Geographic Variation of p53 Mutational Profile in Nonmalignant Human Liver

Fifty-eight percent of hepatocellular carcinomas (HCCs) from Qidong, China, contain an AGG to AGT mutation at codon 249 of the p53 tumor suppressor gene, a mutation that is rarely seen in HCCs from Western countries. The population of Qidong is exposed to high levels of aflatoxin B_1 (AFB_1), a fungal toxin that has been shown to induce the same mutation in cultured human HCC cells. To investigate the role of AFB_1 and of these p53 mutations in hepatocarcinogenesis, normal liver samples from the United States, Thailand, and Qidong (where AFB_1 exposures are negligible, low, and high, respectively) were examined for p53 mutations. The frequency of the AGG to AGT mutation at codon 249 paralleled the level of AFB_1 exposure, which supports the hypothesis that this toxin has a causative-and probably early-role in hepatocarcinogenesis.