249serp53 mutation in the serum of black southern African patients with hepatocellular carcinoma

Abstract Background and Aims: A specific mutation at codon 249 of the p53 tumor suppressor gene (guanine to thymine; arginine to serine [249 serine p53 ]) is present in the cell‐free plasma of 30–47% of patients with hepatocellular carcinoma (HCC) in regions with uniformly high levels of dietary exposure to the fungal toxin, aflatoxin B 1 . No information is available from other regions. We therefore examined cell‐free serum from HCC patients in southern Africa, where aflatoxin B 1 exposure ranges from very high to low levels. Methods: DNA extracted from the serum of 158 black African patients with HCC was amplified by the polymerase chain reaction assay using primers specific for exon 7 of the p53 gene, and submitted to endonuclease cleavage with HaeIII to identify the 249 serine p53 mutation. The presence of the mutation was confirmed by nucleotide sequencing. Results: The specific mutation was detected in 18% of the patients, giving an odds ratio for HCC in those with the mutation of 13.3 (95% confidence limits 1.8; 100.2). Surprisingly, the mutation was present equally often in rural and urban patients, despite presumed levels of aflatoxin B 1 exposure in the latter being much lower. No correlation was found with the presence of hepatitis B virus infection or the age, sex or tribe of the patients. Conclusions: The 249 serine p53 mutation is found less often in the serum of patients with HCC in a region with variable levels of exposure to aflatoxin B 1 than in those with uniformly high levels of exposure, but the mutation does occur in black Africans with presumed lower levels of exposure to the fungal toxin.