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comprehension of the carcinogenic pathways determining neoplastic changes, which all limit the pursuit of appropriate treatment. Several risk factors have been recognized, including different infective, immune-mediated, and dysmorphogenic disorders of the biliary tree. In this review, we report the details of possible mechanisms that lead a specific premalignant pathological condition to become cholangiocarcinoma. For instance, during liver fluke infection, factors secreted from the worms may play a major role in pathogenesis. In primary sclerosing cholangitis, deregulation of histamine and bile-acid signaling may determine important changes in cellular pathways. The study of these molecular events may also shed some light on the pathogenesis of sporadic (unrelated to risk factors) forms of cholangiocarcinoma, which represent the majority (nearly 75%) of cases.<\/jats:p>","DOI":"10.3390\/cancers14061442","type":"journal-article","created":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T01:40:23Z","timestamp":1646962823000},"page":"1442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Molecular Mechanisms Linking Risk Factors to Cholangiocarcinoma Development"],"prefix":"10.3390","volume":"14","author":[{"given":"Ludovica","family":"Ceci","sequence":"first","affiliation":[{"name":"Hepatology and Gastroenterology Division, Department of Medicine, Indiana University, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hepatology and Gastroenterology Division, Department of Medicine, Indiana University, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Lenci","sequence":"additional","affiliation":[{"name":"Unit of Hepatology, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8983-4305","authenticated-orcid":false,"given":"Vik","family":"Meadows","sequence":"additional","affiliation":[{"name":"Hepatology and Gastroenterology Division, Department of Medicine, Indiana University, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Hepatology and Gastroenterology Division, Department of Medicine, Indiana University, Indianapolis, IN 46202, USA"},{"name":"Department of Research, Richard L. 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