Critical review of the evidence for a causal association between exposure to asbestos and esophageal cancer

Our plain-English summary of Critical review of the evidence for a causal association between exposure to asbestos and esophageal cancer, by M.K. Peterson, I. Mohar, T. Lam, et al (Critical Reviews in Toxicology, 2019).

The study

• Authors: M.K. Peterson, I. Mohar, T. Lam, T.J. Cook, A.M. Engel, H. Lynch
• Journal: Critical Reviews in Toxicology
• Published: 2019;49(7):597-613
• Type of article: Review
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Esophageal cancers comprise about 1% of all cancers diagnosed in the US but are more prevalent in other regions of the world. Several regulatory agencies have classified asbestos as a known human carcinogen, and it is linked to multiple diseases and malignancies, including lung cancer and mesothelioma. In a 2006 review of the epidemiological literature, the Institute of Medicine (IOM) did not find sufficient evidence to demonstrate a causal relationship between asbestos exposure and esophageal cancer. To reevaluate this conclusion, we performed a critical review of the animal toxicological, epidemiological, and mechanism of action literature on esophageal cancer and asbestos, incorporating studies published since 2006. Although there is some evidence in the epidemiological literature for an increased risk of esophageal cancer in asbestos-exposed occupational cohorts, these studies generally did not control for critical esophageal cancer risk factors (e.g. smoking, alcohol consumption). Furthermore, data from animal toxicological studies do not indicate that asbestos exposure increases esophageal cancer risk. Based on our evaluation of the literature, and reaffirming the IOM's findings, we conclude that there is insufficient evidence to demonstrate a causal link between asbestos exposure and esophageal cancer.

In plain English

This article is a review, not a new study. The authors re-examined whether asbestos causes esophageal cancer, updating a 2006 Institute of Medicine review. They gathered animal studies and 36 human studies (4 case-control, 30 cohort and 2 meta-analyses). They quality-rated the individual human studies (not the two meta-analyses), classing as low quality any that adjusted for neither smoking nor drinking. In lifelong feeding studies in rats and hamsters given chrysotile, amosite, tremolite or crocidolite, esophageal cancer was seen in less than 1% of asbestos-fed animals. None of the case-control studies found a statistically significant increase. Of the 30 cohort studies of asbestos-exposed workers, 11 reported a statistically significant association, but only one of these adjusted for both smoking and alcohol. In several studies reporting raised risks, risk did not rise consistently with exposure. The authors found no studies on how asbestos might act in the esophagus specifically. They concluded that the evidence is insufficient to show that asbestos is a causal factor for esophageal cancer in humans. They noted that few human studies adequately addressed smoking and drinking.

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: Critical review of published animal, human (epidemiological) and mechanism studies on asbestos and esophageal cancer, with study quality ratings, combined into a causation analysis
• Who was studied: Published studies found through PubMed and Scopus, plus studies reviewed by IOM (2006), IARC (2012) and Li et al. (2016). These included 11 animal studies and 36 epidemiological studies (4 case-control, 30 cohort, 2 meta-analyses).
• Exposure: In animals: lifelong feeding of chrysotile, amosite, tremolite or crocidolite at 1% of the diet (NTP studies), plus some inhalation studies. In humans: occupational asbestos exposure, with fiber type often not reported.
• Main results:
  • In the NTP animal feeding studies, esophageal cancer was observed in less than 1% of animals exposed through feed only. It was observed in 0.5% of rats that were also given intermediate-range chrysotile by oral gavage. NTP concluded that the 1% asbestos diets were not carcinogenic in any tissue.
  • Only 11 of the 34 individual epidemiological studies adjusted for smoking and/or drinking. The other 23 were classed as low relative quality. The two meta-analyses were not formally rated.
  • None of the 4 case-control studies found a statistically significant increase in esophageal cancer with asbestos exposure.
  • Of the 30 cohort studies, 11 reported a statistically significant association between esophageal cancer and working in jobs with asbestos exposure. Only one of these (Offermans et al. 2014) adjusted for both smoking and alcohol.
  • In the Netherlands cohort (Offermans et al. 2014), men 'ever highly exposed' had an adjusted hazard ratio for esophageal adenocarcinoma of 2.52 (95% CI 1.01 to 6.26) compared with those 'never highly exposed'. The authors noted there was no significant increase and no exposure-response pattern when other exposure measures were used.
  • In the Chinese chrysotile miners (Lin et al. 2014), risk was highest in the middle exposure group rather than the highest (adjusted hazard ratio 20.26 vs 3.34). In the French cohort (Clin et al. 2017), the risk estimates by exposure category did not show a clear exposure-response pattern.
  • One meta-analysis (Li et al. 2016, 21 cohorts) found an SMR of 1.24 (95% CI 1.12 to 1.37). The other (Frumkin and Berlin 1988, 10 cohorts) found an SMR of 112 (95% CI 72 to 174), which was not a statistically significant excess. The authors placed very little confidence in either.
  • The authors reported that the human studies did not show a difference in esophageal cancer risk between chrysotile and amphibole exposure.
  • No studies were found on how asbestos might cause cancer in the esophagus specifically.
• The authors' conclusion: The authors concluded that there is insufficient evidence to show that asbestos exposure is a causal factor for esophageal cancer in humans, reaffirming the 2006 IOM conclusion.
• Limitations the authors state:
  • No studies directly investigated how asbestos affects the esophagus at the molecular level.
  • Few human studies controlled, or controlled adequately, for smoking and alcohol, the main esophageal cancer risk factors.
  • The quality ratings are relative. A 'low quality' study is not necessarily invalid.
  • The meta-analyses were not formally evaluated for study quality.
  • The gavage experiments had no vehicle controls, so an effect of the gavage procedure itself could not be ruled out.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Throat and laryngeal cancer.

Medical terms in this study, explained in our Lexicon: Esophageal Cancer, Lung Cancer, Mesothelioma, Asbestos Exposure.

Related studies

• Occupational exposures and risk of esophageal and gastric cardia cancers among male Swedish construction workers — C. Jansson, A.L. Johansson, et al. (2005)
• Occupational asbestos exposure and risk of esophageal, gastric and colorectal cancer in the prospective Netherlands Cohort Study — N.S. Offermans, R. Vermeulen, et al. (2014)
• Meta-Analysis of the Association between Asbestos Exposure and Esophageal Cancer — C.W. Wu, H.Y. Chuang, et al. (2021)
• Esophageal carcinoma with asbestos bodies — J.P. Parmar (1992)
• Epithelioid malignant mesothelioma presenting with features of esophageal tumor — M.W. Khalil, A.P. Campbell, et al. (2011)
• Occupational Exposures and Esophageal Cancer: Prog Study — A. Gressier, G. Gourier, et al. (2022)

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