title: Predictive power of hepatitis B 1762T/1764A mutations in plasma for hepatocellular carcinoma risk in Qidong, China.
abstract: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality with nearly 700,000 deaths occurring annually. Hepatitis B virus (HBV) is a major contributor to HCC and acquired mutations in the HBV genome may accelerate its pathogenesis. In this study, a matched case-control investigation of 345 men who died of HCC and 625 controls were nested within a cohort of male hepatitis B surface antigen (HBsAg) carriers from Qidong, China. Matched preserving odds ratios (ORs) were used as a measure of association and 95% confidence intervals (CIs) as a measure of precision. Real-time polymerase chain reaction allowed for a quantitative comparison of the levels of the HBV 1762(T)/1764(A) mutation in cases and controls. A total of 278 (81%) of the cases were positive for the HBV 1762(T)/1764(A) mutation compared with 250 (40%) of the controls. The matched preserving OR of 6.72 (95% CI: 4.66 to 9.68) strongly indicated that cases were significantly more probably than controls to have the mutation. Plasma levels of DNA harboring the HBV mutation were on average 15-fold higher in cases compared with controls (P < 0.001). Most strikingly, the level of the mutation in the 20 controls who later developed and died of HCC were on average 274-fold higher than controls who did not develop HCC. Thus, within this cohort of HBsAg carriers at high risk of developing HCC, individuals positive for the HBV 1762(T)/1764(A) mutation at enrollment were substantially more probably to subsequently develop HCC, with a higher concentration of the mutation in plasma enhancing predisposition for cancer development.
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Muñoz
authors.forename: Jian Guo
authors.initials: JG
authors.lastname: Chen
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Egner
authors.forename: Melinda L
authors.initials: ML
authors.lastname: Marshall
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Michael F
authors.initials: MF
authors.lastname: Schneider
authors.forename: Jian Hua
authors.initials: JH
authors.lastname: Lu
authors.forename: Yuan Rong
authors.initials: YR
authors.lastname: Zhu
authors.forename: Jin-Bing
authors.initials: JB
authors.lastname: Wang
authors.forename: Tao Yang
authors.initials: TY
authors.lastname: Chen
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Kensler
authors.forename: John D
authors.initials: JD
authors.lastname: Groopman
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000209:etiology*; D016022:Case-Control Studies; D002681:China; D015331:Cohort Studies; D004279:DNA, Viral / Q000235:genetics*; D006509:Hepatitis B / Q000097:blood / Q000150:complications / Q000235:genetics*; D006514:Hepatitis B Surface Antigens; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016017:Odds Ratio; D011379:Prognosis; D012307:Risk Factors
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens