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: Alvaro Muñoz, 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
• Journal: Carcinogenesis (Carcinogenesis) Vol. 32 Issue 6 Pg. 860-5 (Jun 2011) ISSN: 1460-2180 [Electronic] England
• PMID: 21474708 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• DNA, Viral
• Hepatitis B Surface Antigens

Topics

• Adult
• Carcinoma, Hepatocellular (blood, etiology)
• Case-Control Studies
• China
• Cohort Studies
• DNA, Viral (genetics)
• Hepatitis B (blood, complications, genetics)
• Hepatitis B Surface Antigens
• Hepatitis B virus (genetics)
• Humans
• Liver Neoplasms (blood, etiology)
• Male
• Middle Aged
• Mutation (genetics)
• Odds Ratio
• Prognosis
• Risk Factors