title: Cholangiocarcinoma: risk factors, environmental influences and oncogenesis.
abstract: Cholangiocarcinoma (CCA) is one of the most frequent malignant epithelial liver tumors after hepatocellular carcinoma (HCC). Its incidence seems to be increasing worldwide, although risk factors are heterogeneous and differ globally. Although diagnostic and therapeutic medicine have advanced in several countries, tackling this tumor remains a challenge. The causes of CCA's increasing incidence are likely a differential increment of some factors according to the geographical area, which will be considered in this review. Environment-linked risk factors may play a critical role in the carcinogenesis. Liver flukes may play a major role in East Asia, while exposure to chemical compounds, such as naphthenic acids, has been postulated as a source of the rate increase in Western countries. Carcinogenesis is variable and confounding factors also need to be taken into account. Carcinogenesis depends on a sequential process and most probably involves both cholestasis and chronic inflammation as promoting steps after induction. The release and interaction of interleukin-6 (IL-6), transforming growth factor beta (TGF-beta), tumor necrosis factor alpha (TNF-alpha), and platelet-derived growth factor (PDGF) are at the basis of the proliferation of biliary epithelial cells or cholangiocytes. Additional steps for the final development of CCA may also involve an increase of the mutation rate of tumor suppressor genes, such as TP53, and the evasion of apoptosis.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Redha
authors.initials: R
authors.lastname: Al-Bahrani
authors.forename: Yasser
authors.initials: Y
authors.lastname: Abuetabh
authors.forename: Nikolas
authors.initials: N
authors.lastname: Zeitouni
authors.forename: Consolato
authors.initials: C
authors.lastname: Sergi
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D001659:Biliary Tract / Q000254:growth & development / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D002769:Cholelithiasis / Q000453:epidemiology; D005210:Fasciola hepatica / Q000472:pathogenicity; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D015994:Incidence; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000469:parasitology / Q000473:pathology*; D010578:Petroleum / Q000633:toxicity; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D010578:Petroleum; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha