p53 mutations in British patients with hepatocellular carcinoma: Clustering in genetic hemochromatosis

Background & Aims: Environmental factors are important in the etiology of h epatocellular carcinoma (HCC). Aflatoxin B1 causes a specific point mutatio n in the p53 tumor-suppressor gene in exposed individuals, in Western popul ations, mutations of this gene seem to be less frequent. We have investigat ed the role of p53 mutations in tumorigenesis in British patients with HCC. The aim of this study was to determine the frequency and mutational spectr um of the p53 gene in HCCs from British patients. Methods: DNA from 170 HCC s, of well-defined etiology, in British patients was analyzed by single-str anded conformational polymorphism using the polymerase chain reaction techn ique. Mutations were then characterized by direct sequencing. Results: Twen ty-nine percent of tumors had p53 mutations. Ten of 14 (71%) hemochromatoti c cancers had mutations within the p53 gene, and clustering of these mutati ons at codon 220 (A-G) was found in 5 cases; 3 others had T-A mutations. No clustering was found in HCCs with other etiologies. Conclusions: p53 mutat ions are more common than was thought in Northern European HCCs. This is th e first demonstration of p53 mutational clustering in HCCs from hemochromat otic subjects.