The p53 mutation spectrum in hepatocellular carcinoma from Guangxi, China : role of chronic hepatitis B virus infection and aflatoxin B1 exposure

BACKGROUND & AIMS: p53 is one of the most frequently mutated human tumour suppressor genes. Chronic infection with hepatitis B virus (HBV) and exposure to aflatoxin B1 (AFB1) induces p53 mutations in hepatocellular carcinoma (HCC) tissue. The aims of present study are to investigate the p53 mutation spectrum in HBV- and AFB1-related hepatocarcinogenesis in patients with hepatocellular carcinoma (HCC) in Guangxi, China. METHODS: Tumour and adjacent liver tissue were collected from 397 HCC patients who were subdivided into HBV(+)/AFB1(+), HBV(+)/AFB1(-), HBV(-)/AFB1(+) and HBV(-)/AFB1(-) four groups. All 11 exons of the p53 gene were PCR-amplified and sequenced. Immunohistochemistry was used to evaluate the effect of mutations on the expression of p53 protein. RESULTS AND CONCLUSIONS: P53 mutations were detected in 223 HCC samples, 13 adjacent liver tissue samples and only 1 of 68 normal liver tissue samples. The mutation sites concentrated at exon 4, 5, 6, 7, 8, 9 and no mutation was detected in exon 1, 2, 3, 10 and 11. The most frequently occurring mutation was in codon 249 (R249S) in exon 7. Patients in the HBV(+)/AFB1(+) and HBV(-)/AFB1(+) groups had significantly higher mutation rates compared with patients in the HBV(+)/AFB1(-) and HBV(-)/AFB1(-) groups. P53 mutation status and HBV/AFB1 status were independent predictors of tumour recurrence after surgery. Immunohistochemical analysis revealed that p53 gene mutations were correlated with the p53 expression. In Guangxi area, the significant association between AFB1-induced p53 mutations and the expression of p53 protein suggest an important role for p53 mutations in carcinogenesis of HCC.