Lobe of origin in the attribution of lung cancer to asbestos

Lung cancer originates most commonly in the upper lobes in the general population but among workers with asbestosis it is most common in the lower lobes. Published data on lobar distribution were used to estimate the probabilities that lung cancer among asbestos workers is attributable to exposure to asbestos. This attribution varies directly with the relative risk. Critical values of the relative risk at which attribution of lung cancer to asbestos equalled its attribution to other causes, mainly smoking, were calculated. At a relative risk above 2.81 upper lobe cancers were more likely to be due to asbestos than not. For middle and lower lobe cancers, the critical relative risk was 1.55. These critical values were compared with published standardised mortality ratios reported for cohorts of workers with asbestosis. Since the ratios ranged from 6.3 to 9.1, the probability that lung cancer in such cases is due to asbestos is high regardless of lobe of origin. In many cohorts unstratified by the presence or absence of asbestosis the risk ratios are below one or both of these critical values. Since risk ratios are so high among workers with asbestosis, the ratios must be lower for workers without asbestosis than the overall ratios for unstratified cohorts. Therefore, the critical values may be useful in workers without asbestosis among such cohorts to estimate the upper limit of the probability that lung cancer in a given lobe is due to exposure to asbestos.     

Does asbestosis increase the risk of lung cancer?

Summary The question of whether asbestos workers with or without asbestosis have the same risk of lung cancer has not been adequately addressed in the literature. Studies of asbestos workers indicate that clinical symptoms and abnormal lung X-rays are more frequent among smokers than non-smokers, and some studies show that workers with asbestosis compared to those without asbestosis are more likely to be smokers or ex-smokers. Since smoking has a large affect on the risks of lung cancer, smoking habits should be considered when evaluating the risk of lung cancer among persons with and without asbestosis. Some studies show that the risk of lung cancer is higher for persons with asbestosis compared to persons without asbestosis, but none of these studies also considered the combined effects of smoking and asbestos exposure on the risk of lung cancer. It is unlikely that the higher risk of lung cancer to persons with asbestosis is only due to their higher prevalence of smoking. Some studies have suggested that asbestos workers with asbestosis may have a higher risk of lung cancer, but no definite conclusions can be drawn since dose-response relations were not evaluated. Further studies are needed to evaluate the interrelationships of smoking, asbestosis and the risk of lung cancer.     

Asbestosis and lobar site of lung cancer

OBJECTIVE—To assess the evidence for the hypothesis that lung cancer has a predilection for the lower lobes in workers with asbestosis.
METHOD—A review of the available literature with relevant information.
RESULTS—Six published reports were analysed. In four studies limited to series of cases with diagnoses of asbestosis, three showed lower lobe predominance of lung cancer whereas the fourth study included cases in which the radiographic readings did not meet the usual criterion of profusion for asbestosis. One cohort study showed lower lobe predominance; the other reported only 33% lower lobe cancers compared with 20% in unexposed controls.
CONCLUSION—There is some support for the hypothesis but more studies are needed.


Keywords: asbestos; asbestosis; lung cancer     

Incidence of cancer among the participants of the Finnish Asbestos Screening Campaign

OBJECTIVES: Cancer risk has been estimated for asbestos production workers or other heavily exposed asbestos workers in numerous studies. The bulk of the asbestos epidemic results come, however, from past intermittent exposures during asbestos product use. This study concentrated on estimating the risk of cancer in such a population. METHODS: Altogether 23285 men and 930 women invited to a nationwide screening campaign for benign asbestos-related diseases in 1990-1992 were followed for cancer through the Finnish Cancer Register up to 1998. Standardized incidence ratios (SIR) were calculated in comparison with the total Finnish population. RESULTS: Altogether 1392 cases of cancer were found among the men. The risk was slightly, but significantly elevated for lung cancer [SIR 1.14, 95% confidence interval (95% CI) 1.01-1.26), mesothelioma (SIR 2.77, 95% CI 1.66-4.31), and prostate cancer (SIR 1.21, 95% CI 1.09-1.34). The risk of lung cancer was slightly higher among the invited nonparticipants (SIR 1.48, 95% CI 1.20-1.79) than among the participants (SIR 1.02, 95% CI 0.88-1.17). About 98% of the lung cancers occurred in current or ex-smokers. CONCLUSIONS: In a population of long-term construction workers, the risk of lung cancer and mesothelioma was increased, but considerably lower than among insulators, asbestos sprayers, or patients with asbestosis. As it was not possible to follow most of the invited nonparticipants in the original screening study, selection bias by smoking or other life-style factors possibly correlated to the individual's decision to participate in the health screening cannot be excluded.     

Exposure to asbestos and lung and pleural cancer mortality among pulp and paper industry workers

We studied the mortality from lung and pleural cancers in a cohort of 62,937 male workers employed for at least 1 year in the pulp and paper industry in 13 countries during 1945 to 1996. Mill departments were classified according to probability and level of exposure to asbestos on the basis of available dust measurements and mill-specific information on exposure circumstances. Thirty-six percent of workers were classified as ever exposed to asbestos. Standardized mortality ratios of lung cancer were 0.99 (95% confidence interval [CI], 0.90 to 1.08) among unexposed and 1.00 (95% CI, 0.90 to 1.11) among ever exposed workers. The number of pleural cancer deaths among unexposed workers was 10; that among exposed workers was 14, most of which occurred among maintenance workers. In internal analyses, a trend in mortality from either neoplasm was suggested for estimated cumulative exposure to asbestos, weighted for the individual probability of exposure within the department and for duration of exposure (relative risk for lung cancer for 0.78+ f/cc-years, as compared with < or = 0.01 f/cc-years: 1.44; 95% CI, 0.85 to 2.45; corresponding relative risk for pleural cancer: 2.43; 95% CI, 0.43 to 13.63). Despite a possible nondifferential misclassification of exposure and outcome, this study suggests that the carcinogenic effect of asbestos can be detected among workers employed in industries such as the pulp and paper industry, in which it is not considered to be a major hazard.     

Mortality and morbidity among the working population of anthophyllite asbestos miners in Finland

Meurman, L. O., Kiviluoto, R., and Hakama, M. (1974).British Journal of Industrial Medicine,31, 105-112. Mortality and morbidity among the working population of anthophyllite asbestos miners in Finland. A study has been made in Finland of the effects of anthophyllite asbestos on mortality and morbidity of 1 092 asbestos workers first employed at two mines between 1936 and 1969; 95% of workers were traced, 248 of whom had died. A similar number of age-sex-matched controls was selected from a township 60 km from the mines. The causes of death included an excess due to lung cancer and asbestosis, but cancers of the digestive system occurred in equal frequency, and neither the cases nor controls had any confirmed mesotheliomas. Assuming a multiplicative effect of asbestos and smoking, the relative risk of lung cancer was 17 for an asbestos worker who smokes in terms of a non-exposed non-smoker. The corresponding figures were 12 for a smoker without asbestos exposure and 1·4 for an asbestos worker who did not smoke. More heavy smokers were found among the asbestos workers than among the controls. A threefold excess of dyspnoea and a twofold excess of cough were recorded for the asbestos workers compared with the controls after adjustment for smoking.     

单纯接触温石棉人员癌症死亡队列研究的荟萃分析

目的　用荟萃 (meta)分析探讨单纯接触温石棉人员的癌症是否高发。方法　凡满足明确是单纯温石棉暴露且为癌症死亡率队列研究的资料均被纳入研究对象 ,以直接法与随机效应模型法计算主要部位癌症的标准化死亡比 (SMR)及其 95 %可信区间 ,计算Q统计量与Z值检验研究结果异质性及其来源。结果　共有 2 6个队列符合入选标准 ,平均间皮瘤死亡百分比为 0 4 2 % ,全死因、全癌亡、呼吸系统全癌、肺癌和胃癌的meta SMR显著上升 ,分别为 1 2 8、1 2 6、2 2 4、2 2 9与1 2 7。肺癌的meta SMR在纺织 (3 6 4 )、石棉制品加工 (3 0 7)、采选矿 (2 2 4 )和石棉水泥制品加工(1 2 2 )显著升高 ,胃癌的meta SMR在石棉制品加工 (1 4 8)显著升高。其余部位癌症的meta SMR均无显著意义。结论　单纯温石棉暴露能使作业人员肺癌、间皮瘤显著高发 ,与其他部位癌症似无病因联系。     

Asbestosis as a precursor of asbestos related lung cancer: results of a prospective mortality study

A prospective mortality study of 839 men employed in the manufacture of asbestos cement products in 1969 examined lung cancer risk in relation to lung fibrosis seen on chest x ray film, controlling for age, smoking, and exposure to asbestos. Twenty or more years after hire, no excess of lung cancer was found among workers without radiographically detectable lung fibrosis, even among long term workers (greater than or equal to 21.5 years); nor was there a trend in risk by level of cumulative exposure to asbestos among such workers. By contrast, employees with small opacities (greater than or equal to 1/0; ILO classification) experienced a significantly raised risk of lung cancer (nine observed deaths v 2.1 expected), even though their exposures to asbestos were similar to the exposures of long term workers without opacities. In this population, excess risk of lung cancer was restricted to workers with x ray film evidence of asbestosis, a finding consistent with the view that asbestos is a lung carcinogen because of its fibrogenicity.     

The effect of asbestosis on lung cancer risk beyond the dose related effect of asbestos alone

Aims: To determine if the presence of asbestosis is a prerequisite for lung cancer in subjects with known exposure to blue asbestos (crocidolite). Methods: Former workers and residents of Wittenoom with known amounts of asbestos exposure (duration, intensity, and time since first exposure), current chest x ray and smoking information, participating in a cancer prevention programme (n = 1988) were studied. The first plain chest radiograph taken at the time of recruitment into the cancer prevention programme was examined for radiographic evidence of asbestosis according to the UICC (ILO) classification. Cox proportional hazards modelling was used to relate asbestosis, asbestos exposure, and lung cancer. Results: Between 1990 and 2002 there were 58 cases of lung cancer. Thirty six per cent of cases had radiographic evidence of asbestosis compared to 12% of study participants. Smoking status was the strongest predictor of lung cancer, with current smokers (OR = 26.5, 95% CI 3.5 to 198) having the greatest risk. Radiographic asbestosis (OR = 1.94, 95% CI 1.09 to 3.46) and asbestos exposure (OR = 1.21 per f/ml-year, 95% CI 1.02 to 1.42) were significantly associated with an increased risk of lung cancer. There was an increased risk of lung cancer with increasing exposure in those without asbestosis. Conclusion: In this cohort of former workers and residents of Wittenoom, asbestosis is not a mandatory precursor for asbestos related lung cancer. These findings support the hypothesis that it is the asbestos fibres per se that cause lung cancer, which can develop with or without the presence of asbestosis.     

Asbestosis as a precursor of asbestos related lung cancer: results of a prospective mortality study.

A prospective mortality study of 839 men employed in the manufacture of asbestos cement products in 1969 examined lung cancer risk in relation to lung fibrosis seen on chest x ray film, controlling for age, smoking, and exposure to asbestos. Twenty or more years after hire, no excess of lung cancer was found among workers without radiographically detectable lung fibrosis, even among long term workers (greater than or equal to 21.5 years); nor was there a trend in risk by level of cumulative exposure to asbestos among such workers. By contrast, employees with small opacities (greater than or equal to 1/0; ILO classification) experienced a significantly raised risk of lung cancer (nine observed deaths v 2.1 expected), even though their exposures to asbestos were similar to the exposures of long term workers without opacities. In this population, excess risk of lung cancer was restricted to workers with x ray film evidence of asbestosis, a finding consistent with the view that asbestos is a lung carcinogen because of its fibrogenicity.     

Epidemiology of occupational asbestos-related diseases in China

In 1950s and 60s, asbestosis had been a major health hazard for asbestos exposed workers. In the late 1970s, lung cancers with or without asbestosis were found among asbestos workers. All cohort studies on asbestos workers and on chrysotile miners in China showed excess deaths from lung cancer. In a large scale of cohort study on asbestos workers, a synergistic effect was found between cigarette smoking and asbestos exposure in the production of lung cancer. There have been not so many cases of malignant mesotheliomas reported, so far. In the cohort of chrysotile miners, 4 cases of pleural mesothelioma were observed. In the large scale of cohort study on asbestos workers in 9 factories using only chrysotile only one case of pleural mesothelioma was detected for 10 years' observation. In another 2 cohort studies, 2 cases of peritoneal mesotheliomas were found, one in Shanghai asbestos factory where a small amount of crocidolite had been used in 1960s, and one in Anqing asbestos factory that was located near tremolite mine. Further study is needed especially for the relationship between exposure to Chinese chrysotile and malignant mesotheliomas.     

中国石棉接触人员癌症死亡队列研究的Meta分析

目的以M eta分析探讨单纯接触温石棉人员癌症是否高发。方法凡满足明确是中国石棉接触人员且为癌症死亡率队列研究的资料均被纳入研究对象,以直接法与随机效应模型法计算主要部位癌症标准化死亡比(SMR)及其95%可信区间(CI),计算Q统计量与Z值检验研究结果异质性及其来源。结果共有13个队列符合入选标准,平均间皮瘤死亡百分比为0.62%,全死因、全癌亡、肺癌的M eta-SMR显著上升(分别为1.51、1.96、4.54),单纯接触温石棉人员肺癌的M eta-SMR也显著上升(4.39),消化系统、喉、乳腺和生殖泌尿系统等其他部位癌症的M eta-SMR未见显著上升。结论单纯温石棉暴露能使作业人员肺癌、间皮瘤显著高发,与其他部位癌症无病因联系。     

Lung cancer risk in past asbestos workers a few decades after exposure cessation and prospects for screening

To ascertain whether the current risk of lung cancer in former asbestos workers was higher than in the general population, 1,557 past asbestos workers were recruited during statutory health examinations (from 2000 onward) and followed up for mortality. Standardized mortality ratios (SMRs) were calculated. Poisson regression was used to adjust the rate ratios (RRs) for confounders. SMR was about 1.00 in workers with or without pleural plaques and 4.62 (95% confidence interval: 0.61–18.1) in those with asbestosis. Adjusted RRs for lung cancer were 4.70 (0.99–22.5) for asbestosis, 4.35 (0.97–19.5) for former smokers, 6.82 (1.38–34.4) for current smokers. Currently, lung cancer mortality in past asbestos workers is similar to the general population, probably because workers more exposed /more susceptible could have died from lung cancer before the beginning of follow-up.     

Study of asbestos bodies in Japanese urban patients

To study whether low-level exposure to asbestos contributes to lung cancer risk, the asbestos body (AB) content in lung tissue was measured in 476 patients with lung cancer and 369 patients with other diseases, all from a Japanese industrialized city. Eleven patients with histologically confirmed asbestosis were included. The findings were stratified into four groups. A significant number of patients with lung cancer were seen in the groups with high counts, as compared to controls. There was no significant difference in histologic type and site of lung cancer among four groups. The patients with lung cancer in high count groups were significantly younger than those with lower counts. A significant number of smokers were seen in the groups with high AB counts among patients with lung cancer as compared to controls, even if the patients with asbestosis were excluded. These findings suggest that there may be a positive interaction of smoking and exposure to asbestos relative to the incidence of lung cancer even at a low exposure level.     

Cancer incidence and mortality among Finnish asbestos sprayers and in asbestosis and silicosis patients

Cohorts of Finnish asbestos sprayers and of asbestosis and silicosis patients were followed for cancer with the aid of the Finnish Cancer Registry in the period 1967–1994. Compared with the cancer incidence of the total Finnish population, asbestos sprayers had an increased risk for total cancer (standardized incidence ratio [SIR] 6.7, 95% confidence interval [95% CI] 4.2–10); lung cancer (SIR 17, 95% CI 8.2–31); and mesothelioma (SIR 263, 95% CI 85–614). The SIR of the asbestosis patients was 3.7 (95% CI 2.8–5.0) for all sites, 10 (95% CI 6.9–14) for lung cancer, and 65 (95% CI 13–188) for mesothelioma. The silicosis patients also had significantly high SIR values for all sites (1.5, 95% CI 1.0–2.1) and lung cancer (2.7, 95% CI 1.5–4.5). The values for the SIR and the standardized mortality ratio for all sites and lung cancer were very similar, and therefore it seems that both are reliable indicators of the occurrence of occupational cancer. It was concluded that pneumoconioses patients and asbestos-exposed workers have a markedly elevated risk for cancer. Asbestos-induced occupational cancers are not only diseases of the elderly, since the relative risk is high also for middle-aged people. Am. J. Ind. Med. 31:693–698, 1997. © 1997 Wiley-Liss, Inc.     

Exposure-response analysis of risk of respiratory disease associated with occupational exposure to chrysotile asbestos.

OBJECTIVES: To evaluate alternative models and estimate risk of mortality from lung cancer and asbestosis after occupational exposure to chrysotile asbestos. METHODS: Data were used from a recent update of a cohort mortality study of workers in a South Carolina textile factory. Alternative exposure-response models were evaluated with Poisson regression. A model designed to evaluate evidence of a threshold response was also fitted. Lifetime risks of lung cancer and asbestosis were estimated with an actuarial approach that accounts for competing causes of death. RESULTS: A highly significant exposure-response relation was found for both lung cancer and asbestosis. The exposure-response relation for lung cancer seemed to be linear on a multiplicative scale, which is consistent with previous analyses of lung cancer and exposure to asbestos. In contrast, the exposure-response relation for asbestosis seemed to be nonlinear on a multiplicative scale in this analysis. There was no significant evidence for a threshold in models of either the lung cancer or asbestosis. The excess lifetime risk for white men exposed for 45 years at the recently revised OSHA standard of 0.1 fibre/ml was predicted to be about 5/1000 for lung cancer, and 2/1000 for asbestosis. CONCLUSIONS: This study confirms the findings from previous investigations of a strong exposure-response relation between exposure to chrysotile asbestos and mortality from lung cancer, and asbestosis. The risk estimates for lung cancer derived from this analysis are higher than those derived from other populations exposed to chrysotile asbestos. Possible reasons for this discrepancy are discussed.     

Occupational respiratory cancer and exposure to asbestos: A case-control study in a cohort of workers in the electricity and gas industry

Cancers of the pleura, lung, and larynx between 1978 and 1989 among active male workers of Electricité de France-Gaz de France were studied in association with asbestos exposure using a case-control design nested within the cohort of workers of the company. The cohort included about 1,400,000 person-years, corresponding to a mean of 117,000 men per year. Exposure to asbestos and to some potential occupational confounders selected among agents from groups I, IIa, and IIb of the International Agency for Research on Cancer was assessed by a job-exposure matrix specific to the company. During the observation period, 12 cases of pleural cancer, 310 cases of lung cancer, and 116 cases of larynx cancer were registered in the cancer register of the company social security department. Four controls per case, matched for year of birth, were randomly selected among the cohort. Conditional logistic regression was used to estimate the odds ratios. A first analysis was conducted in order to assess the validity of the job-exposure matrix by investigating already known relationships between asbestos exposure and asbestosis. For asbestosis, a strong exposure-response relation was found with an odds ratio (OR) of 57.4 [95% confidence interval (CI): 17.0–194.0] in the highest exposure group. There was an elevated risk of pleural cancer (OR, 4.8, CI, 1.2–19.8). For lung cancer, significant ORs of 2.0 (CI, 1.3–3.2) and 1.9 (CI, 1.2–3.0) were found among the two highest cumulative exposure groups; adjustement for confounders slightly decreased the ORs. Squamous cell neoplasm of the lung was associated with asbestos exposure. The association between larynx cancer and asbestos exposure showed a tendency towards a nonsignificant increase in ORs in the highest cumulative exposure categories; this tendency disappeared when adjusting for occupational confounders. This study showed that occupational exposure to asbestos could increase the risk of pleural and lung cancer in a sector in which exposure levels are not considered to be high compared with other industrial settings.     

Study of occupational lung cancer in asbestos factories in China.

A retrospective cohort study (1972-81) of occupational cancers in asbestos (chrysotile) factories has been previously published. In this paper the results of continued tracing and interviewing of members of this cohort from 1982 to 1986 is reported. The cohort included 5893 persons (45,974 person-years for men and 39,445 person-years for women). Malignant tumours played a large part in causes of death (36.9%). There were 183 cancers and 67 lung cancers among 496 deaths. The mortality due to lung cancer had a tendency to increase. By comparison with a control group, the RR of lung cancer was 5.32 (p < 0.01), and the SRR of lung cancer was 4.2 (p < 0.01), significantly higher than those of a control group. Among 148 cases of death from asbestosis there were 33 cases complicated with lung cancer (22.3%). The dose-response relations between exposure to asbestos and incidence of asbestosis and lung cancer were also studied in one asbestos factory. There was a positive correlation. A synergistic effect was found between cigarette smoking and lung cancer. Preventive and control measures and exposure limits for asbestos dust in the air of workplaces were recommended.     

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.     

Prediction of mesothelioma, lung cancer, and asbestosis in former Wittenoom asbestos workers.

Projections have been made of the number of mesotheliomas, lung cancers, and cases of asbestosis that might occur over the period 1987 to 2020 in former workers at the Wittenoom crocidolite asbestos mine in Western Australia. Predictions were based on the observed mortality to the end of 1986 and modelling of the mesothelioma rate. Elimination of crocidolite from the lungs was included in the model. Between the years 1987 and 2020 it is predicted that between 250 and 680 deaths will occur due to mesothelioma. This wide range is due to uncertainty on the functional form of the relation between mesothelioma rate and time, and insufficient data to estimate the elimination rate of crocidolite from the lungs. The most likely range is the lower half of this total range--that is, between 250 and 500. It is predicted that between 340 and 465 deaths will occur due to lung cancer. About 45% of these deaths would be attributable to exposure to asbestos. It is estimated that currently there are up to 200 cases of undiagnosed asbestosis. Of these about 50 will die of lung cancer or mesothelioma and are therefore also included in the figures above. Up to 60 former workers may develop the first signs of asbestosis in the future but any such cases are likely to progress to more serious disease at a much slower rate than the cases that have already been identified.