Hepatitis B 1762T/1764A mutations, hepatitis C infection, and codon 249 p53 mutations in hepatocellular carcinomas...

Hepatocellular carcinoma is one of the leading causes of cancer death worldwide. The etiology of liver cancer is multifactorial, and infection with hepatitis B virus (HBV), whose pathogenesis is exacerbated by the acquisition of mutations that accelerate carcinogenesis, or hepatitis C virus (HCV) and dietary exposure to aflatoxin B(1) all contribute to elevating one's risk for this disease. In this study, we sought to determine the contributions of these agents by measuring the occurrence of an HBV 1762(T)/1764(A) double mutation, an aflatoxin-specific 249(G-->T) mutation of the p53 gene, and HCV in plasma of 34 HCC cases and 68 age- and gender-matched controls, and in 25 liver tumors from northern Thailand. In total, 14 cases, 5 controls, and 19 tumors had detectable levels of HBV DNA. All 14 cases, 2 controls (2.9%), and 17 tumors (89.5%) were positive for the HBV double mutation. Nine cases (26.5%), 10 controls (14.7%), and 6 tumors (24%) were positive for the p53 mutation. Five cases (14.7%), no controls, and 4 tumors (16%) had both mutations. The median age of HCC diagnosis in these 5 cases was 34 years versus 51 years for other cases. Five cases (14.7%) and 1 control (1.5%) were HCV enzyme immunoassay positive. Thus, specific HBV, HCV, and aflatoxin biomarkers reveal the complexity of risks contributing to HCC in northern Thailand and suggest further application of these biomarkers as intermediate end points in prevention, intervention trials, and etiologic investigations.