Asbestos and Intrahepatic Cholangiocarcinoma

Our plain-English summary of Asbestos and Intrahepatic Cholangiocarcinoma, by G. Brandi, S. Tavolari (Cells, 2020).

The study

• Authors: G. Brandi, S. Tavolari
• Journal: Cells
• Published: 2020;9(2)
• Type of article: Review
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The link between asbestos exposure and the onset of thoracic malignancies is well established. However epidemiological studies have provided evidences that asbestos may be also involved in the development of gastrointestinal tumors, including intrahepatic cholangiocarcinoma (ICC). In line with this observation, asbestos fibers have been detected in the liver of patients with ICC. Although the exact mechanism still remains unknown, the presence of asbestos fibers in the liver could be explained in the light of their translocation pathway following ingestion/inhalation. In the liver, thin and long asbestos fibers could remain trapped in the smaller bile ducts, particularly in the stem cell niche of the canals of Hering, and exerting their carcinogenic effect for a long time, thus inducing hepatic stem/progenitor cells (HpSCs) malignant transformation. In this scenario, chronic liver damage induced by asbestos fibers over the years could be seen as a classic model of stem cell-derived carcinogenesis, where HpSC malignant transformation represents the first step of this process. This phenomenon could explain the recent epidemiological findings, where asbestos exposure seems mainly involved in ICC, rather than extrahepatic cholangiocarcinoma, development.

In plain English

This article was a review. The authors summarized published research on asbestos and intrahepatic cholangiocarcinoma (ICC), a cancer of the bile ducts inside the liver. They noted that most cohort studies of asbestos-exposed workers had no separate data on ICC. In a case-control study from Bologna, Italy, the odds ratio for ICC among people occupationally exposed to asbestos for over 30 years was 4.81 (95% CI 1.73-13.33). A Nordic case-control study found an increased risk for ICC, but not for cancer of the bile ducts outside the liver. Its odds ratio for ICC at the highest cumulative exposure was 1.7 (95% CI 1.1-2.6). Another research group detected chrysotile in the liver of five of seven ICC patients from Casale Monferrato. The authors described their own case-control study (168 cases, 185 controls), giving no risk estimates, and a gene-sequencing study without numerical results. As a hypothesis, they proposed that fibers trapped in small bile ducts could transform liver stem cells. The authors concluded that recent studies provide evidence of a link between asbestos exposure and ICC risk. They noted such studies were few.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: narrative review
• Who was studied: No new population was studied. The review covered published cohort studies of asbestos-exposed workers, two case-control studies of cholangiocarcinoma, and tissue studies of asbestos fibers in the liver and biliary tract.
• Exposure: Asbestos exposure in general, mostly occupational. The tissue studies reviewed reported chrysotile, and also crocidolite in the gallbladders of patients with malignant pleural mesothelioma.
• Main results:
  • Most reviewed cohort studies of asbestos-exposed workers gave estimates for liver cancers as a broad category, without specific data on ICC.
  • Earlier Bologna case-control study (69 ICC and 86 extrahepatic cases, 2006 to 2010): the odds ratio for ICC was 4.81 (95% CI 1.73-13.33) among those occupationally exposed for over 30 years. For extrahepatic cholangiocarcinoma the odds ratio was 2.09 (95% CI 0.83-5.27), described as limited evidence.
  • Nordic case-control study (1458 ICC and 3972 extrahepatic cases in Finland, Iceland, Norway and Sweden): ICC risk, but not extrahepatic cholangiocarcinoma risk, increased with cumulative asbestos exposure. The odds ratio for ICC was 1.7 (95% CI 1.1-2.6) at 15.0 or more fibers/mL x years.
  • A tissue study by another research group detected chrysotile fibers or bundles in five of seven ICC patients (71%) from Casale Monferrato, Italy.
  • The authors' own case-control study (CARA) recruited 168 cholangiocarcinoma cases (116 ICC, 52 extrahepatic) and 185 hospital controls and was presented at a 2018 congress. The authors said it confirmed the link, but this article gives no risk estimates from it.
  • In the authors' clinical experience, more than 40% of ICC patients diagnosed without any known risk factor were classed as asbestos-exposed by the ReNaM questionnaire.
  • In the authors' gene-sequencing study (EtherBil), asbestos-exposed ICC patients showed a distinctive molecular profile compared with patients not exposed. No numerical results are given.
  • The authors proposed, as a hypothesis, that thin and long fibers trapped in the smaller bile ducts (canals of Hering) could cause malignant transformation of liver stem/progenitor cells.
• The authors' conclusion: The authors concluded that recent epidemiological studies provide evidence of a link between asbestos exposure and ICC risk, and that this link may partly explain the global increase in this disease.
• Limitations the authors state:
  • Few epidemiological studies exist on ICC and asbestos exposure.
  • Most cohorts lacked the statistical power and diagnostic information needed to study ICC.
  • Changing disease coding, and possible misdiagnosis of ICC as other cancers, complicate the data.
  • The findings of fibers in the liver and biliary tract are preliminary, and the mechanism is not yet known.

Topics

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, Translocation, STEM, Carcinogenic, Malignant Transformation, Carcinogenesis.

Related studies

• Exposure to Asbestos and Increased Intrahepatic Cholangiocarcinoma Risk: Growing Evidences of a Putative Causal Link — G. Brandi, K. Straif, et al. (2022)
• Asbestos exposure as an additional risk factor for small duct intrahepatic cholangiocarcinoma: a pilot study — F. Vasuri, M. Deserti, et al. (2023)
• New insights into the molecular pathogenesis of intrahepatic cholangiocarcinoma — T. Patel (2014)
• Intrahepatic cholangiocarcinoma development in a patient with a novel BAP1 germline mutation and low exposure to asbestos — G. Brandi, M. Deserti, et al. (2020)
• Cholangiocarcinoma and Occupational Exposure to Asbestos: Insights From the Italian Pooled Cohort Study — S. Curti, M. Gallo, et al. (2024)
• Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case-control analysis — G. Brandi, S. Di Girolamo, et al. (2013)

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