Cholangiocarcinoma and Occupational Exposure to Asbestos: Insights From the Italian Pooled Cohort Study

Our plain-English summary of Cholangiocarcinoma and Occupational Exposure to Asbestos: Insights From the Italian Pooled Cohort Study, by S. Curti, M. Gallo, D. Ferrante, et al (La Medicina del Lavoro, 2024).

The study

• Authors: S. Curti, M. Gallo, D. Ferrante, F. Bella, L. Boschetti, V. Casotto, M. Ceppi, D. Cervino, L. Fazzo, U. Fedeli, P. Giorgi Rossi, L. Giovannetti, P. Girardi, C. Lando, E. Migliore, L. Miligi, E. Oddone, V. Perlangeli, R. Pernetti, S. Piro, C. Storchi, R. Tumino, A. Zona, M. Zorzi, G. Brandi, S. Ferretti, C. Magnani, A. Marinaccio, S. Mattioli
• Journal: La Medicina del Lavoro
• Published: 2024;115(2):e2024016
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Recent studies supported the association between occupational exposure to asbestos and risk of cholangiocarcinoma (CC). Aim of the present study is to investigate this association using an update of mortality data from the Italian pooled asbestos cohort study and to test record linkage to Cancer Registries to distinguish between hepatocellular carcinoma (HCC) and intrahepatic/extrahepatic forms of CC.

Methods: The update of a large cohort study pooling 52 Italian industrial cohorts of workers formerly exposed to asbestos was carried out. Causes of death were coded according to ICD. Linkage was carried out for those subjects who died for liver or bile duct cancer with data on histological subtype provided by Cancer Registries.

Results: 47 cohorts took part in the study (57,227 subjects). We identified 639 causes of death for liver and bile duct cancer in the 44 cohorts covered by Cancer Registry. Of these 639, 240 cases were linked to Cancer Registry, namely 14 CC, 83 HCC, 117 cases with unspecified histology, 25 other carcinomas, and one case of cirrhosis (likely precancerous condition). Of the 14 CC, 12 occurred in 2010-2019, two in 2000-2009, and none before 2000.

Conclusion: Further studies are needed to explore the association between occupational exposure to asbestos and CC. Record linkage was hampered due to incomplete coverage of the study areas and periods by Cancer Registries. The identification of CC among unspecific histology cases is fundamental to establish more effective and targeted liver cancer screening strategies.

In plain English

This Italian study updated a pooled mortality study of workers formerly exposed to asbestos. It linked deaths from liver and bile duct cancer to Cancer Registry records to identify cholangiocarcinoma (bile duct cancer). It included 47 cohorts with 57,227 people (89.6% men), mostly from asbestos cement, rolling stock construction and maintenance, and shipyard or harbour work. Compared with regional rates, deaths from liver and intrahepatic bile duct cancer were not increased (men: SMR 1.02, 95%CI 0.94-1.11; women: SMR 0.98, 95%CI 0.68-1.35). Deaths from gallbladder and extrahepatic bile duct cancer were not increased either. Of 639 such deaths in 44 registry-covered cohorts, 240 were linked: 14 cholangiocarcinomas, 83 hepatocellular carcinomas, 117 with unspecified histology, 25 other carcinomas and one case of cirrhosis. Twelve of the 14 cholangiocarcinomas occurred in 2010-2019, and none before 2000. The authors noted incomplete registry coverage, small numbers, and no data on smoking, alcohol or other liver disease. They concluded that the high share of unspecified cases prevented firm support for a causal link between occupational asbestos exposure and cholangiocarcinoma, and that further studies are needed.

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: Exploratory study based on an update of a pooled mortality cohort study of Italian asbestos-exposed workers, with record linkage of liver and bile duct cancer deaths to Cancer Registry (or hospital discharge) records; standardized mortality ratios calculated against regional reference rates
• Who was studied: 47 of 52 Italian industrial cohorts of workers formerly exposed to asbestos (including a cohort of wives of Eternit asbestos cement workers and Italian crocidolite miners in Wittenoom, Australia): 57,227 subjects, 89.6% men (n=51,252); 44 cohorts in areas covered by Cancer Registries and three in the province of Bologna; follow-up ended between 2018 and 2021 depending on cohort, with analyses restricted to events after January 1st, 1970
• Exposure: Occupational asbestos exposure, mainly in asbestos cement (19 cohorts), rolling stock construction and maintenance (12 cohorts), and shipyard/harbour work (6 cohorts); fiber types listed by cohort include chrysotile, crocidolite, amosite and mixed fibres
• Main results:
  • Across the 47 cohorts, mortality from liver and intrahepatic bile duct cancer was not increased: men SMR 1.02 (95%CI 0.94-1.11), women SMR 0.98 (95%CI 0.68-1.35)
  • Mortality from gallbladder and extrahepatic bile duct cancer was also not increased: men SMR 0.93 (95%CI 0.76-1.14), women SMR 1.02 (95%CI 0.65-1.53)
  • Of 639 deaths from liver and bile duct cancer in the 44 registry-covered cohorts, 240 were linked to Cancer Registry: 14 cholangiocarcinoma (CC), 83 hepatocellular carcinoma (HCC), 117 with unspecified histology, 25 other carcinomas, and one case of cirrhosis
  • The 14 CC comprised nine intrahepatic, one extrahepatic, one involving both intrahepatic and extrahepatic bile ducts, and three not further classified
  • No CC were reported before 2000; two intrahepatic CC occurred in 2000-2009 and twelve CC in 2010-2019
  • Among the 14 CC cases, 13 were men; mean age 72.9 years (range 58-89), mean time since first exposure 45.4 years (range 30-70), mean duration of exposure 18.1 years (range 2-34)
  • In 2010-2019 the ratio of HCC to CC among linked cases was about 2.6 to 1, compared with an expected 8 to 1 reported in a separate study by Mancini et al
  • In the three Bologna cohorts (no Cancer Registry), 59 liver and bile duct cancer deaths were identified, of which 20 were linked to hospital discharge records
• The authors' conclusion: The authors concluded that record linkage to Cancer Registries was feasible but limited. They said the high proportion of cases with unspecified histology prevented firm support for a causal association between occupational asbestos exposure and CC, and that further studies, including multicentre case-control studies with microscopically verified cases, are needed.
• Limitations the authors state:
  • Cancer Registry coverage was incomplete and uneven in time and space, limiting identification of cases, especially those more than 20 years ago
  • For nearly 85% of cases the authors could not distinguish HCC from CC
  • The absolute numbers of CC were too small to evaluate a causal association
  • Changes in ICD-O classification over time caused some misclassification of intrahepatic and extrahepatic CC
  • No data were available on personal habits or medical conditions such as alcohol, smoking or other liver disease, which the authors said might overestimate CC risk
  • Other occupational substances may have contributed to CC

Topics

Medical terms in this study, explained in our Lexicon: Occupational Exposure, Cohort Study, Carcinoma, Histological Subtype, Cancer Registry, Histology.

Related studies

• 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)
• New insights into the molecular pathogenesis of intrahepatic cholangiocarcinoma — T. Patel (2014)
• Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case-control analysis — G. Brandi, S. Di Girolamo, et al. (2013)
• 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)
• Asbestos and Intrahepatic Cholangiocarcinoma — G. Brandi, S. Tavolari (2020)

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