Occupational exposure to asbestos and man-made vitreous fibres and risk of lung cancer: a multicentre case-control study in Europe

Objectives

To investigate the contribution of occupational exposure to asbestos and man‐made vitreous fibres (MMVF) to lung cancer in high‐risk populations in Europe.

Methods

A multicentre case‐control study was conducted in six Central and Eastern European countries and the UK, during the period 1998–2002. Comprehensive occupational and sociodemographic information was collected from 2205 newly diagnosed male lung cancer cases and 2305 frequency matched controls. Odds ratios (OR) of lung cancer were calculated after adjusting for other relevant occupational exposures and tobacco smoking.

Results

The OR for asbestos exposure was 0.92 (95% CI 0.73 to 1.15) in Central and Eastern Europe and 1.85 (95% CI 1.07 to 3.21) in the UK. Similar ORs were found for exposure to amphibole asbestos. The OR for MMVF exposure was 1.23 (95% CI 0.88 to 1.71) with no evidence of heterogeneity by country. No synergistic effect either between asbestos and MMVF or between any of them and smoking was found.

Conclusion

In this large community‐based study occupational exposure to asbestos and MMVF does not appear to contribute to the lung cancer burden in men in Central and Eastern Europe. In contrast, in the UK the authors found an increased risk of lung cancer following exposure to asbestos. Differences in fibre type and circumstances of exposure may explain these results.Lung cancer is the most common tumour worldwide, apart from non‐melanoma skin cancer, and remains one of the most fatal cancer types.¹ The causal relation between cigarette smoking and lung cancer is well established and in most populations over 90% of all male patients develop their disease following tobacco smoking.^2,3,4 A change in smoking habits in recent decades has resulted in a decline in lung cancer mortality in men in most European countries including Central and Eastern Europe and the UK.⁵ Nevertheless, Hungary and Poland are among the countries with the highest lung cancer mortality in the world.⁶ Environmental and occupational lung carcinogens also contribute to the global burden of lung cancer, but the quantification of their role is complex. Asbestos has been recognised as a human carcinogen for many years.^7,8 Consequently, mining and use of asbestos have been greatly reduced since 1990 and banned in most European countries. Even so, high levels of exposure to asbestos are still found in Central Europe and the former Soviet Union.⁹ Due to their persistence in the environment, asbestos fibres also remain in many work sites as well as in neighbouring areas where asbestos was used.^10,11 All commercial brands of asbestos, regardless of fibre type, are considered carcinogenic, but amphiboles (amosite, anthophyllite, crocidolite and tremolite) show greater carcinogenic potency than chrysotile.^12,13 Chrysotile is by far the most common type worldwide and the only asbestos type mined in Europe today, mainly in Russia. In the 1970s amphibole asbestos from South Africa and other countries was used in over 50 countries, including UK, Italy, the Netherlands, France and the US.¹⁴Asbestos has to some extent been replaced by man‐made vitreous fibres (MMVF) in the insulation and construction industry. Therefore, the carcinogenic role of MMVF in humans has been widely studied in recent years.^15,16,17 In 2002 glass wool, rock wool and slag wool were categorised by the International Agency for Research on Cancer (IARC) in Group 3 (unclassifiable as carcinogens) and ceramic fibres were classified in Group 2B (possible human carcinogens) following evidence in experimental animals.¹⁸Both community‐based and industry‐based studies can contribute to our understanding of occupational carcinogenesis, but both have limitations. Valid and precise exposure information is seldom available in community‐based studies while industry‐based studies frequently cannot take into account individual smoking patterns and complete work histories of the subjects. In addition, the exposure assessment in industry‐based studies is often based on job titles and employment time only, which limits the possibility to control for confounders.^19,20,21The current study provides an opportunity to overcome the above mentioned shortcomings. By analysing data from a large, multicentre lung cancer case‐control study in Europe, with extensive estimations of past occupational exposures and lifestyle characteristics, we aim to elucidate the extent to which lung cancer burden in men in this region is driven by asbestos and man‐made vitreous fibres while controlling for potential confounders.     

Occupational risk factors of lung cancer in a French case-control study

A case-control study of 1625 histologically confirmed cases of lung cancer and 3091 controls matched for sex, age, hospital admission, and interviewer was conducted in France between 1976 and 1980. The results presented concern the effects of different occupations on the occurrence of lung cancer among 1334 male cases and 2409 matched controls. Occupations were coded blindly according to the International Standard Classification of Occupations. An excess risk of lung cancer was observed for the following occupations after adjustment for cigarette exposure: farmers (RR = 1.24, p less than 0.06), miners and quarrymen (RR = 2.14, p less than 0.02), plumbers and pipe fitters (RR = 1.80, p less than 0.04), motor vehicle drivers (RR = 1.42, p less than 0.01).     

Occupational risk factors of lung cancer: a hospital based case-control study

OBJECTIVES: To investigate the relation between lung cancer and exposure to occupational carcinogens in a highly industrialised region in western Europe. METHODS: In a case-control study 478 cases and 536 controls, recruited from 10 hospitals in the Antwerp region, were interviewed. Cases were male patients with histologically confirmed lung cancer; controls were male patients without cancer or primary lung diseases. Data were collected by questionnaires to obtain information on occupations, exposures, and smoking history. Job titles were coded with the Office of Populations, Censuses and Surveys industrial classification. Exposure was assessed by self report and by job-task exposure matrix. Exposure odds ratios were calculated with logistic regression analysis adjusted for age, smoking history, and marital and socio-economic status. RESULTS: A job history in the categories manufacturing of transport equipment other than automobiles (for example, shipyard workers), transport support services (for example, dockers), and manufacturing of metal goods (for example, welders) was significantly associated with lung cancer (odds ratios (ORs) 2.3, 1.6, and 1.6 respectively). These associations were independent of smoking, education, civil, and economic status. Self reported exposure to potential carcinogens did not show significant associations with lung cancer, probably due to nondifferential misclassification. When assessed by job-task exposure matrix, exposure to molybdenum, mineral oils, and chromium were significantly associated with lung cancer. A strong association existed between smoking and lung cancer: OR of ex- smokers 4.2, OR of current smokers 14.5 v non-smokers. However, smoking did not confound the relation between occupational exposure and lung cancer. CONCLUSIONS: The study has shown a significant excess risk of lung cancer among workers in manufacturing of metal goods, manufacturing of transport equipment (other than automobiles), and transport support services. Assessment of exposure to specific carcinogens resulted in significant associations of chromium, mineral oils, and molybdenum with lung cancer. This study is, to our knowledge, the first study reporting a significant association between occupational exposure to molybdenum and lung cancer.       

Occupational sun exposure and mycosis fungoides: a European multicenter case-control study

OBJECTIVE: We sought to study the association between occupational sun exposure and mycosis fungoides (MF), a peripheral T-cell lymphoma. SUBJECTS AND METHODS: A European multicenter case-control study including seven rare cases (one being MF) was conducted between 1995 and 1997. From the 118 accepted cases, 104 were interviewed, of which 76 were definite cases. Population controls were selected randomly from the regions of case ascertainment. Information based on occupational experiences was coded according to industry types. A job exposure matrix was created according to the expected exposure to sunlight. RESULTS: Once exposures to aromatic halogenated hydrocarbons were eliminated (odds ratio = 2.3; 95% confidence interval = 0.9-6.2), a high MF risk was associated with exposures to solar radiation. CONCLUSION: It would appear that workers exposed to sunlight have a higher risk of MF. However, this factor is not the only one involved.     

Occupational exposure to lead compounds and risk of cancer among men: a population-based case-control study

The International Agency for Research on Cancer recently classified inorganic lead as a probable carcinogen, while organic lead remained unclassifiable. Uncertainty persists because of limited epidemiologic evidence. The authors addressed the relation between occupational exposure to lead and the risk of 11 types of cancer among men in a case-control study conducted in Montreal, Quebec, Canada, in the 1980s. Incident cases (n = 3,730) and general population controls (n = 533) were interviewed to elicit information on job history and potential confounders. Expert chemists translated each job into a list of substances to which the subject had potentially been exposed. Exposure to lead was classified into three categories: organic lead (3% of subjects ever exposed), inorganic lead (17%), and lead in gasoline emissions (39%). Odds ratios and 95% confidence intervals were estimated by logistic regression using two control groups: general population controls and cancer controls. Stomach cancer was associated with organic lead when the authors used population controls (odds ratio (OR) = 3.0, 95% confidence interval (CI): 1.2, 7.3) and cancer controls (OR = 2.0, 95% CI: 1.1, 3.8) and with substantial exposure to lead in gasoline emissions when they used cancer controls (OR = 2.9, 95% CI: 1.4, 5.9). There was no association with inorganic lead and little evidence for associations with other cancer types.     

Occupational risk factors of lung cancer in a French case-control study.

A case-control study of 1625 histologically confirmed cases of lung cancer and 3091 controls matched for sex, age, hospital admission, and interviewer was conducted in France between 1976 and 1980. The results presented concern the effects of different occupations on the occurrence of lung cancer among 1334 male cases and 2409 matched controls. Occupations were coded blindly according to the International Standard Classification of Occupations. An excess risk of lung cancer was observed for the following occupations after adjustment for cigarette exposure: farmers (RR = 1.24, p less than 0.06), miners and quarrymen (RR = 2.14, p less than 0.02), plumbers and pipe fitters (RR = 1.80, p less than 0.04), motor vehicle drivers (RR = 1.42, p less than 0.01).     

Occupational exposure and lung cancer risk: a population-based case-referent study in Sweden

This case-referent study investigated the lung cancer risk from occupational exposure to diesel exhaust, mixed motor exhaust, other combustion products, asbestos, metals, oil mist, and welding fumes. All cases of lung cancer in males aged 40-75 years among stable residents of Stockholm County, Sweden, were identified from 1985 to 1990. Referents were selected as a stratified (age, inclusion year) random sample. Information on lifetime occupational history, residency, and tobacco smoking was obtained from the study subjects or from next of kin. Response rates of 87% and 85% resulted in 1,042 cases and 2,364 referents, respectively. Occupational exposures were assessed by an occupational hygienist who coded the intensity and probability of each exposure. Risk estimates were adjusted for tobacco smoking, other occupational exposures, residential radon, and environmental exposure to traffic-related air pollution. For the highest quartile of cumulative exposure versus no exposure, the relative risk was 1.63 (95% confidence interval (CI): 1.14, 2.33) for diesel exhaust, 1.60 (95% CI: 1.09, 2.34) for combustion products, and 1.68 (95% CI: 1.15, 2.46) for asbestos. Dose-response analyses indicated an increase in lung cancer risk of 14% per fiber-year/ml for asbestos exposure. No increased risk was found for the other exposure factors. An overall attributable proportion of 9.5% (95% CI: 5.5, 13.9) was estimated for lung cancer related to diesel exhaust, other combustion products, and asbestos.     

Occupational risk factors for mycosis fungoides: a European multicenter case-control study

Mycosis fungoides (MF) is a rare disease with an unknown etiology. Its distribution suggests that occupational exposures may play a role. In the present study, we searched for occupational factors associated with MF. A European multicenter case-control study on seven rare cancers, including MF, was conducted from 1995 to 1997. Patients between 35 and 69 years of age diagnosed with MF (n = 134) were identified and their diagnoses were checked by a reference pathologist who classified 83 cases as definitive, 35 cases as possible, and 16 cases as not histologically verified. Of the 118 histologically verified cases, 104 were interviewed, of which 76 were definitive cases. As controls, we selected population controls and colon cancer controls to serve all seven case groups. Altogether, 833 colon cancer controls and 2071 population controls were interviewed. The response rate was 91.5% for cases (76 of the 83 definitive cases), and 66.6% for controls. A high risk of MF for men was observed in the industries of other non-metallic mineral products (Odds Ratio [OR] 5.3, 95% confidence interval [CI] = 1.7-16.2) and of wholesale trade (OR 3.6, 95% CI = 1.3-10.5). A high risk was found for female employees in the sector of pulp paper manufacture (OR 14.4, 95% CI = 2.2-95.1). The male occupations with the highest risks were glass formers, potters, and ceramics workers (OR 17.9, 95% CI = 5.4-59.4) and technical salesmen (OR 8.6, 95% CI = 2.4-30.8). For women, the occupations associated with the highest risks were government executives (OR 4.8, 95% CI = 1.0-22.6) and railway and road vehicles loaders (OR 3.9, 95% CI = 1.0-14.0). The results suggest that some occupational factors are associated with MF. Working as glass formers, pottery, and ceramics workers carried the highest risk, and these findings deserve further attention and replication. Females working in the paper and pulp industries may also be exposed to carcinogens of relevance to MF.     

Lung cancer and occupation in nonsmokers: a multicenter case-control study in Europe

BACKGROUND: Tobacco smoking is the main cause for lung cancer worldwide, making it difficult to examine the carcinogenic role of other risk factors because of possible confounding by smoking. Therefore, the present study aimed to investigate the association between lung cancer and occupation independent of smoking. METHODS: A case-control study of lung cancer was carried out between March 1998 and January 2002 in 16 centers from 7 European countries, including 223 never-smoking cases and 1039 controls. Information on lifestyle and occupation was obtained through detailed questionnaires. Job and industries were classified as entailing exposure to known or suspected carcinogens; in addition, expert assessment provided exposure estimates to specific agents. RESULTS: The odds ratio of lung cancer among women employed for more than 12 years in suspected high-risk occupations was 1.75 (95% confidence interval = 0.63-4.85). A comparable increase in risk was not detected for employment in established high-risk occupations or among men. Increased risk of lung cancer was suggested among individuals exposed to nonferrous metal dust and fumes, crystalline silica, and organic solvents. CONCLUSION: Occupations were found to play a limited role in lung cancer risk among never-smokers. Jobs entailing exposure to suspected lung carcinogens should receive priority in future studies among women. Nonferrous metal dust and fumes and silica may exert a carcinogenic effect independently from smoking.     

Occupational lung cancer risk for men in Germany: results from a pooled case-control study

Occupational exposures such as crystalline silica, diesel engine exhaust, polycyclic aromatic hydrocarbons, and man-made mineral fibers are strongly suspected to increase lung cancer risk. Two case-control studies in Germany conducted between 1988 and 1996 were pooled for a joint analysis. A total of 3,498 male cases and 3,541 male population controls, frequency matched for age and region, were included in the study. The lifelong history of all jobs and industries was coded and occupational exposures were evaluated by expert rating. Odds ratios, crude and adjusted for smoking and asbestos exposure, were calculated by conditional logistic regression. Job-related evaluation showed a statistically significant increased odds ratio adjusted for smoking among farmers; forestry workers, fishermen, and livestock workers; miners and quarrymen; chemical processors; cabinet makers and related wood workers; metal producers and processors; bricklayers and carpenters; road construction workers, pipelayers and well diggers; plasterers, insulators, and upholsterers; painters and lacquerers; stationary engine and heavy equipment operators; transport workers and freight handlers; and service workers. With regard to specific occupational exposures, elevated odds ratios (OR) (95% confidence intervals (CI)) for lung cancer risk adjusted for smoking and asbestos exposure were observed for man-made mineral fibers (OR = 1.48, 95% CI 1.17, 1.88); crystalline silica (OR = 1.41, 95% CI 1.22, 1.62); diesel engine exhaust (OR = 1.43, 95% CI 1.23, 1.67); and polycyclic aromatic hydrocarbons (OR = 1.53, 95% CI 1.14, 2.04). The risk of asbestos exposure, adjusted for smoking was also increased (OR = 1.41, 95% CI 1.24, 1.60).     

Residential randon exposure and lung cancer risk in Misasa, Japan: a case-control study

In order to investigate an association between residential radon exposure and risk of lung cancer, a case-control study was conducted in Misasa Town, Tottori Prefecture, Japan. The case series consisted of 28 people who had died of lung cancer in the years 1976-96 and 36 controls chosen randomly from the residents in 1976, matched by sex and year of birth. Individual residential radon concentrations were measured for 1 year with alpha track detectors. The average radon concentration was 46 Bq/m3 for cases and 51 Bq/m3 for controls. Compared to the level of 24 or less Bq/m3, the adjusted odds ratios of lung cancer associated with radon levels of 25-49, 50-99 and 100 or more Bq/m3, were 1.13 (95% confidence interval; 0.29-4.40), 1.23 (0.16-9.39) and 0.25 (0.03-2.33), respectively. None of the estimates showed statistical significance, due to small sample size. When the subjects were limited to only include residents of more than 30 years, the estimates did not change substantially. This study did not find that the risk pattern of lung cancer, possibly associated with residential radon exposure, in Misasa Town differed from patterns observed in other countries.     

A case-control study of lung cancer in relation to silica exposure and silicosis in a rural area in Japan

PURPOSE: In southeast Okayama Prefecture, Japan, there have been reports of a high prevalence of silicosis among refractory brick production workers. Recently, a high mortality rate of lung cancer among the local residents has been observed. Therefore, a population based case-control study was conducted concerning the relationship between silica, silicosis, and lung cancer using multiple cancer controls. METHODS: Cases and controls were restricted to male subjects and information was obtained from death certificates from 1986 to 1993 in the area. Three categories of deceased control groups were selected: a series of deaths from liver cancer, colon cancer, and cancers of other organs, which was assumed not to be related to silica exposure. Age and smoking habits were adjusted by stratified analysis using the Mantel-Haenszel odds ratio estimates. Unconditional logistic regression analysis was also conducted to control potential confounding factors; such as age and smoking habits. RESULTS: The age-, smoking-adjusted odds ratios were 1.94 (0.94-4.43) for the colon cancer control group, 2.13 (1.19-3.85) for the other cancer control group related to silica exposure, and 2.94 (1.30-8.90) and 2.69 (1.43-5.37) related to silicosis, respectively. The direct weighted average using the estimates for colon and the other cancer controls was 2.06 (1.29-3.29) for silica exposure, and 2.77 (1.60-4.77) for silicosis. Histological or cytological types of lung cancer cases were obtained from 64.1% of the subjects (118/184). As for the histologic type of lung cancer, small cell carcinoma was higher among those who had been silica-exposed workers than the unexposed lung cancer cases and the data from the general Japanese population. On chest x-ray findings, elevated lung cancer mortality compared with cancers other than lung cancer was demonstrated among patients without large opacities. CONCLUSIONS: Silica exposure increased the lung cancer mortality in the area. A high lung cancer mortality rate in the area could be explained by silica exposure and silicosis prevalence in this area.     

Radon progeny exposure and lung cancer risk in New Mexico U miners: a case-control study

A case-control study was conducted to describe lung cancer risk in a cohort of New Mexico underground U miners. The subjects included 65 cases and 230 age-matched controls, most with exposures below 3.50 J h m-3 (1000 WLM). The risk for lung cancer was increased for all cumulative exposures to Rn progeny of 0.35 J h m-3 (100 WLM) or greater. The odds ratios were unchanged with control for cigarette smoking. With exclusion of subjects with exposures above 3.50 J h m-3 (1000 WLM), the estimated excess relative risk was 0.3% per mJ h m-3 (1.1% per WLM). The risk was greater for younger subjects and the data were consistent with a multiplicative interaction between cigarette smoking and exposure to Rn progeny.     

Silica exposure and lung cancer in ceramic workers: a case-control study

The results are presented from a case-control study, concerning the possible relation between silica exposure in the Dutch fine ceramic industry and lung cancer. For this purpose 381 male, age-matched pairs of primary lung cancer cases and controls were selected from the pathology department of the University Hospital in the region, where two large ceramic companies are located. Information about employment in the ceramic industry was obtained from the personnel and financial administration departments of the two companies. On the basis of job titles a panel of occupational hygiene experts reached consensus about the qualitative exposures of each individual worker. Twenty one per cent of the cases were employed in the ceramic industry, compared with 19% of the controls (odds ratio 1.11; 95% Cl: 0.77-1.61). Although the average employment period of cases and their relative silica exposure surpassed those of controls, odds ratios for long duration of employment and considerable exposure to respirable silica dust did not reach statistical significance. After constructing a qualitative exposure index, based on the amount and duration of exposure, a tendency towards a positive correlation with lung cancer emerged. No relation between specific histological tumour cell types and working in the ceramic industry emerged. Although the study does not suggest a consistent cause-effect relation between silica exposure in the regional, Dutch fine ceramic industry and lung cancer, an increased risk for the high exposure group in the past can not be totally excluded.     

Indoor radon exposure and lung cancer risk: a review of case-control studies

BACKGROUND: Radon is a radioactive gas that tends to accumulate in indoor environment. A causal relationship between lung cancer and radon exposure has been demonstrated in epidemiologic studies of miners. The objective of this paper is to present the results of case-control studies of lung cancer risk associated with indoor radon exposure. METHODS: Case-control studies published since 1990 are included in this review. This type of protocol is particularly well suited for studying the relationship between indoor radon exposure and lung cancer risk, taking into account possible confounding factors such as tobacco smoking. The characteristics and results of these studies are summarized. The limitations associated with each of these studies are also discussed. RESULTS: The results of available studies are relatively concordant and suggest a positive association between lung cancer risk and indoor radon exposure with an estimated excess relative risk of about 6 to 9% per 100Bq/m3 increase in the observed time-weighted average radon concentration. The order of magnitude of this estimation agrees with extrapolations from miners but some studies may suffer from inadequate statistical power. CONCLUSION: At present, efforts are underway to pool together the data from the existing studies of indoor radon. This pooling analysis with thousands of cases and controls will provide a more precise estimate of the lung cancer risk from indoor radon exposure and explore the effect of modifying factors, such as smoking.