In patients infected with hepatitis B virus (HBV), HBV genotype C and certain variants in the precore and basal core promotor (BCP) regions of the viral DNA are associated with an increased risk of hepatocellular carcinoma, according to a report in the Journal of the National Cancer Institute for August 20.
In prior studies, researchers have identified eight genotypes of HBV and numerous variants in the precore and BCP regions. Whether these genetic factors influence the risk of hepatocellular cancer, however, was unclear. The new findings, which are based on a study of 2762 HBV-infected subject in Taiwan, suggest that they do.
When initial blood samples were taken in 1991 and 1992, none of the patients had liver cancer, report Dr. Chien-Jen Chen, from Academia Sinica in Taipei, Taiwan, and colleagues. During 33,847 person-years of follow-up, 153 subjects were diagnosed with the malignancy.
Relative to infection with genotype B HBV, infection with genotype C increased the odds of hepatocellular carcinoma by 76 per cent. Similarly, the A1762T/G1764A double mutation in BCP raised the risk of cancer by 73 per cent.
Not all of the mutants, however, had an adverse effect. The precore G1896A variant cut the risk of hepatocellular cancer by 66 per cent, the report indicates.
"These genetic features of HBV, in addition to age, sex, HBV viral load, and serum ALT levels, may help identify those who are at increased risk for liver disease progression and would therefore potentially benefit from early interventions, such as regular screening to detect disease progression, and treatment," the authors conclude.
"Several mechanisms have been proposed to explain the higher incidence of hepatocellular carcinoma in patients infected with genotype C HBV vs. genotype B HBV," note editorialists Dr. Josep M. Llovet, from Mount Sinai School of Medicine in New York, and Dr. Anna Lok, from the University of Michigan Medical Center in Ann Arbor.
"It is possible that variations in viral sequence may contribute to this difference: several studies have found that subgenotype C2 is associated with a higher incidence of hepatocellular carcinoma than other subgenotypes of HBV genotype C," they add.
J Natl Cancer Inst 2008;100:1134-1143
