Exposure to Asbestos and Increased Intrahepatic Cholangiocarcinoma Risk: Growing Evidences of a Putative Causal Link

Our plain-English summary of Exposure to Asbestos and Increased Intrahepatic Cholangiocarcinoma Risk: Growing Evidences of a Putative Causal Link, by G. Brandi, K. Straif, D. Mandrioli, et al (Annals of Global Health, 2022).

The study

• Authors: G. Brandi, K. Straif, D. Mandrioli, S. Curti, S. Mattioli, S. Tavolari
• Journal: Annals of Global Health
• Published: 2022;88(1):41
• Type of article: Review, Letter
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

To date the true global incidence of intrahepatic cholangiocarcinoma (iCCA) and the underlying risk factors remain to be fully defined, in particular, the role of occupational and environmental factors. Currently, the putative role of asbestos exposure as a risk factor for iCCA is gaining increased attention in the international scientific community and agencies. In this commentary we review and integrate available epidemiological and mechanistic evidences that support a potential role of asbestos exposure in iCCA etiology.

Copyright: © 2022 The Author(s).

In plain English

This article was a short commentary, published as a letter to the editor. The authors reviewed earlier studies on whether asbestos exposure is linked to intrahepatic cholangiocarcinoma (iCCA), a cancer of the bile ducts inside the liver. It reported no new data of its own. The authors described an Italian case-control study that found higher odds of iCCA in workers exposed to asbestos (OR 4.81, 95% CI 1.73 to 13.33). They also described a Nordic case-control study in which the odds rose with cumulative exposure, reaching an OR of 1.7 (95% CI 1.1 to 2.6) at 15.0 or more fibers/mL × years compared with never exposed. The authors said two cohort studies were hard to interpret because they did not separate iCCA from hepatocellular carcinoma. They cited reports of asbestos fibers found in the livers of iCCA patients, and a study that found BAP1 gene mutations more often in exposed than in non-exposed iCCA patients (27% vs 5%). They noted that finding fibers in the liver does not by itself show a causal link. The authors concluded that the evidence points to a putative causal role of asbestos that deserves further large studies.

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: Commentary (letter to the editor) reviewing previously published epidemiological, molecular and histological studies; no original data
• Who was studied: No study population of its own. It reviewed published cohort studies, case-control studies, fiber-detection studies, a genetic sequencing study and a case report on iCCA and asbestos.
• Exposure: Occupational and environmental asbestos exposure in general. The article does not name specific fiber types.
• Main results:
  • In a cited Italian case-control study (ref. 12), workers exposed to asbestos had increased odds of iCCA (OR = 4.81, 95% CI 1.73 to 13.33).
  • In the same cited Italian study, the authors described limited evidence for extrahepatic cholangiocarcinoma (eCCA) (OR = 2.09, 95% CI 0.83 to 5.27).
  • In a cited case-control study nested in the Nordic Occupational Cancer (NOCCA) cohort (Finland, Iceland, Norway, Sweden; 1 458 iCCA cases; ref. 13), iCCA risk increased with cumulative asbestos exposure. The OR was 1.7 (95% CI 1.1 to 2.6) for subjects with 15.0 or more fibers/mL × years compared with never exposed.
  • Selikoff et al. (ref. 9) reported a significant increase in deaths from gall bladder/bile duct cancer (RR = 2.42, p less than 0.01) among 17 800 asbestos insulation workers in the USA and Canada.
  • In a cited cohort of 4427 shipbreaking workers (ref. 10), the adjusted hazard ratio for cancer of the liver and intrahepatic bile ducts was 1.6 (95% CI 1.08 to 2.36).
  • In a cited cohort of 12578 asbestos-cement workers (ref. 11), the standardized mortality ratio for cancer of the liver and intrahepatic bile ducts was 0.99 (95% CI 0.81 to 1.20) in males and 0.87 (95% CI 0.42 to 1.60) in females.
  • Cited exploratory studies (refs. 14, 15) reported asbestos fibers in the liver of iCCA patients living in Casale Monferrato, an area of Italy with high environmental asbestos exposure.
  • A cited whole-exome sequencing study (ref. 23) found BAP1 somatic mutations more often in asbestos-exposed iCCA patients than in non-exposed patients (27% vs 5%, p = 0.0289).
  • A cited case report (ref. 24) described a 47-year-old patient who developed iCCA with no risk factors other than about 15 years of occupational exposure to low levels of asbestos. The patient also carried a BAP1 germline mutation.
• The authors' conclusion: The authors concluded that the epidemiological and mechanistic evidence points to a putative causal role of asbestos in iCCA. They said this deserves further investigation in large observational studies with accurate asbestos exposure assessment.
• Limitations the authors state:
  • The cited cohort studies did not distinguish iCCA from hepatocellular carcinoma, which makes their results difficult to interpret.
  • Detecting asbestos fibers in the liver is not by itself sufficient to support a causal link, because fibers have also been found in cancers not related to asbestos.
  • BAP1 alterations have also been found in cancer patients not occupationally exposed to asbestos, so further studies are needed on the role of BAP1.

Topics

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, Etiology.

Related studies

• 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)
• Asbestos and Intrahepatic Cholangiocarcinoma — G. Brandi, S. Tavolari (2020)
• Intrahepatic cholangiocarcinoma development in a patient with a novel BAP1 germline mutation and low exposure to asbestos — G. Brandi, M. Deserti, et al. (2020)
• Occupational exposure to asbestos and risk of cholangiocarcinoma: a population-based case-control study in four Nordic countries — A. Farioli, K. Straif, et al. (2018)
• Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case-control analysis — G. Brandi, S. Di Girolamo, et al. (2013)

Browse more research in Annals of Global Health, or return to medical research.