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.     

Dietary risk factors for kidney cancer in Eastern and Central Europe

The authors examined the role of diet in the high-risk population of Central Europe among 1,065 incident kidney cancer cases and 1,509 controls in Russia, Romania, Poland, and the Czech Republic. They observed an increased association with kidney cancer for consumption of milk (odds ratio (OR) = 1.46, 95% confidence interval (CI): 1.15, 1.84) and yogurt (OR = 1.34, 95% CI: 1.07, 1.67), as well as all meat (OR = 1.27, 95% CI: 1.06, 1.51 compared with the lowest tertile). High consumption of all vegetables (OR = 0.64, 95% CI: 0.51, 0.80) and cruciferous vegetables (OR = 0.68, 95% CI: 0.55, 0.84) was inversely associated with kidney cancer. In addition, high consumption of preserved vegetables increased the risk of kidney cancer (OR = 1.66, 95% CI: 1.24, 2.21). Alcohol consumption did not appear to be associated with kidney cancer. This 1999-2003 study provides further evidence that diet may play a role in the development of kidney cancer, with a particularly strong protective association for high vegetable intake. The increased risk associated with dairy products, preserved vegetables, and red meat provides clues to the high rates of kidney cancer in this population.     

Contribution of tobacco and alcohol to the high rates of squamous cell carcinoma of the supraglottis and glottis in Central Europe

Incidence rates for laryngeal cancer in Central Europe are among the highest in the world. The authors recruited cases and controls between 2000 and 2002 for the Central and Eastern Europe Multicenter Study to investigate the role of tobacco and alcohol as causes of laryngeal cancer in this region. A total of 384 incident squamous cell cases were included, comprising 254 glottic and 108 supraglottic cancers. Hospital controls were chosen from within the same catchment area, from diseases unrelated to tobacco or alcohol (n = 918). Significant dose-response trends for frequency and duration of tobacco use were observed for both supraglottic and glottic cancers, with potentially a more important effect for supraglottic cancer. Quitting smoking was protective against laryngeal cancers after 5 years. Any increases in risk for alcohol drinking were generally moderate and nonsignificant. A greater than multiplicative interaction was observed between tobacco and alcohol on the risk of laryngeal cancer (p = 0.04). Approximately 87% of laryngeal cancer cases in Central Europe are attributable to tobacco use, of which 75% and 12% are due to current and past smoking, respectively. Approximately 39% are attributable to the interaction between alcohol and tobacco. Preventive efforts to encourage current smokers to quit are likely to be the most effective way to reduce the incidence of laryngeal cancer in this region.     

Glutathione S-transferase M1 and P1 metabolic polymorphism and lung cancer predisposition

Individual susceptibility to different environmental agents is expected to be associated with alterations in metabolism of xenobiotics. Thus, genetic polymorphism of glutathione S-transferase (GST) can be recognized as a potential risk modifier in lung cancer development. The distribution of GSTM1 and GSTP1 genotypes was studied in a group of 138 diagnosed lung cancer patients and in 165 controls living in central Poland and RFLP-PCR technique was applied. The frequency of GSTM1 null genotype and GSTP1 Val single and duplicated alleles was similar among patients and controls. GSTM1 homozygous deletion was most prevalent in small-cell carcinoma groups (adjusted odds ratio (OR): 2.32, 95% confidence interval (CI): 0.98-5.52). In patients and controls, GSTM1A genotype was most frequent (34.1% vs. 37.0%). The estimated lung cancer risk for GSTM1 null, GSTP1 Ile/Val and GSTP1 Val/Val combined genotype was 1.44 (95% CI: 0.73-2.83), suggesting the absence of modifying effect of defective GSTM1 and GSTP1 alleles on lung cancer predisposition.     

Tobacco smoking, body mass index, hypertension, and kidney cancer risk in central and eastern Europe

In a case–control study of kidney cancer in four central European countries, with 1097 incident cases and 1476 controls, we found an increased risk for self-reported hypertension and for obesity. Additional unknown risk factors are likely to be responsible for the high rates of kidney cancer in this region.     

Asbestos in Poland: Occupational health problems

The presentation addresses current problems of health risk and health effects associated with exposure to asbestos, including data on historical exposure and on currently valid occupational exposure limits. The quantity and types of the raw material used for the production of various asbestos products have also been discussed in relation to the particular types of asbestos-induced occupational diseases. The authors describe the medical care system for former asbestos workers and those currently exposed during removal of asbestos-containing products. The national system for medical certification of occupational asbestos-related diseases and the compensation procedure have been outlined as well. According to the parliamentary Act of 1997, importing, manufacture and sale of asbestos and asbestos-containing materials are prohibited in Poland. Thus, the assessment of asbestos exposure and the monitoring of health conditions of workers at asbestos-processing plants have become irrelevant. However, the delayed health effects attributable to past exposure continue to be the matter of concern for public health. Likewise, the environmental pollution from asbestos waste landfills in the vicinity of asbestos-processing plants (where high levels of asbestos fibre in ambient air have been recorded) will continue to be a serious public health problem. Presently, two programmes aimed at minimising the adverse effects of asbestos on population health are underway. One of them is the governmental programme for "Elimination of asbestos and asbestos-containing products used in Poland, 2002-2032". The programme was updated in 2009 to cover the workers contracted to perform demolition works and provide protective covers to asbestos waste landfills. This will be the exposed group who need prophylactic health care. The other is a programme of prophylactic examinations for former asbestos workers and is referred to as the AMIANTUS programme. Both programmes have been briefly described.     

Sequence variants in cell cycle control pathway, X-ray exposure, and lung cancer risk: a multicenter case-control study in Central Europe

Exposure to ionizing radiation (IR) results in various types of DNA damage and is a suspected cause of lung cancer. An essential cellular machinery against DNA damage is cell cycle control, which is regulated by several genes, including TP53, CCND1, and CDKN2A. Therefore, we hypothesized that the genetic variants in these three genes influence the predisposition of lung cancer (i.e., CCND1 G870A, CDKN2A Ala(148)Thr, TP53 Arg(72)Pro, and 16-bp repeat in intron 3) and that the effect of X-ray on lung cancer risk can be modified by the presence of these genetic variations. The study was conducted in 15 centers in 6 countries of Central Europe between 1998 and 2002. A total of 2,238 cases and 2,289 controls were recruited and provided DNA samples. Cases with positive family history were analyzed separately. The joint effect of X-ray and previous risk genotypes was assessed, and modification by sequence variants on X-ray dose-response relationship with lung cancer risk was evaluated. We found an overall effect of TP53 intron 3 16-bp repeats [odds ratio (OR), 1.99; 95% confidence interval (95% CI), 1.27-3.13], which was stronger among cases with family history of lung cancer (OR, 2.98; 95% CI, 1.29-6.87). In addition, our results suggested an interaction that was greater than multiplicativity between TP53 intron 3 16-bp repeats and multiple X-ray exposures (interaction OR, 5.69; 95% CI, 1.33-24.3). We did not observe a main effect of CCND1 G870A polymorphism; however, the dose-response relationship between lung cancer risk and X-ray exposures was modified by CCND1 genotype with no risk from X-ray exposures among subjects who carried G/G genotype, intermediate risk [trend OR for X-ray, 1.16; 95% CI, 1.05-1.27) among subjects with G/A genotype, and highest risk [trend OR for X-ray, 1.29; 95% CI, 1.12-1.49) among subjects with A/A genotype. Sequence variants in cell cycle control pathway may increase the risk of lung cancer and modify the risk conferred by multiple X-ray exposures. However, a definite conclusion can only be drawn on replication by different studies among individuals who are highly exposed to IR.     

Methodology for lognormal modelling of malignant pleural mesothelioma survival time distributions: a study of 5580 case histories from Europe and USA

A truncated left-censored and right-censored lognormal model has been validated for representing pleural mesothelioma survival times in the range 5-200 weeks for data subsets grouped by age for males, 40-49, 50-59, 60-69, 70-79 and 80+ years and for all ages combined for females. The cases available for study were from Europe and USA and totalled 5580. This is larger than any other pleural mesothelioma cohort accrued for study. The methodology describes the computation of reference baseline probabilities, 5-200 weeks, which can be used in clinical trials to assess results of future promising treatment methods. This study is an extension of previous lognormal modelling by Mould et al (2002 Phys. Med. Biol. 47 3893-924) to predict long-term cancer survival from short-term data where the proportion cured is denoted by C and the uncured proportion, which can be represented by a lognormal, by (1 - C). Pleural mesothelioma is a special case when C = 0.     

Cancer mortality in rubber tire workers in Poland

The study aimed at assessing cancer risk in a cohort of workers employed in the rubber tire production. The cohort consisted of 17,747 workers (11,660 men and 6087 women) employed in a rubber tire plant for at least three months during the years 1950-1995. The cohort follow-up was completed on December 31, 1995. Deaths by causes were analyzed using standardized mortality ratio (SMR) calculated by the person-years method. The mortality pattern of the general population of Poland was used as the reference. The study indicated significantly lower total mortality in the cohort (men: SMR = 72; women: SMR = 62) as compared to the general population, which is an example of a well known "healthy worker effect". The number of deaths from malignant neoplasms was also lower than expected (men: SMR = 67; women: SMR = 64). Only in a very small sub-cohort of men involved in dosing and mixing of raw material for the production of rubber, an excess of total mortality (SMR = 104) and from all cancers (SMR = 115) was found. Mortality from all neoplasms was enhanced (SMR = 108) in the sub-cohort of women employed in the technical service work area. When analyzing individual cancer sites in men of the whole cohort or sub-cohorts, the observed number of deaths from cancers of the lip, tongue, pharynx, stomach, gallbladder, pancreas, peritoneum, articular cartilage, connective tissue, skin, testis, prostate, bladder, kidney, brain, as well as from Hodgkin's disease, multiple myeloma and leukemia was larger than the expected number. Among women the excess mortality was due to cancers of the large myeloma and leukemia. The SMR calculated for these sites were statistically insignificant. The cohort under study was "young" and thus relatively small numbers of deaths were recorded. The excess mortality, based quite frequently on single cases of selected cancer sites, cannot be regarded as a basis for final conclusions. Nevertheless, the fact that these observations are in agreement with the findings of other authors who carried out studies in the rubber industry of other countries justifies the need to follow-up this cohort in the future.