p53 mutation pattern in hepatocellular carcinoma in workers exposed to vinyl chloride

BACKGROUND. Vinyl chloride (VC) is a known animal and human carcinogen that is associated With liver angiosarcoma and most likely also with hepatocell ular carcinoma (HCC) in humans. METHODS. The authors examined the presence of p53 gene mutations in 18 HCC specimens from patients with known exposure to VC (median, 8883 parts per m illion-years; median duration, 245 months). In all cases, other risk factor s for the development of HCC (hepatitis B virus and hepatitis C virus infec tions, alcohol consumption, and metabolic or autoimmune disorders) were exc luded. Three patients had concomitant cirrhosis. The p53 gene was examined by direct sequencing of exons 5-9. RESULTS. Mutations of the p53 gene were found in 11 of 18 HCCs examined. Th e paint mutations detected were comprised of five transversions and five tr ansitions. Five of II mutations (codons 175, 245, 248, 273, and 282) occurr ed at CpG sites. Histopathologic fiver alterations (mild sinusoidal dilatat ion, [partal] fibrosis, and centrilobular siderosis) in tumor surrounding n onneoplastic liver confirmed exposure to VC. CONCLUSIONS. The results of the current study indicated a relation between VC exposure and the development of HCC. The mutation pattern of p53 with, a nearly equal rate of incidence of transitions and transversions and a high rate of incidence of mutations at CpG sites may reflect endogenous mechani sms (e.g., deamination of 5-methylcytosine) rather than exogenous carcinoge ns. (C) 2000 American Cancer Society.