Relationship between lung asbestos fiber type and concentration and relative risk of mesothelioma. A case-control study

Abstract

Lung tissue from 221 definite and probable cases of malignant mesothelioma reported to the Australian Mesothelioma Surveillance Program from January 1980 through December 1985 and from an age-sex frequency matched control series of 359 postmortem cases were examined by light microscopic (LM) and analytical transmission electron microscopic (TEM) analysis and energy dispersive x-ray analysis (EDAX). Concentrations of total fibers (coated and uncoated) (LM), crocidolite, amosite, chrysotile, and unidentified amphibole (TEM) (fibers/g dry lung tissue) were measured. Fiber concentrations less than 10 microns in length and greater than or equal to 10 microns in length were separately quantified. By comparing cases (221) and controls (359 LM, 103 TEM), odds ratios for increasing fiber concentrations compared with less than 15,000 fibers/g (LM) and less than 200,000 fibers/g (TEM) (the respective detection limits) were calculated. Univariate analyses showed statistically significant dose-response relationships between odds ratio and fiber concentration for all fiber concentration measures. The relationship between log(odds ratio) and log(fiber concentration) was linear. Multiple logistic regression analysis showed that a model containing crocidolite greater than or equal to 10 microns, amosite less than 10 microns, and chrysotile less than 10 microns as explanatory variables best described the data. The odds ratios for a X10 increase in fiber concentration (fibers/micrograms) were as follows: crocidolite greater than or equal to 10 microns, 29.4 (95% confidence interval [CI], 3.6 to 241); chrysotile less than 10 microns, 15.7 (95% CI, 6.1 to 40); amosite less than 10 microns, 2.3 (95% CI, 1.0 to 5.3). An additive risk model gave similar results. In a subgroup of cases and controls with only chrysotile in the lungs, a significant trend in odds ratio with increasing fiber content was found.

Relative risk of mesothelioma associated with different levels of exposure to asbestos.

“…In the comparison with the lung fiber concentration of the reference group of autopsy patients, the concentration of 1 million fibers/g of dry tissue, as an indicator of occupational exposure to asbestos, gave a relative risk estimate of 14.4 for the men, a value similar to the levelassociated tralian study of 221 definite and probable cases of mesothelioma and 359 autopsy referents statistically significant dose-response relationships were found between the odds ratio and the lung fiber concentration (23). In fiber analysis with TEM, the odds ratio for increased concentrations, in comparison with < 200 000 fibers/g of dry tissue, was calculated.…”

Asbestos-Related Research: First Objectivity then Conclusions

“…Furthermore, it was commented that "Bernstein and colleagues completely ignored the human lung burden studies that refute their conclusion about the short biopersistence of chrysotile"; more details and references are in [67]. Statistically significant doseresponse relationships between the odds ratios for mesothelioma and concentrations of asbestos fibers of different types were reported [68]. In particular, in the group with only chrysotile fiber in the lungs, a statistically significant trend of an increasing relative risk of mesothelioma with increasing fiber content was demonstrated [68].…”

“…Statistically significant doseresponse relationships between the odds ratios for mesothelioma and concentrations of asbestos fibers of different types were reported [68]. In particular, in the group with only chrysotile fiber in the lungs, a statistically significant trend of an increasing relative risk of mesothelioma with increasing fiber content was demonstrated [68]. This paper was not cited in [41,55].…”

“…Further reports [69,70] on persistence of chrysotile fibers in the lungs and/or their possible association with Mt and lung cancer, not cited in [41,55], were discussed in [67]. In the author reply [71], the arguments from [67] have not been adequately responded, being dismissed by a declaration that the studies [68,69] "appear to support the concepts put forward by Bernstein et al" followed by self-references [71]. Other reports and reviews [43][44][45][46][47][48]51,56,58,63,[72][73][74][75], not supporting the authors' concept, are also not cited in the voluminous reviews [41,55].…”

Letter to the Editor re Bernstein et al: Health risk of chrysotile revisited. Crit Rev Toxicol, 2013; 43(2): 154–183

“…No controls were observed to have chrysotile fibers greater than 20 mm in length in their lungs; these long chrysotile fibers were detected among 20-25% of the occupationally exposed. Rogers et al (1991) analysed lung tissue from 221 definite and probable cases of malignant mesothelioma reported to the Australian Mesothelioma Surveillance Program and compared the lung fiber burden to a control series of 359 postmortem cases. Univariate analyses showed statistically significant dose-response relationships between the odds ratio for mesothelioma and fiber concentration for all fiber concentration measures.…”