The Curious Case of Cholangiocarcinoma: Opportunities for Environmental Health Scientists to Learn about a Complex Disease

Abstract

Deaths from complex, noncommunicable diseases such as cancer are predicted to continue to increase worldwide, with low- and middle-income countries bearing the brunt of the burden. This problem requires a concentrated global effort to avoid devastating losses of life as well as economic losses. Cholangiocarcinoma (CCA) is a readily studied model of complex, noncommunicable disease, but it receives little attention outside of the scientific community in Southeast Asia. Here, we bring attention to the opportunity to study CCA as a model to understand the role of multiple, complex factors in cancer. These factors include allostatic load, individual genetic susceptibility, and environmental exposures such as chemicals, diet, socioeconomic factors, and psychosocial stress. The study of CCA offers a unique opportunity to make novel observations that could advance progress in prevention and intervention approaches for prevalent diseases that involve complex, multifactorial interactions.

Molecular Pathogenesis of Cholangiocarcinoma

“…Exposure to chemical toxins has been linked to outbreaks of cholangiocarcinoma in Italy, West Virginia, and British Columbia, although convincing evidence is lacking [82]. Possible culprits include dioxins, vinyl chloride, nitrosamines, asbestos, the oral contraceptive pill and isoniazid [36, 83, 84].…”

Tumor de Klatskin en el adulto

“… Tóxinas: los tóxicos y fármacos como el acholol, tabaco, nitrosamidas, metildopa, asbestos e isoniazida, están considerados como factores predisponente para el desarrollo de esta neoplasia (12).…”

An Insight into the Novel Immunotherapy and Targeted Therapeutic Strategies for Hepatocellular Carcinoma and Cholangiocarcinoma

“…In western countries is closely associated with chronic inflammation of the biliary tract, such as primary sclerosing cholangitis (PSC), biliary lithiasis, metabolic diseases, as well as chronic hepatic inflammatory diseases, including viral hepatitis B and C, NASH, mainly for intrahepatic cholangiocarcinogenesis. In Eastern countries, two well-demonstrated risks factor is a parasitic infection with larvae of Opisthorchis viverrini, and Clonorchissinesis via food consumption, as well as exposure to aflatoxins [ 7 , 8 ], which is also associated with HCC development. There is a notable association of anatomical sub-entities including, FGFR gene fusions, mutant IDH1/2, ARID1A, and BRAF genes in intrahepatic CCAs (iCCAs), while for extrahepatic tumors mutations in ELF3, IDH1/2, as well as PRKACA/B and FGFER fusions, while, TP53 and KRAS mutations are also reported for both subtypes [ 9 , 10 ].…”