249ser p53 mutation in the serum of black southern African patients with hepatocellular carcinoma.
OBJECTIVE
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.
Kimbi
Gerald C
GC
MRC/University Molecular Hepatology Research Unit, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
Kew
Michael C
MC
Yu
Mimi C
MC
Arakawa
Kazuko
K
Hodkinson
John
J
D000293:Adolescent; D000328:Adult; D016604:Aflatoxin B1; D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood; D004032:Diet; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D044382:Population Groups; D015995:Prevalence; D012694:Serine / Q000737:chemistry; D012737:Sex Factors; D013019:South Africa / Q000453:epidemiology; D016159:Tumor Suppressor Protein p53 / Q000097:blood / Q000737:chemistry / Q000235:genetics*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D012694:Serine; D016604:Aflatoxin B1