p53 mutations and aflatoxin B1 exposure in hepatocellular carcinoma patients from Thailand.
The prevalence and type of mutations in the p53 tumour-suppressor gene have been determined in 15 hepatocellular carcinomas (HCC) originating from Thailand. Direct sequencing of exons 5-8 revealed 2 mutations, an AGG to AGT (Arg-->Ser) transversion at codon 249, and an ATC-->AAC (Ile-->Asn) transversion at codon 254. Samples from the Thai patients were analyzed for the presence of aflatoxin-liver DNA and aflatoxin-serum albumin adducts, and all but one were found negative. All the patients were genotyped for glutathione-S-transferase (GST) mu, an enzyme possibly involved in the detoxification of AFB1, and 12 out of 15 had the null genotype. In general, the level of aflatoxin-albumin adducts in sera and the prevalence of p53 mutation at codon 249 in HCC were lower than in other areas at high risk of HCC, including southern China and parts of Africa.
Unit of Mechanisms of Carcinogenesis, International Agency for Research on Cancer, Lyon, France.
M C
MC
Hollstein
C P
CP
Wild
F
F
Bleicher
S
S
Chutimataewin
C C
CC
Harris
P
P
Srivatanakul
R
R
Montesano
D000293:Adolescent; D000328:Adult; D016604:Aflatoxin B1 / Q000032:analysis* / Q000378:metabolism; D000368:Aged; D000595:Amino Acid Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis* / Q000378:metabolism; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D015995:Prevalence
D004273:DNA, Neoplasm; D016604:Aflatoxin B1; D005982:Glutathione Transferase