1. Predictive power of hepatitis B 1762T/1764A mutations in plasma for hepatocellular carcinoma risk in Qidong, China.
- Author
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Muñoz, Alvaro, Chen, Jian Guo, Egner, Patricia A., Marshall, Melinda L., Johnson, Jamie L., Schneider, Michael F., Lu, Jian Hua, Zhu, Yuan Rong, Wang, Jin-Bing, Chen, Tao Yang, Kensler, Thomas W., and Groopman, John D.
- Subjects
HEPATITIS B ,GENETIC mutation ,BLOOD plasma ,CANCER risk factors ,LIVER cancer ,CANCER-related mortality ,HEPATITIS B virus - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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