title: Pre-S deletion and complex mutations of hepatitis B virus related to young age hepatocellular carcinoma in Qidong, China.
abstract: OBJECTIVE
  To investigate the roles of biomedical factors, hepatitis B virus (HBV) DNA levels, genotypes, and specific viral mutation patterns on the progression of hepatocellular carcinoma (HCC) patients below 40 years of age in Qidong, China.
  
  
  METHODS
  We conducted a case-control study within a cohort of 2387 male HBV carriers who were recruited from August, 1996. The HBV DNA sequence was determined in 49 HCC and 90 chronic hepatitis (CH) patients below 40 years of age. Mutation exchanges during follow-up in 32 cases were compared with 65 controls with paired serum samples. In addition, a consecutive series of samples from 14 HCC cases were employed to compare the sequences before and after the occurrence of HCC.
  
  
  RESULTS
  After adjustment for age, history of cigarette smoking and alcohol consumption, HBeAg positive, HBV DNA levels ≥4.00 log(10) copies/mL, pre-S deletion, T1762/A1764 double mutations, and T1766 and/or A1768 mutations were associated with risk of young age HCC. Moreover, the presence of an increasing number of HCC-related mutations (pre-S deletion, T1762/A1764, and T1766 and/or A1768 mutations) was associated with an increased risk of young age HCC. Paired samples analysis indicated that the increased HCC risk for at-risk sequence mutations were attributable to the persistence of these mutations, but not a single time point mutation. The longitudinal observation demonstrated a gradual combination of pre-S deletion, T1762/A1764 double mutations, and T1766 and/or A1768 mutations during the development of HCC.
  
  
  CONCLUSIONS
  High HBV DNA levels and pre-S deletion were independent risk factors of young age HCC. Combination of pre-S deletion and core promoter mutations increased the risk and persistence of at-risk sequence mutations is critical for HCC development.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Jiangsu Province, China.
authors.forename: Lishuai
authors.initials: L
authors.lastname: Qu
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Kuai
authors.forename: Taotao
authors.initials: T
authors.lastname: Liu
authors.forename: Taoyang
authors.initials: T
authors.lastname: Chen
authors.forename: Zhengpin
authors.initials: Z
authors.lastname: Ni
authors.forename: Xizhong
authors.initials: X
authors.lastname: Shen
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000453:epidemiology* / Q000821:virology*; D016022:Case-Control Studies; D002681:China; D004279:DNA, Viral / Q000097:blood; D018450:Disease Progression; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens
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