Asbestos and colon cancer: a weight-of-the-evidence review.

What is the evidence that exposure to asbestos causes colon cancer? This weight-of-evidence review considers epidemiologic evidence from cohort studies of asbestos-exposed workers, case-control studies of colon cancer, animal bioassays, and other corroborative evidence. The major evidence for a causal association at high exposure is a combined colorectal standardized mortality ratio (SMR) of 1.5 for asbestos cohorts where the lung cancer SMR was greater than twofold. However, misdiagnosis may spuriously elevate the SMR. The strongest evidence against a causal association between colon cancer and asbestos exposure is the lack of an exposure-response gradient in asbestos cohorts where trends for lung cancer are observed. Population-based case-control studies of colon cancer do not show any consistent risk associated with asbestos exposure. Long-term ingestion studies show no evidence of an increased incidence of colon cancer in animals by this route of exposure and do not provide biological plausibility for a causal association between asbestos exposure and colon cancer.     

Asbestos and colon cancer: lack of association in a large case-control study.

Previous studies linking exposure to asbestos with human colon cancer have used mortality rather than incidence as their endpoint and have neither assessed nor controlled for confounding by diet, genetic factors, or other risk factors for colon cancer. A case-control study of 746 histologically confirmed cases of colon cancer and 746 matched neighborhood controls was conducted in Los Angeles County, California. In univariate analyses of the 419 male pairs, a weak association was found between asbestos exposure and colon cancer (odds ratio (OR) = 1.16, 95% confidence interval (CI) 0.80-1.69). When confounding by family history of large bowel cancer, diet, body weight, and physical activity was controlled, there was no association between colon cancer and exposure to asbestos among males (OR = 0.99, 95% CI 0.66-1.50). When asbestos exposure was restricted to occurrences preceding diagnosis by more than 15 years, there was no clear association between such exposure and colon cancer, either before (OR = 1.14, 95% CI 0.76-1.70) or after confounding was controlled (OR = 0.93, 95% CI 0.60-1.44). Further analyses by frequency and duration of exposure failed to show any association between asbestos and risk of colon cancer, but did show a consistent pattern of confounding by nonoccupational factors that, when controlled, invariably produced a weak protective effect of asbestos exposure. Among the 327 female pairs, only 6 cases and 11 controls reported asbestos exposure (OR = 0.55, 95% CI 0.20-1.48), and there was no evidence of risk increasing as the frequency or duration of exposure increased. This study suggests not only that occupational exposure to asbestos is not a risk factor for colon cancer in the general population of Los Angeles, but also that observed associations between asbestos and colon cancer should not be interpreted as causal unless confounding by nonoccupational factors has been evaluated and controlled.     

Asbestos cement dust inhalation by hamsters.

Two groups of 96 male Syrian golden hamsters were exposed to respirable asbestos cement aerosol at concentrations of approximately 1 and approximately 10 micrograms/liter, respectively, 3 hours/day, 5 days/week. Average fiber counts ranged from 5 to about 120 fibers/cm3. Each group was randomly divided into six subgroups of 16 animals. The first subgroup was sacrificed after 3 months of exposure, the second after 6 months, and the third after 15 months. The fourth subgroup was withdrawn from exposure after 3 months, observed for an additional 3 months, and then sacrificed. The fifth and sixth subgroups were withdrawn after 3 and 6 months of exposure, respectively, and maintained for observation up to the 15-month exposure point of the third subgroup at which time all surviving animals were sacrificed. All other experimental procedures were similar to those delineated in a previous publication describing the development of an animal model, techniques, and an exposure system for asbestos cement dust inhalation (A. P. Wehner, G. E. Dagle, and W. C. Cannon, 1978, Environ. Res. 16, 393-407). The asbestos cement exposures had no significant effect on body weight and mortality of the animals. Higher aerosol concentration and longer exposure times increased the number of macrophages and ferruginous bodies found in the lungs of the exposed animals. Recovery periods had no effect on the incidence of macrophages and ferruginous bodies. The incidence of very slight to slight fibrosis in the animals sacrificed after 15 months of exposure shows a significant (P less than 0.01) trend when the untreated control group and the 1 and 10 microgram/liter dose level groups are compared, indicating a dose-response relationship. Development of minimal fibrosis continued in animals withdrawn from exposure. No primary carcinomas of the lung and respiratory tract and no mesotheliomas were found.     

Asbestos bodies in bronchoalveolar lavage fluids of brake lining and asbestos cement workers.

Asbestos body (AB) concentrations in bronchoalveolar lavage samples of 15 brake lining (BL) workers exposed only to chrysotile have been determined and compared with those from 44 asbestos cement (AC) workers extensively exposed to amphiboles. The mean AB concentrations (263 +/- 802 and 842 +/- 2086 AB/ml respectively) for those groups did not differ significantly but were much higher than those found in control groups. Analytical electron microscopy of asbestos body cores showed that in the BL group 95.6% were chrysotile fibres whereas in the AC group amphiboles accounted for 93.1%. The size characteristics of the central fibres differed for chrysotile and amphibole AB, the former being shorter and thinner. Examination of repeated bronchoalveolar lavage samples showed that the mechanisms of clearance of chrysotile fibres do not affect AB concentration for at least 10 months after cessation of exposure. It thus appears that routine counting of ABs in BAL allows the assessment of current or recent occupational exposures to asbestos. Exposures to chrysotile lead to AB concentrations comparable with those encountered in exposures to amphiboles.