcinoma.
abstract: Hepatitis B virus (HBV) mutations and signal transducer and activator of transcription 3 (STAT3) activation are closely associated with hepatocellular carcinoma (HCC). However, single nucleotide polymorphisms (SNPs) of STAT3 have not been implicated in HCC susceptibility. This study was designed to evaluate the effect of STAT3 SNPs and their interactions with HBV mutations on HCC risk. A total of 2,011 HBV-infected subjects (including 1,021 HCC patients) and 1,012 healthy controls were involved in this study. SNPs rs4796793 (-1697, C>G), rs2293152 (intron 11, C>G), and rs1053004 (3' untranslated region, T>C) were genotyped using quantitative polymerase chain reaction. HBV mutations were determined via direct sequencing. It was found that rs2293152 (GG versus CC) was significantly associated with HCC risk compared with the subjects without HCC, adjusting for age and sex (adjusted odds ratio [AOR], 1.30; 95% confidence interval [CI], 1.04-1.62). The impact of rs2293152 was greater in women compared with men. Compared with HCC-free HBV-infected subjects, rs2293152 GG was solely associated with HCC in women (AOR, 2.04; 95% CI, 1.15-3.61). rs2293152 GG was significantly associated with high viral load (≥1 × 10(4) copies/mL) (AOR, 1.37; 95%, CI 1.01-1.88) and increased frequencies of T1674C/G (AOR, 1.61; 95% CI, 1.06-2.46) and A1762T/G1764A (AOR, 1.64; 95% CI, 1.14-2.35). In multivariate regression analyses, multiplicative interaction of rs1053004 with T1674C/G significantly increased HCC risk, whereas rs2293152 and A1726C interaction reduced it, adjusting for covariates including HBV mutations in the enhancer II/basal core promoter/precore region; the interaction of rs4796793 with preS2 start codon mutation significantly increased HCC risk, adjusting for covariates including HBV mutations in the preS region.
  
  
  CONCLUSIONS
  STAT3 SNPs appear to predispose the host with HBV mutations to hepatocarcinogenesis, and this effect may differ in men versus women. STAT3 SNPs may have applicability in future HCC surveillance algorithms. (Hepatology 2013;57:2369-2377).
authors: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors: Jiaxin
authors: J
authors: Xie
authors: Yuwei
authors: Y
authors: Zhang
authors: Qi
authors: Q
authors: Zhang
authors: Yifang
authors: Y
authors: Han
authors: Jianhua
authors: J
authors: Yin
authors: Rui
authors: R
authors: Pu
authors: Qiuxia
authors: Q
authors: Shen
authors: Wei
authors: W
authors: Lu
authors: Yan
authors: Y
authors: Du
authors: Jun
authors: J
authors: Zhao
authors: Xue
authors: X
authors: Han
authors: Hongwei
authors: H
authors: Zhang
authors: Guangwen
authors: G
authors: Cao
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000276:immunology / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D050796:STAT3 Transcription Factor / Q000235:genetics*; D012737:Sex Factors; D014779:Virus Replication / Q000235:genetics
chemical_list: D006513:Hepatitis B e Antigens; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human