Hepatobiliary
neoplasms comprise a significant portion of the worldwide
cancer burden. Advances in basic science research have led to rapid progress in our understanding of the molecular events responsible for these dreaded diseases. The genetic changes associated with
hepatocellular carcinoma (HCC) have received the most attention.
Aflatoxin B1 exposure leads to mutations in the p53 tumor suppressor gene, most commonly a transversion in
codon 249 that leads to a substitution of
serine for
arginine in the p53
protein. Numerous other tumor suppressor genes, oncogenes, and
tumor gene pathways are altered in HCC. Hepatitis B virus (HBV)
infection is strongly associated with HCC. HBV may cause HCC either directly via the
HBV X protein, or indirectly by causing liver
inflammation and
cirrhosis. Hepatitis C virus (HCV)
infection is also associated with HCC. Recent evidence suggests that the HCV core
protein may play a role in hepatocarcinogenesis. Several inherited
metabolic diseases are associated with HCC. It is likely that these diseases cause HCC indirectly by causing
cirrhosis. The molecular pathogenesis of
cholangiocarcinoma and
gallbladder cancer has not been well defined. However, multiple tumor suppressor genes and oncogenes, including p53 and K-ras, are altered in these
tumors. Further molecular characterization of hepatobiliary
tumors may lead to earlier diagnosis, better staging, improved treatment planning, and the development of more effective
therapies.