A joint effect between the MDM2 and TP53 polymorphisms and an increased risk of liver cancer was detected, with the odds ratio for the presence of both MDM2 309GG and TP53 72Pro/Pro genotypes being 10 (95% confidence interval 0.39-255.55).
This study has identified some important novel ways in which WtHBx and MutHBx differentially interact with p53 and this could begin to form the cellular explanation for the association between this particular mutant and liver cancer.
The mutation Arg114Gly was predicted bioinformatically to affect Nogo-66 dimensional structure of Nogo-C. Our previous works also had indicated that mutant Nogo-C promoted liver cancer cell line apoptosis and resulted in molecular marker of HCC p53 gene transfer from nucleus to cytoplast.
This study confirms that beta-catenin deregulation is involved in sporadic hepatoblastoma and also suggests that mismatch repair defects and p53 mutations contribute to this rare liver cancer.
However, wild-type mice in which AFB1 alone was used to induce liver cancers have failed to recapitulate p53 mutations, raising the possibility that mouse DNA context may not be appropriate for the generation of AFB1-induced p53 mutations.
Our results indicate that, in liver cancer, the cytotoxic somatostatin analogue AN-238 is a powerful agent that can induce apoptosis, through sst(s) and independently of p53.
Hepatitis B virus and possibly hepatitis C virus, but not alcohol, should be responsible, to a degree, for the mutational change in p53 protein in hepatocellular cancer patients with chronic liver disease.
Aflatoxin may increase the proportion of p53 mutations by causing a single mutation, the codon 249 G > T transversion, thus explaining some of the excess liver cancer associated with aflatoxin exposure.
Mutations in p53 have successfully been used to establish links between dietary aflatoxin exposure and liver cancer, exposure to ultraviolet light and skin cancer, smoking and cancers of the lung and bladder, and vinyl chloride exposure and liver cancer.
In support of this interpretation, we found no mutations in exons 5-8 of the p53 gene in 13 iatrogenic liver cancers induced by injection of Thorotrast, an alpha-emitting radiocontrast agent.
Tumor suppressor genes such as p53 contribute to the oncogenic process via loss-of-function mechanisms such as genetic mutation or complex formation with other cellular or viral proteins. p53 is mutated in approximately 50% of human tumors and has an important role in the genesis or progression of both colorectal and hepatocellular cancers.
Thus, detection of the codon 249 mutant p53 mRNA by differential in situ hybridization is a specific method for studying the mutation-specific expression of the p53 gene in liver cancers at the cellular level, while simultaneously visualizing the cell morphology.
These results indicate that p53 is overexpressed in a majority of childhood liver cancers, but this abnormal p53 expression does not seem to be caused by mutations in the p53 gene.
As Senegal is a country where liver cancer incidence is one of the highest in the world and where people are highly exposed to aflatoxin, we screened 15 liver cancer samples from this country for mutation at codon 249 of the p53 gene.
Considering the possibility that MYC may amplify the expression of PPARA target genes to potentiate cell proliferation and liver cancer, gene expression was analyzed from livers of wild-type and liver-specific Myc knockout (Myc<sup>ΔHep</sup> ) mice treated with the PPARA agonist pirinixic acid.
The p16 protein expressions in liver cancer and para-carcinoma tissues were detected via immunohistochemistry (IHC), and the correlations of p16 positive expression with ultrasound parameters were also analyzed.