MDM2 and hepatocellular carcinoma: The p53 pathway is affected at multiple levels in human HCC as follows: i) p53 mutations occur in aflatoxin-induced HCC (50%) and with lower frequency (20%–30%) in HCC not associated with aflatoxin; ii) microdeletions of p14ARF occur in 15%–20% of human HCC but rarely in p53 mutant HCC; iii) increased Mdm2 expression has been observed in human HCC; iv) the vast majority of human HCC overexpresses gankyrin, which inhibits both the pRb and p53-checkpoint functions [39].