title: Association of a potential functional pre-miR-218 polymorphism and its interaction with hepatitis B virus mutations with hepatocellular carcinoma risk.
abstract: OBJECTIVE
  MicroRNA-218 (miR-218) can function as a tumour suppressor and inactivate cancer-promoting inflammation. However, role of miR-218 on hepatocellular carcinoma (HCC) remains unclear. To determine the contribution of miR-218 genetic predisposition and its interaction with hepatitis B virus (HBV) mutations to HCC risk.
  
  
  METHODS
  rs11134527 located at putative promoter region of pre-miR-218 was genotyped in 1012 healthy controls, 302 hepatitis B surface antigen (HBsAg) seroclearance subjects and 2011 subjects with chronic HBV infection (1021 with HCC) using quantitative PCR. HBV mutation was determined by sequencing.
  
  
  RESULTS
  rs11134527 variant genotypes in dominant model was associated with HCC risk compared with all HCC-free subjects [odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.04-1.43], HCC-free HBsAg-positive subjects (OR = 1.23, 95% CI = 1.02-1.50) and HBsAg seroclearance subjects (OR = 1.45, 95% CI = 1.08-1.96), adjusting for age and gender, and also associated with the generation of HBV preS deletion in men (adjusted OR = 1.85, 95% CI = 1.23-2.76). In multivariate regression analyses, rs11134527 in dominant model was associated with HCC risk (OR = 1.50, 95% CI = 1.05-2.13), whereas its multiplicative interaction with viral mutation T1674C/G was inversely associated with HCC risk (OR = 0.44, 95% CI = 0.21-0.96), adjusting for covariates including HBV mutations in the enhancer II-precore region; its interaction with HBV preS1 start codon mutation was associated with HCC risk (OR = 4.44, 95% CI = 1.27-15.55), adjusting for covariates including HBV mutations in the preS region.
  
  
  CONCLUSIONS
  rs11134527 may be a novel genetic risk factor of HCC in HBV-exposed subjects, can facilitate HBV preS deletion generation and predispose the host to the effect of T1674C/G and preS1 start codon mutation in hepatocarcinogenesis.
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Yifang
authors.initials: Y
authors.lastname: Han
authors.forename: Rui
authors.initials: R
authors.lastname: Pu
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Weiping
authors.initials: W
authors.lastname: Li
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yin
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Shen
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Xie
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Shuang
authors.initials: S
authors.lastname: Jiang
authors.forename: Juhong
authors.initials: J
authors.lastname: Li
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
authors.forename: Guangwen
authors.initials: G
authors.lastname: Cao
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D005814:Genes, Viral; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D014779:Virus Replication
chemical_list: C547471:MIRN218 microRNA, human; D035683:MicroRNAs
keywords: hepatitis B virus; hepatocellular carcinoma; miR-218; mutation; polymorphysims