Hepatolithiasis and intrahepatic cholangiocarcinoma: carcinogenesis based on molecular mechanisms

Hepatolithiasis is more frequently seen in East Asian countries than in Western countries, and it is well known to represent a high-risk state for intrahepatic cholangiocarcinoma. Intrahepatic cholangiocarcinoma is an aggressive tumor that shows a dismal outcome even after resection. Cancer results from multistep carcinogenesis; however, the precise molecular mechanisms involved in the genetic alterations in cancer remain unknown. The accumulation of alterations in cancer-related genes leads to disruptions in cell-cycle regulation and also to continuous cell proliferation. The present review provides an overview of cancer-related genes in intrahepatic cholangiocarcinogenesis arising in hepatolithiasis. Further study of molecular mechanisms in hepatolithiasis-related intrahepatic cholangiocarcinoma, and the delineation of the influence of the genes involved should lead to our understanding of cholangiocarcinogenesis.