Lung cancer and asbestos exposure: Asbestosis is not necessary

Recent commentaries on the issue of asbestos-related lung cancer have raised important points. One major question is whether lung cancer can be attributed to asbestos exposure in the absence of asbestosis. This review attempts to place the debate in the proper context for establishing causation. Relevant epidemiologic and pathologic studies are analyzed, as well as the scientific basis for each position in the debate. The assertion that asbestosis must be present in order to attribute a lung cancer to asbestos exposure does not meet accepted standards for establishing causation. In addition, some evidence has been incorrectly cited in support of this position. This discussion can benefit from clearer definitions of asbestosis, a more thorough evaluation of the available scientific information, and a proper context for determining causation. This review of the available evidence indicates that lung cancers can occur as a result of asbestos exposure, in the absence of clinical or histologic asbestosis. Causation in an individual should be assessed by considering duration of exposure, intensity of exposure, and appropriate latency. © 1996 Wiley-Liss, Inc.     

Asbestosis and tuberculosis

The frequent association between silicosis and tuberculosis has been known for a long time. However, the possible interrelationship between asbestosis and tuberculosis is not entirely clear, and some reports on the subject are contradictory. The incidence of tuberculosis was determined in three groups of people: 1) those with asbestosis, 2) those exposed to asbestos dust but without asbestosis, and 3) healthy people without pneumo-coniotic exposure. Chest X-rays of 2,846 workers surveyed in this department between 1976 and 1980 were reviewed. Since only one case of active tuberculosis was detected, residual tuberculosis was the type encountered and this was diagnosed solely on its radiological signs. The incidence of tuberculosis was: 3.87% (N = 257) for group 1; 3.45% (N = 1,215) in group 2; and 3.93% (N = 1,374) for group 3. Statistical analysis confirms the lack of significant differences in the incidence of tuberculosis in the three groups. From these findings, it is concluded that asbestosis is not an influential factor in the appearance and development of tuberculosis.     

Autopsy Cases of Asbestosis in Japan: A Statistical Analysis on Registered Cases

There are 525 (484 male, 38 female, 3 unknown) autopsy cases with asbestosis registered in the Annual of the Pathological Autopsy Cases in Japan, which is issued by the Japanese Society of Pathology for the years 1958-1996. The frequency of asbestosis (number of cases/total autopsy cases) was 0.017% (76/440,334) for the 1958-1979 time period, 0.058% (226/390,124) for 1980-1989, and 0.099% (223/225,801) for 1990-1996. There was a significant increase in asbestosis cases across the three time periods (p < .0001). The number of asbestosis cases increased markedly among individuals who worked with asbestos products, as well as among those employed in asbestos-processing factories. The frequency of malignant tumors associated with asbestosis was 61.0% (320/525), and the frequency also increased across the three time periods, from 43.4% (33/76) to 62.8% (142/226) and 65.0% (145/223), respectively. Among the 525 cases with asbestosis, there were 174 lung cancers (33.1%), 73 malignant mesotheliomas (13.9%), 29 stomach cancers (5.5%), 14 liver cancers (2.7%), 9 prostatic cancers (1.7%), 8 malignant lymphomas (1.5%), 6 laryngeal cancers (1.1%), 4 pancreas cancers (0.8%), 3 rectal cancers (0.6%), and 28 other cancers (5.3%). The frequencies of lung cancer, malignant mesothelioma, and laryngeal cancer were significantly higher in the cases with asbestosis than among the nonasbestosis cases. The number of malignant tumors related to asbestos exposure is expected to increase in the future.     

Electron microscopy analysis of mineral fibers in human lung tissue.

In the present study, lung samples from 126 autopsied cases were examined to determine the content of mineral fibers using analytical transmission electron microscopy (ATEM). The cases were divided into four groups (22 lungs of persons exposed to ambient environmental pollution, 32 cases of mesothelioma, 38 cases of primary lung cancer, and 34 asbestosis cases, 13 of these with additional pleural plaques). Fibers were counted, measured, and mineralogically identified using a combination of X-ray microanalysis and electron diffraction of the non-oriented fiber. Concentration of fibrous particles (defined as particles above 1 micron in length with roughly parallel long sides and an aspect ratio of 5:1 and greater) was calculated as fibers 10(6)/g dry lung weight. The concentration of chrysotile was found to be similar throughout the groups except for two cases in the asbestosis group with comparably high numbers of chrysotile. However, a remarkable difference for amphiboles could be observed between the groups. Asbestos bodies were mostly found in the asbestosis group. There was a rather good correlation between numbers of amphibole fibers and asbestos bodies, with an average ratio of 10:1. For comparison purposes between occupationally exposed/non-exposed individuals, a transition was found in the concentration range of 3-10(7) asbestos fibers/g dried lung weight.     

Exposures and mortality among chrysotile asbestos workers. Part II: mortality

A retrospective cohort mortality study was conducted among a cohort of 1,261 white males employed one or more months in chrysotile asbestos textile operations and followed between 1940 and 1975. Statistically significant excess mortality was observed for all causes combined (standardized mortality ratio [SMR] = 150), lung cancer (SMR = 135), diseases of the circulatory system (SMR = 125), nonmalignant respiratory diseases (SMR = 294), and accidents (SMR = 134). Using estimated fiber exposure levels in conjunction with detailed worker job histories, exposure-response relationships were investigated. Strong exposure-response relationships for lung cancer and asbestos related non-malignant respiratory diseases were observed. Compared with data for chrysotile miners and millers, chrysotile textile workers were found to experience significantly greater lung cancer mortality at lower lifetime cumulative exposure levels. Factors such as differences in airborne fiber characteristics may partially account for the large differences in exposure response between textile workers and miners and millers.     

The risk of lung cancer with increasing time since ceasing exposure to asbestos and quitting smoking

Objectives

To examine if the risk of lung cancer declines with increasing time since ceasing exposure to asbestos and quitting smoking, and to determine the relative asbestos effect between non‐smokers and current smokers.

Methods

A cohort study of 2935 former workers of the crocidolite mine and mill at Wittenoom, who responded to a questionnaire on smoking first issued in 1979 and on whom quantitative estimates of asbestos exposure are known. Conditional logistic regression was used to relate asbestos exposure, smoking category, and risk of lung cancer.

Results

Eighteen per cent of the cohort reported never smoking; 66% of cases and 50% of non‐cases were current smokers. Past smokers who ceased smoking within six years of the survey (OR = 22.1, 95% CI 5.6 to 87.0), those who ceased smoking 20 or more years before the survey (OR = 1.9, 95% CI 0.50 to 7.2), and current smokers (<20 cigarettes per day (OR = 6.8, 95% CI 2.0 to 22.7) or >20 cigarettes per day (OR = 13.2, 95% CI 4.1 to 42.5)) had higher risks of lung cancer compared to never smokers after adjusting for asbestos exposure and age. The asbestos effect between non‐smokers and current smokers was 1.23 (95% CI 0.35 to 4.32).

Conclusion

Persons exposed to asbestos and tobacco but who subsequently quit, remain at an increased risk for lung cancer up to 20 years after smoking cessation, compared to never smokers. Although the relative risk of lung cancer appears higher in never and ex‐smokers than in current smokers, those who both smoke and have been exposed to asbestos have the highest risk; this study emphasises the importance of smoking prevention and smoking cessation programmes within this high risk cohort.     

Asbestos-related lung cancer mortality in Piedmont,Italy

This study investigates the association between pleural neoplasm mortality, a possible proxy for asbestos exposure, and lung cancer mortality among males resident in Piedmont (northwestern Italy). Pleural neoplasm mortality was estimated in the 1,209 municipalities of the region for the period 1980–1992, applying Bayesian methods. The association with lung cancer mortality for municipalities was studied using Poisson regression. Urban/rural indicators and altitude were also included in the analysis. A positive, statistically significant association was found between pleural neoplasm and lung cancer mortality (β = 0.025, P < 0.001); lung cancer risk was associated also with urban status (vs. rural, β = 0.223,P < 0.001) and altitude (P = 0.01). The proportion of lung cancer deaths attributable to living in municipalities with increased pleural neoplasm mortality was 3.9% (95% confidence interval, 2.1–5.7%). The observed association and the presence of a dose-response relationship at the municipality level underscore the dangers of asbestos for human health. Am. J. Ind. Med. 33:565–570, 1998. © 1998 Wiley-Liss, Inc.     

石棉及电焊烟尘相关肺癌组织K-ras基因突变的研究

为了解石棉及电焊烟尘相关肺癌的Ｋ－ｒａｓ基因突变情况,并与非职业肺癌的Ｋｒａｓ基因突变特点比较,进一步探讨石棉及电焊烟尘的致癌机理。收集８例非职业肺癌组织、９例石棉相关肺癌组织及４例电焊烟片段长度多态性分析,单链构象多态性分析及ＤＮＡ真接测序分析。     

Professor Matthew Stewart: Asbestosis research 1929–1934

Matthew Stewart, Professor of Pathology at Leeds University, developed an interest in asbestosis during the late 1920s. In 1929, the Medical Research Council (MRC), encouraged by an advisory committee, funded research into asbestosis at Leeds University. Stewart supported by physicians designed a program of clinical, radiological and physiological studies to follow up Merewether's affected asbestos workers. Unfortunately, this met with opposition from industry, and the Home Office Factory Department was reluctant to assist, so it was abandoned. Industry did, however, cooperate with Stewart's studies on the effects of exposing guinea pigs in the factory environment, but this led to little in the way of publication. The failure of the Leeds School to realize its potential in investigating the effects of asbestos in humans, results in part from the discouragement it received and in part from the limited time and energies available to persons with a wide range of active interests. Some 45 years were to elapse before the MRC were enabled to carry out an analysis of the clinical, radiological and physiological data of a population of asbestos workers. Am. J. Ind. Med. 32:562–569, 1997. © 1997 Wiley-Liss, Inc.     

Radiographic asbestosis is not a prerequisite for asbestos-associated lung cancer in Ontario asbestos–cement workers

In recent years, controversy has developed about whether pre-existing asbestosis is a prerequisite for the diagnosis of asbestos-related lung cancer. This paper presents the results of a prospective study, in a cohort of Ontario asbestos–cement workers, of lung cancer in relation to radiographs obtained 20 and 25 years from first exposure to asbestos. Radiographs were interpreted by a single NIOSH-certified “B” reader, and asbestosis was defined to mean an ILO code of 1/0 or greater. There were 143 subjects (123 without asbestosis, 20 with asbestosis), with a radiograph available for interpretation at 20 years from first exposure or later. The lung cancer standardized mortality ratio (SMR) among men without asbestosis at 20 years latency was 5.53 (95%CI: 2.9–9.7). There were 128 subjects (114 without asbestosis, 14 with asbestosis) with a radiograph available for interpretation at 25 years from first exposure or later. The lung cancer SMR among men without asbestosis at 25 years latency was 5.81 (95%CI 2.7–11). The results of this study are consistent with those of epidemiologic studies of asbestos-exposed populations in a variety of exposure situations. These studies have demonstrated that lung cancer risk is elevated in the presence of radiographic asbestosis, but they have also shown that lung cancer risk may be elevated in the absence of radiographic asbestosis. Am. J. Ind. Med. 32:341–348, 1997. © 1997 Wiley-Liss, Inc.     

Chrysotile asbestos and health in Zimbabwe: II. Health status survey of active miners and millers.

As part of the effort to establish industrial practice and public policy regarding asbestos in Zimbabwe, we have conducted a cross-sectional study of the chrysotile mines and mills. A stratified random sample of workers with greater than 10 years of exposure has been evaluated by spirometry, chest radiographs, and employment history. The latter was converted to quantitative estimates of exposure dose, using a matrix based on measured and reconstructed fiber levels for each job and facility during the years of work. Based on these data, a clear dose-response between asbestos exposure and functional loss has been demonstrated, with mean losses from predicted of about 400-600 cc in vital capacity in the 10% of the population with heaviest exposures. Low-grade parenchymal radiographic abnormalities (ILO grade greater than or equal to 1/0) were evident in 8.7% of the total study group and were almost 10 times more common in those with more than 100 fibers/cc.years cumulative exposure than in those with 16 fibers/cc.years or less. Pleural disease was relatively rare, occurring in just under 10% of the study group, and was unrelated to exposure dose. Overall, these findings are compatible with results of similar studies in Quebec and Swaziland and suggest that similar control strategies are probably indicated.     

Insulation,asbestos, smoking habits,and lung cancer cell types

The association between occupational exposure to asbestos and histological type of lung cancer was analyzed in a multicenter hospital-based case-control study (2,871 male cases and 5,240 male controls) conducted from 1981-1991. Twenty-two percent of cases and 18% of controls were employed in asbestos-related occupations for at least 1 year. Most of these asbestos jobs were in the construction field. The odds ratio (OR) among current smokers was 1.0 [95% confidence intervals (CI) 0.9 to 1.3]; for ex-smokers, the OR was 1.4 (95% CI 1.1 to 1.6). In contrast, 10% of cases and 5% of controls self-reported that they were chronically exposed to asbestos for at least 1 year. Self-reported asbestos exposure was significantly related to all lung cancer cell types among smokers and ex-smokers, although a trend in the ORs with duration of self-reported exposure was not found for current smokers. Among 48 cases and 52 controls reporting distinct exposure to building insulation, the OR was 2.2 (95% CI 1.2 to 4.3) for current smokers, and 1.8 (95% CI 0.9 to 3.6) for ex-smokers, compared to subjects who were not exposed to building insulation and asbestos. A nonsignificant association with self-reported exposure to asbestos was observed for a small number of never smokers (eight of 83 nonsmoking cases, OR = 2.0, 95% CI 0.9 to 4.6). When examining these results and their causal implications, possible misclassification and reporting biases need to be considered.     

石蜡包埋的石棉肺癌组织的基因组DNA的快速提取法

建立了从少量石蜡包埋的组织切片中快速提取石棉肺癌组织中的基因组ＤＮＡ的水煮脱蜡法，克服了传统的二甲苯脱蜡法的周期长、成本高和毒性大的缺点。所得到的基因组ＤＮＡ中，长片段占较大的比例，总量可足够用作１０～２０次ＰＣＲ扩增反应的模板，并可用于其它分子生物学研究     

Occupational asbestos exposure and predictable asbestos-related diseases in India

BACKGROUND: India imports nearly 100,000 metric tons of asbestos per year, and small-scale asbestos (chrysotile and tremolite) mining and milling contributes nearly 5%-10% of the total national usage. The industry is relatively young, having started in the 1950s and 1960s. METHODS: Surveys of asbestos-exposed workers have identified significant occupational exposures, early pleural and parenchymal changes on chest radiograph, and decrements in lung function. RESULTS AND CONCLUSIONS: Based on knowledge of past and current exposures to asbestos in industry, we can predict a future occurrence of clinical asbestos-related diseases-pleural changes, pulmonary fibrosis, bronchogenic carcinoma, and diffuse malignant mesothelioma. These cases of asbestos related disease are expected to occur in asbestos exposed workers from mining, milling, and manufacturing as well as in those with secondary exposures to asbestos-containing materials, including construction and maintenance workers, users of asbestos-containing consumer products, and the occupants of asbestos-containing buildings.