title: Quantitative evaluation of hepatitis B virus mutations and hepatocellular carcinoma risk: a meta-analysis of prospective studies.
abstract: BACKGROUND
  The temporal relationship between hepatitis B virus (HBV) mutations and hepatocellular carcinoma (HCC) remains unclear.
  
  
  METHODS
  We conducted a meta-analysis including cohort and nested case-control studies to prospectively examine the HCC risk associated with common variants of HBV in the PreS, Enhancer II, basal core promoter (BCP) and precore regions. Pertinent studies were identified by searching PubMed, Web of Science and the Chinese Biological Medicine databases through to November 2014. Study-specific risk estimates were combined using fixed or random effects models depending on whether significant heterogeneity was detected.
  
  
  RESULTS
  Twenty prospective studies were identified, which included 8 cohort and 12 nested case-control studies. There was an increased risk of HCC associated with any PreS mutations with a pooled relative risk (RR) of 3.82 [95% confidence interval (CI): 2.59-5.61]. The pooled-RR for PreS deletion was 3.98 (95% CI: 2.28-6.95), which was higher than that of PreS2 start codon mutation (pooled-RR=2.63, 95% CI: 1.30-5.34). C1653T in Enhancer II was significantly associated with HCC risk (pooled-RR=1.83; 95% CI: 1.21-2.76). For mutations in BCP, statistically significant pooled-RRs of HCC were obtained for T1753V (pooled-RR=2.09; 95% CI: 1.49-2.94) and A1762T/G1764A double mutations (pooled-RR=3.11; 95% CI: 2.08-4.64). No statistically significant association with HCC risk was observed for G1896A in the precore region (pooled-RR=0.77; 95% CI: 0.47-1.26).
  
  
  CONCLUSIONS
  This study demonstrated that PreS mutations, C1653T, T1753V, and A1762T/G1764A, were associated with an increased risk of HCC. Clinical practices concerning the HCC risk prediction and diagnosis may wish to focus on patients with these mutations.
authors.affiliation: 1 School of Public Health, Fudan University, Shanghai 200032, China ; 2 State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200032, China ; 3 Cancer Surveillance Section, International Agency for Research on Cancer, 150 Cours Albert Thomas, F-69372 Lyon Cedex 08, France.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 1 School of Public Health, Fudan University, Shanghai 200032, China ; 2 State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200032, China ; 3 Cancer Surveillance Section, International Agency for Research on Cancer, 150 Cours Albert Thomas, F-69372 Lyon Cedex 08, France.
authors.forename: Jiang-Wei
authors.initials: JW
authors.lastname: Sun
authors.affiliation: 1 School of Public Health, Fudan University, Shanghai 200032, China ; 2 State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200032, China ; 3 Cancer Surveillance Section, International Agency for Research on Cancer, 150 Cours Albert Thomas, F-69372 Lyon Cedex 08, France.
authors.forename: Long-Gang
authors.initials: LG
authors.lastname: Zhao
authors.affiliation: 1 School of Public Health, Fudan University, Shanghai 200032, China ; 2 State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200032, China ; 3 Cancer Surveillance Section, International Agency for Research on Cancer, 150 Cours Albert Thomas, F-69372 Lyon Cedex 08, France.
authors.forename: Freddie
authors.initials: F
authors.lastname: Bray
authors.affiliation: 1 School of Public Health, Fudan University, Shanghai 200032, China ; 2 State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200032, China ; 3 Cancer Surveillance Section, International Agency for Research on Cancer, 150 Cours Albert Thomas, F-69372 Lyon Cedex 08, France.
authors.forename: Yong-Bing
authors.initials: YB
authors.lastname: Xiang
keywords: Hepatitis B virus (HBV); hepatocellular carcinoma (HCC); meta-analysis; mutation; prospective study