Hepatitis B, aflatoxin B-1, and p53 codon 249 mutation in hepatocellular carcinomas from Guangxi, People's Republic of China, and a meta-analysis of existing studies

The incidence of hepatocellular carcinomas (HCC) varies widely worldwide, w ith some of the highest incidence rates found in China. Chronic infection w ith the hepatitis B virus (HBV) and exposure to aflatoxins in foodstuffs ar e the main risk factors. A G to T transversion at codon 249 of the p53 gene (249(ser)) is commonly found in HCCs from patients in regions with dietary aflatoxin exposure. Because HBV infection is often endemic in high aflatox in exposure areas, it is still unclear whether HBV acts as a confounder or as a synergistic partner in the development of the 249(ser) p53 mutation. O ur report has two aims. First, we contribute data on HCCs from southern Gua ngxi, a high aflatoxin exposure area. Using DNA sequencing, we found that 3 6% (18 of 50) of tumors had a 249(ser) mutation. Also, 50% (30 of 60) were positive for p53 protein accumulation and 78% (28 of 36) were positive for HBV surface antigen, as detected by immunohistochemistry. Second, we presen t a metaanalysis, using our results along with those from 48 published stud ies, that examines the interrelationships among aflatoxin exposure, HBV inf ection, and p53 mutations in HCCs. We used a method that takes into account both within-study and study-to-study variability and found that the mean p roportion of HCCs with the 249(ser) mutation was positively correlated with aflatoxin exposure (P = 0.0001). We found little evidence for an HBV-aflat oxin interaction modulating the presence of the p53 249(ser) mutation or an y type of p53 mutation.