HUMAN LIVER CARCINOGENESIS

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Hepatitis B and C Viruses Cooperate as Factors of Hepatocellular Carcinoma (HCC). We continue to conduct molecular epidemiology studies in the high HCC risk geographic area in Qidong, China. With our longstanding coworker Zong-tang Sun, the hypothesis that HBV and HCV have additive effects in hepatocellular carcinogenesis is being tested. We have recently analyzed data from our case-control study involving 112 histologically proven HCC cases, and 225 age- and gender-matched controls. The results are consistent with our hypothesis. Remarkably, the age-adjusted annual HCC mortality rate for Qidong residents with chronic HBV and HCV carriers is estimated to be 7%. Hepatitis B Virus and DNA Repair. We and others have previously reported that p53 can modulate nucleotide excision repair. Using a host reactivation assay, our preliminary data indicate that HBx inhibits reactivation, i.e., repair of the ultraviolet light (UV-C, 254 nm) damage plasmid. This leads to the hypothesis that HBx inhibits p53 binding to XPB or XPD DNA helicases in the basal transcription-nucleotide excision repair complex, TFIIH. We have previously demonstrated that HBx protein inhibits in vitro p53 binding to XPB. Whereas, HBx did not bind to XPB, HBx does bind to the carboxyl terminus of p53 which also is the site of XPB binding. We are currently investigating the hypothesis that HBx binds to other members of the TFIIH multiprotein complex.