Asbestos as a systemic carcinogen: the evidence from eleven cohorts

Most known occupational carcinogens are site-specific, which implies that they are "complete" carcinogens with both "initiating" and "promoting" properties (Berenblum's terminology). Excess cancer at gastrointestinal sites among cohorts occupationally exposed to asbestos has been interpreted as reflecting additional site-specific effects, although excess at other sites has also been observed in some studies. The hypothesis that excess cancer at gastrointestinal sites cannot be distinguished from excess cancer at all nonpulmonary sites is tested by data from New York-New Jersey insulation workers working in 1943; similar workers employed after 1943; U.S.-Canadian insulation workers; London factory workers, male and female; Quebec miners and millers; retired U.S. factory workers; U.S. shipyard insulators; Italian shipyard workers in Genoa; Amosite factory workers; and U.S. factory workers. Excluding lung cancer and mesothelioma, observed-expected ratios for nonpulmonary cancer mortality range from 0.97 to 2.78, and do not differ significantly from gastrointestinal ratios. A dose-response gradient is observed for both ratios, when dose is estimated from lung cancer ratios, or in some studies, measured exposures. Site-specificity is unlikely for nonpulmonary cancer associated with asbestos exposure more than 20 years previously. Systemic carcinogenesis may be an example of promotion or impairment by asbestos of some cancer defense mechanism; immunological mechanisms have been suggested by Turner-Warwick and Parkes. Prospective studies are indicated.