Prevalence of Aflatoxin Induced p53 Mutation at Codon 249 (R249s) in Hepatocellular Carcinoma Patients with and without Hepatitis B Surface Antigen (HBsAg)

Abstract

<b>Background:</b> A missense mutation in exon 7 (R249S) of the p53 tumor suppressor gene is characteristicof aflatoxin B1 (AFB1) exposure. AFB1 is believed to have a synergistic effect on hepatitis virus B (HBV)carcinogenesis. However, results of studies comparing R249S prevalence among patients are conflicting. The aimof this study was to determine the prevalence of the R249S mutation in hepatocellular carcinoma (HCC) patientswith or without positive HBsAg. Materials and <br/><b>Methods</b>: Paraffin embedded liver tissues were obtained from124 HCC patients who underwent liver resection and liver biopsy in King Chulalongkorn Memorial Hospital.Restriction fragment length polymorphism (RFLP) was utilized to detect the R249S mutation. Positive resultswere confirmed by direct sequencing. <br/><b>Results</b>: Sixty four (52%) patients were positive for HBsAg and 18 (15%)were anti-HCV positive. 12 specimens tested positive by RFLP. Ten HCC patients (8.1%) were confirmed to beR249S positive by Sanger sequencing (AGG to AGT). Out of these 10, six were HBsAg positive, and out of theremaining 4, two were anti-HCV positive. The R249S prevalence among HCC patients with positive HBsAg was9.4% compared to 6.7% for HBsAg negative samples. Patients with the R249S mutation were younger (55±10vs 60±13 year-old) and tended to have a more advanced Edmonson-Steiner grade of HCC, although differencesdid not reach statistical significance. <br/><b>Conclusions</b>: Our study shows moderate prevalence of aflatoxin B1-relatedp53 mutation (R249S) in HCC with or without HBsAg. HBsAg positive status was not associated with R249Sprevalence.