Cholangiocarcinoma Attributed to Occupation: A Systematic Reviews

Our plain-English summary of Cholangiocarcinoma Attributed to Occupation: A Systematic Reviews, by A. Seeherunwong, N. Chaiear, N. Khuntikeo, et al (Asian Pacific Journal of Cancer Prevention, 2022).

The study

• Authors: A. Seeherunwong, N. Chaiear, N. Khuntikeo, C. Ekpanyaskul
• Journal: Asian Pacific Journal of Cancer Prevention
• Published: 2022;23(6):1837-1845
• Type of article: Systematic review
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The occurrence of a cluster of occupational cholangiocarcinoma(CCA) cases among Japanese workers at a small offset printing plant led to the hypotheses that occupational exposure was the root cause of this cancer. Numerous workplace carcinogens can be found at various jobs sites and are integral to various industrial processes. Therefore, a systematic evaluation of potential occupationally-related CCA and likely exposure types is needed.

Objective: To conduct a systematic review on the cause of CCA in relation to occupation.

Methods: The systematic review included papers published between 1980 and 2020. Databases included PubMed, Science Direct, CINAHL, ProQuest Medical Library, Springer, Wiley online library, and the Cochrane library. The review focused on CCA, intrahepatic CCA(as distinct from other types of liver cancer), and extrahepatic CCA(not including the gallbladder). While some occupations involve an expected risk of exposure to carcinogens, this study sought both primary reports on specific carcinogens or surrogates by occupation or industry title. Of the 65 English version abstracts, 18 studies were selected for in-depth review according to the eligibility criteria. Two occupational physicians independently assessed the relevance to the study objectives, data extractability, and data quality as per the Newcastle-Ottawa Scale.

Results: The review revealed that ten observational studies met the eligibility criteria. There was heterogeneity of occupational exposure assessment and the reported results. The possible carcinogens statistical significantly related to the incidence or mortality of CCA risk included 1,2-dichloropropane (the highest RR = 32.40, 95%CI=6.40-163.90), asbestos (the highest OR=4.81, 95 % CI =1.73-13.33), endocrine-disrupting compounds (the highest OR =2.00, 95% CI=1.10-3.70), and rotating shift work (the highest HR =1.97, 95%CI=1.02-3.79). These carcinogens are classified as IARC class 1 and 2A.

Conclusions: Despite the limited number of studies reviewed, the hypothesis of occupational risk for CCA was supported. Occupational health and safety measures may decrease exposure to these carcinogens, and surveillance in high-risk occupations or industries is urgently needed to prevent and control CCA.

In plain English

This was a systematic review, not a new study. The authors searched several databases for English-language articles from 1980 to December 2020 on work and cholangiocarcinoma (bile duct cancer), either inside the liver (intrahepatic) or outside it (extrahepatic, excluding the gallbladder). Ten observational studies passed their eligibility and quality checks. Because the studies differed, the results were not pooled.

On asbestos, an Italian case-control study (Brandi et al., 2013) reported an adjusted odds ratio of 4.81 (95% CI 1.73 to 13.33) for intrahepatic cancer with occupational asbestos exposure. For extrahepatic cancer the figure was 2.09 (95% CI 0.83 to 5.27). A Nordic case-control study (Farioli et al., 2018) looked at cumulative exposure above 15 fibres/mL x years. It reported an odds ratio of 1.7 (95% CI 1.1 to 2.6) for intrahepatic cancer and 1.1 (95% CI 0.8 to 1.4) for extrahepatic cancer. A Swedish study reported a standardized incidence ratio of 10.60 (p less than 0.05) for extrahepatic cancer among male construction insulation workers.

Other reviewed studies linked 1,2-dichloropropane, endocrine-disrupting compounds and rotating shift work to this cancer. The authors concluded that these four were statistically significantly related to cholangiocarcinoma risk. They cautioned that designs and exposure assessment varied, and that cases and 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: Systematic review of observational studies, with a narrative (non-pooled) summary
• Who was studied: Ten observational studies (three case-control, six cohort, one cross-sectional) published between 1980 and December 2020, mostly from Europe (especially the Nordic countries) and Japan, on intrahepatic and extrahepatic cholangiocarcinoma (gallbladder excluded)
• Exposure: Any occupational exposure: agents, mixtures, exposure circumstances or job titles. Asbestos was among the agents found; the article does not name specific fiber types.
• Main results:
  • Brandi et al. (2013), Italy (100 cases: 41 intrahepatic, 59 extrahepatic; 2006-2010): occupational asbestos exposure and intrahepatic CCA, adjusted OR 4.81 (95% CI 1.73 to 13.33)
  • Brandi et al. (2013): occupational asbestos exposure and extrahepatic CCA, adjusted OR 2.09 (95% CI 0.83 to 5.27)
  • Farioli et al. (2018), Finland, Norway, Sweden and Iceland (8,231 CCA cases, 1960-2005): cumulative asbestos exposure above 15 f/mL x years and intrahepatic CCA, OR 1.7 (95% CI 1.1 to 2.6)
  • Farioli et al. (2018): same exposure level and extrahepatic CCA, OR 1.1 (95% CI 0.8 to 1.4; p for trend 0.503)
  • Malker et al. (1986), Sweden (764 biliary tract cancer cases excluding gallbladder, 1961-1979): men who were insulation workers in the construction industry had an extrahepatic CCA SIR of 10.60 (p less than 0.05)
  • Kumagai et al. (2016), 95 printing company workers in Osaka, Japan: high cumulative 1,2-dichloropropane exposure (5-year lag) and CCA, adjusted RR 32.4 (95% CI 6.4 to 163.9)
  • Ahrens et al. (2007), men in six European countries: high exposure to endocrine-disrupting compounds and extrahepatic CCA, adjusted OR 2.00 (95% CI 1.10 to 3.70)
  • Lin et al. (2015), Japanese men: rotating shift work and death from extrahepatic CCA, adjusted HR 1.97 (95% CI 1.02 to 3.79)
• The authors' conclusion: The authors concluded that four occupational carcinogens were statistically significantly related to CCA risk: 1,2-dichloropropane (or co-exposure with dichloromethane), asbestos, endocrine-disrupting compounds, and rotating shift work. They said the findings require careful interpretation.
• Limitations the authors state:
  • Variation in study designs and occupational exposure assessments made the studies heterogeneous and a meta-analysis difficult
  • Only English-language, full peer-reviewed articles were included, so relevant studies in other languages may have been missed
  • Inconsistent CCA classification, with registries often combining CCA with other liver and gallbladder cancers, may hinder interpretation
  • Only a few cases and studies were available

Topics

Medical terms in this study, explained in our Lexicon: Systematic Review, Occupational Exposure, IARC.

Related studies

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

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