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249 ser p53 mutation in the serum of black southern African patients with hepatocellular carcinoma
Author(s) -
KIMBI GERALD C,
KEW MICHAEL C,
YU MIMI C,
ARAKAWA KAZUKO,
HODKINSON JOHN
Publication year - 2005
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2005.03951.x
Subject(s) - hepatocellular carcinoma , medicine , mutation , microbiology and biotechnology , hepatitis b virus , serine , polymerase chain reaction , gene , biology , cancer research , virology , genetics , virus , phosphorylation
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.