Predictive power of hepatitis B 1762T/1764A mutations in plasma for hepatocellular carcinoma risk in Qidong, China

Alvaro Muñozy, Jian Guo Chen, Patricia A. Egner, Melinda L. Marshall, Jamie L. Johnson, Michael F. Schneider, Jian Hua Lu, Yuan Rong Zhu, Jin Bing Wang, Tao Yang Chen, Thomas W. Kensler, John D. Groopman

Research output: Contribution to journalArticlepeer-review

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 1762T/1764A mutation in cases and controls. A total of 278 (81%) of the cases were positive for the HBV 1762T/1764A 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 1762T/1764A 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.

Original languageEnglish (US)
Pages (from-to)860-865
Number of pages6
JournalCarcinogenesis
Volume32
Issue number6
DOIs
StatePublished - Jun 1 2011

ASJC Scopus subject areas

  • Cancer Research

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