Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case-control analysis

Our plain-English summary of Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case-control analysis, by G. Brandi, S. Di Girolamo, A. Farioli, et al (Cancer Causes & Control, 2013).

The study

• Authors: G. Brandi, S. Di Girolamo, A. Farioli, F. de Rosa, S. Curti, A.D. Pinna, G. Ercolani, F.S. Violante, G. Biasco, S. Mattioli
• Journal: Cancer Causes & Control
• Published: 2013;24(5):911-8
• Cited by: 49 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Purposes: We conducted a case-control analysis to explore the association between occupational exposure to asbestos and cholangiocarcinoma (CC).

Methods: The study was based on historical data from 155 consecutive patients with CC [69 intrahepatic CC (ICC) and 86 extrahepatic CC (ECC)] referred to Sant'Orsola-Malpighi University Hospital between 2006 and 2010. The cases were individually matched by calendar period of birth, sex, and region of residence to historical hospital and population controls. Occupational exposure to asbestos was retrospectively assessed considering job titles obtained from work histories. Separate conditional logistic regression models were applied for ECC and ICC. Estimates were adjusted for smoking status and socioeconomic class.

Results: We matched 149 controls (median birth year: 1947; males: 56 %) to 41 cases of ICC (median birth year: 1946; males: 56 %) and 212 controls (median birth year: 1945; males: 48 %) to 59 cases of ECC (median birth year: 1945; males 51 %); 53 cases were not matched due to residence or birth year. We found an increased risk of ICC in workers exposed to asbestos (adjusted OR 4.81, 95 % CI 1.73-13.33); we also observed suggestive evidence that asbestos exposure might be associated with ECC (adjusted OR 2.09, 95 % CI 0.83-5.27). Sensitivity analysis restricted to patients from the Province of Bologna produced confirmatory figures.

Conclusions: Our findings suggest that ICC could be associated with asbestos exposure; a chronic inflammatory pathway is hypothesized. Exposure to asbestos could be one of the determinants of the progressive rise in the incidence of ICC during the last 30 years.

In plain English

This Italian case-control analysis examined whether occupational exposure to asbestos was linked to cholangiocarcinoma (bile duct cancer). It analysed the intrahepatic form (inside the liver) and the extrahepatic form separately. Cases were patients referred to Sant'Orsola-Malpighi University Hospital, Bologna, in 2006-2010. After exclusions, 41 intrahepatic cases were matched to 149 controls and 59 extrahepatic cases to 212 controls taken from three earlier studies. Two raters who did not know who was a case or a control reviewed job histories. They counted as exposed anyone who had held at least one potentially exposed job. Among intrahepatic cases, 13 of 41 had held such a job, compared with 17 of 149 controls (adjusted odds ratio 4.81, 95% CI 1.73-13.33). For extrahepatic cases the adjusted odds ratio was 2.09 (95% CI 0.83-5.27), which the authors described as suggestive but weakly supported statistically. An analysis limited to Bologna gave similar results. The authors concluded that intrahepatic cholangiocarcinoma could be associated with asbestos exposure, possibly through chronic inflammation. They noted possible referral bias, small numbers, exposure judged after the fact (often from relatives' reports), and little information on other risk factors.

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 case-control analysis using hospital cases and historical controls from earlier studies, analysed with conditional logistic regression
• Who was studied: 155 consecutive patients with histologically confirmed cholangiocarcinoma (69 intrahepatic, 86 extrahepatic) referred to Sant'Orsola-Malpighi University Hospital, Bologna, Italy, January 2006 to December 2010. After exclusions (mainly region of residence), 41 intrahepatic cases were matched to 149 controls and 59 extrahepatic cases to 212 controls. Controls came from three earlier case-control studies (population controls, hospital controls and ophthalmic outpatients) and were matched by birth period, sex and region of residence.
• Exposure: Occupational asbestos exposure (fiber type not specified), judged from job titles and calendar periods. A subject counted as exposed after at least one potentially exposed job, treated as exposed versus not exposed; no cumulative dose was estimated. Two raters unaware of case/control status made the judgement. 54 subjects were classified as exposed, including construction workers (11), plumbers (7), road machine operators (7) and auto mechanics/brake specialists (5).
• Main results:
  • Intrahepatic cholangiocarcinoma: 13 of 41 cases (31.7%) versus 17 of 149 matched controls (11.4%) were classified as exposed to asbestos. Adjusted odds ratio 4.81 (95% CI 1.73-13.33); unadjusted 4.16 (95% CI 1.67-10.39).
  • Extrahepatic cholangiocarcinoma: 11 of 59 cases (18.6%) versus 21 of 212 matched controls (9.9%) were classified as exposed. Adjusted odds ratio 2.09 (95% CI 0.83-5.27), described by the authors as suggestive but with only weak statistical evidence.
  • No association was seen between intrahepatic cholangiocarcinoma and smoking or socioeconomic status. Extrahepatic cholangiocarcinoma likewise showed no clear association with either.
  • Sensitivity analysis restricted to the Province of Bologna (unadjusted only). Intrahepatic: 6 of 20 cases versus 9 of 80 controls exposed, odds ratio 3.41 (95% CI 1.01-11.54). Extrahepatic: 4 of 32 cases versus 11 of 121 controls exposed, odds ratio 1.37 (95% CI 0.40-4.67). The authors judged these in line with the main analysis.
  • Most cases had none of the listed known risk factors for cholangiocarcinoma: 22 intrahepatic cases (44%) and 41 extrahepatic cases (69%).
• The authors' conclusion: The authors concluded that their findings support the hypothesis that intrahepatic cholangiocarcinoma could be associated with asbestos exposure, possibly through a chronic inflammatory pathway. They saw suggestive evidence of an association with extrahepatic cholangiocarcinoma. They plan a larger population-based study to confirm this.
• Limitations the authors state:
  • The study population could be prone to referral bias, because cases came from a referral center and controls were historical.
  • 53 cases were excluded because they could not be matched, leaving a small number of cases.
  • Exposure was assessed retrospectively, so misclassification cannot be excluded. Occupational histories came from relatives for 46% of cases.
  • Data on controls were collected 6-10 years before data on cases.
  • Information on possible confounders was poor. For controls there was no information on established or putative risk factors such as hepatitis B and C, cirrhosis or alcohol intake. Smoking was classified only as never/ever.
  • Exposure could only be treated as exposed versus not exposed. A cumulative dose could not be reliably estimated from job titles.

Topics

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

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)
• 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)
• Mesothelin expression is a prognostic factor in cholangiocellular carcinoma — R. Nomura, H. Fujii, et al. (2013)
• Cholangiocarcinoma and Occupational Exposure to Asbestos: Insights From the Italian Pooled Cohort Study — S. Curti, M. Gallo, et al. (2024)

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