A cohort of some 11,000 men born 1891-1920 and employed for at least one month in the chrysotile mines and mills of Quebec, was established in 1966 and has been followed ever since. Of the 5351 men surviving into 1976, only 16 could not be traced; 2508 were still alive in 1989, and 2827 had died; by the end of 1992 a further 698 were known to have died, giving an overall mortality of almost 80%. This paper presents the results of analysis of mortality for the period 1976 to 1988 inclusive, obtained by the subject-years method, with Quebec mortality for reference. In many respects the standardised mortality ratios (SMRs) 20 years or more after first employment were similar to those for the period 1951-75--namely, all causes 1.07 (1951-75, 1.09); heart disease 1.02 (1.04); cerebrovascular disease 1.06 (1.07); external causes 1.17 (1.17). The SMR for lung cancer, however, rose from 1.25 to 1.39 and deaths from mesothelioma increased from eight (10 before review) to 25; deaths from respiratory tuberculosis fell from 57 to five. Among men whose exposure by age 55 was at least 300 million particles per cubic foot x years (mpcf.y), the SMR (all causes) was elevated in the two main mining regions, Asbestos and Thetford Mines, and for the small factory in Asbestos; so were the SMRs for lung cancer, ischaemic heart disease, cerebrovascular disease, and respiratory disease other than pneumoconiosis. Except for lung cancer, however, there was little convincing evidence of gradients over four classes of exposure, divided at 30, 100, and 300 mpcf.y. Over seven narrower categories of exposure up to 300 mpcf.y the SMR for lung cancer fluctuated around 1.27 with no indication of trend, but increased steeply above that level. Mortality form pneumoconiosis was strongly related to exposure, and the trend for mesothelioma was not dissimilar. Mortality generally was related systematically to cigarette smoking habit, recorded in life from 99% of survivors into 1976; smokers of 20 or more cigarettes a day had the highest SMRs not only for lung cancer but also for all causes, cancer of the stomach, pancreas, and larynx, and ischaemic heart disease. For lung cancer SMRs increased fivefold with smoking, but the increase with dust exposure was comparatively slight for non-smokers, lower again for ex-smokers, and negligible for smokers of at least 20 cigarettes a day; thus the asbestos-smoking interaction was less than multiplicative. Of the 33 deaths from mesothelioma in the cohort to date, 28 were in miners and millers and five were in employees of a small asbestos products factory where commercial amphiboles had also been used. Preliminary analysis also suggest that the risk of mesothelioma was higher in the mines and mills at Thetford Mines than in those at Asbestos. More detailed studies of these differences and of exposure-response relations for lung cancer are under way.
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We investigated apoptosis and the expression of bcl-2, mcl-1, bcl-X, and bax in histological sections from 35 malignant mesotheliomas and 21 metastatic adenocarcinomas. Moreover, the expression of bcl-2, mcl-1, bcl-X, and bax were assessed by Western blotting in nonmalignant human mesothelial cells (Met5A) and seven malignant cell lines. The apoptotic index in mesotheliomas was 1.07+/-1.14%. Patients with mesotheliomas showing a high apoptotic index (> or =0.75%) had a worse prognosis (P = 0.008). bcl-2 positivity was observed in only seven cases, but bcl-X, mcl-1, and bax positivity was seen in all of them. In immunoblotting experiments, all mesothelioma cell lines were negative for bcl-2 but positive for bcl-X, mcl-1, and bax. The apoptotic index in bcl-2-negative mesotheliomas was 1.25+/-1.24% and in bcl-2-positive ones, 0.47+/-0.42% (P = 0.014). The apoptotic index did not significantly associate with bcl-X, mcl-1, or bax expression (P = 0.19, P = 0.25, and P = 0.46, respectively). No significant difference was observed in apoptosis or expression of bcl-2, bcl-X, or bax between malignant mesotheliomas and metastatic adenocarcinomas. The former, however, showed more often weak mcl-1 immunoreactivity (P = 0.01). The results show that the extent of apoptosis may influence patient prognosis. bcl-2 is inversely associated with the apoptotic index but is relatively infrequently expressed in malignant mesotheliomas. Widespread expression of bcl-X, mcl-1, and bax suggests that these proteins may also take part in apoptosis regulation in mesotheliomas.
Asbestos has been widely used in the refinery and petrochemical sector. Mesothelioma has occurred among maintenance employees, and it was hypothesized that mesothelioma is a marker for exposures which might increase lung cancer risk. A death certificate-based case-control study of mesothelioma and lung cancer from 1980 to 1992 was conducted in an Ontario county with a substantial presence of these industries. Each of the 17 men who died of mesothelioma and 424 with lung cancer were matched with controls who died of other causes. The Job and Industry fields on the death certificates were abstracted. Employment as a maintenance worker in the refinery and petrochemical sector was associated with an increased risk of mesothelioma (odds ratio: 24.5; 90% confidence interval 3.1-102). The risk of lung cancer among petrochemical workers, in comparison with all other workers in the county, was 0.88. In an internal comparison of maintenance employees with other blue-collar workers in the refinery and petrochemical sector, the odds ratio for lung cancer was 1.73 (90% confidence interval 0.83-3.6). This finding is consistent with no difference in risk between maintenance and other employees, but it is also compatible with study power being too low to achieve statistical significance. The hypothesis of increased lung cancer risk could be examined more fully with nested case-control studies in existing cohorts. Meanwhile, it would be prudent to reinforce adherence to asbestos control measures in the refinery and petrochemical sector.
We compared death certificates for asbestos-associated diseases (mesothelioma, lung cancer, asbestosis) in two asbestos workers' cohorts. One (insulation workers) had current or recent employment and a strong, continuing union support system which gave them much information about the effects of asbestos exposure. The second cohort, asbestos factory workers, had no such advantage. The factory had closed almost 30 years before, and its workers had dispersed into many areas of the state and nation. Accuracy of medical diagnosis was comparable in the two groups, but occupational listings were not. Three-quarters of the insulators' death certificates told of asbestos work, while virtually none of the factory workers' certificates provided such information, even for deaths of mesothelioma and asbestosis. The data indicate that disease categories, based on medical and pathological diagnoses, at least for asbestos-associated disease, tend to be accurate. Attempts to identify groups at risk by sorting occupational categories can give variable results, good for those with current exposures, much less satisfactory for those with long-past occupational exposures.
Among a cohort of 544 men with at least 20 years of employment in chrysotile mining and milling at Thetford Mines, Canada, 16% of the deaths were from lung cancer and 15% from asbestosis. The excess over expected deaths from these causes account for 43 of 178 deaths in the group. The risk of death of asbestosis, at equal times fron onset of exposure, is very similar in miners and millers, factory workmen and insulators. The ratio of observed to expected deaths from lung cancer is similar in the miners and millers and factory workers, but higher in insulators. The risk of death of mesothelioma in miners and millers is decidedly less than the other two groups. The exact causes of the reduced risk in this category are not yet completely clarified.
There is ongoing argument about the potency of chrysotile asbestos to cause malignant mesothelioma. Risk assessment for chrysotile is influenced by the alleged absence of mesotheliomas among workers at the Raybestos Manhattan friction products plant in Connecticut, a plant that essentially used only chrysotile asbestos. Regrettably, the statement that there is an absence of mesothelioma deaths in the Connecticut plant is false. In this paper, we report on our review of the work histories and pathological reports of five individuals from the Connecticut plant who were diagnosed with mesothelioma. We discuss the Connecticut plant in relation to the most recent epidemiological information for chrysotile. Calculation suggests that mesothelioma rates at this plant were similar to those observed among Quebec miners and the South Carolina textile plant. We urge everyone concerned with the risk assessment of chrysotile asbestos to make use of all available data.
Comment In: Ann Occup Hyg. 2011 Aug;55(7):817-9; author reply 820-221831850