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

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.

Keywords:

• Asbestos
• esophageal cancer
• causal analysis
• epidemiology
• toxicology
• mechanism of action

Acknowledgments

The authors thank Xintong He for her assistance with the epidemiological study quality analysis. The authors also thank Laura Smith and Kathryn Landoe for their assistance in editing and preparing this manuscript for submission. The authors appreciated the comments of the reviewers selected by the Editor and anonymous to the authors: they were useful in revising the manuscript.

Declaration of interest

Mr. Michael Peterson has served as an expert in multiple litigation matters involving asbestos-containing products. Some of the underlying research and analysis for this paper was performed during the context of those engagements and was sponsored by the defendant (Rockwell Automation). Neither the law firms nor the defendant in those matters, however, asked that this paper be written or published. The preparation of this manuscript was supported only by the authors’ employer (Gradient, an environmental health and risk sciences consulting firm), and its conclusions are exclusively those of the authors. Aside from the authors and internal Gradient reviewers, no one has commented on or revised this manuscript prior to its submission. It is possible the results of this evaluation will be used in the context of future litigation.

Supplemental material

Supplemental material for this article is available online here.

Notes

1 Note that meta-analyses were not formally evaluated for study quality.

2 Vehicle controls were not included for the gavage exposures. Therefore, an increased risk of esophageal cancer due to the procedure itself, which has been associated with reflux (Damsch et al. 2011), cannot be ruled out.

3 ROS are electrochemically unstable oxygen molecules that can react with biological macromolecules (e.g. lipid membrane, enzymes, and DNA). The hydroxyl radical is one of the most reactive ROS and is primarily formed in the presence of iron via the Fenton reaction (Gregus 2008).