Predictors of lung cancer among former asbestos-exposed workers

ObjectivesDespite extensive literature concerning the risk of lung cancer incidence among asbestos workers there is still lack of data specifying the association between the level of exposure and the frequency of cancer occurrence. The aim of the analysis was to assess the influence of smoking and selected factors related to occupational exposure on the risk of the incidence of lung cancer among the workers who were exposed to asbestos dust in the past.Material and methodsThe assessment was performed based on the case-control studies carried out within a cohort including 7,374 former workers of asbestos processing plants, examined over the years 2000–2013. Analysis of the material was based on the calculation of the odds ratio (OR) using conditional logistic regression modeling, adjusted for cigarette smoking, cumulative exposure, branch and time since last exposure.ResultsDuring the survey period there were 165 cases of lung cancer. Among the individuals who smoked, the relative risk of lung cancer incidence was twice as high in the persons smoking more than 20 pack-years (OR = 2.23; 95%CI: 1.45–3.46) than it was in the case of the non-smokers. Analysis revealed that the risk of lung cancer in the group with the highest exposure was two times higher in comparison with the low cumulative asbestos exposure (OR = 1.99; 95%CI: 1.22–3.25). The risk continued to increase until 30 years after cessation of asbestos exposure and started to decline many years after the last exposure. Influence of the mentioned above characteristics is particularly visible for tumors located in the lower parts of the lungs.ConclusionOur findings confirm the strong evidence that the lung cancer risk is associated with asbestos exposure and it increases along with the increasing exposure. A strategy of smoking cessation among the individuals exposed to asbestos dust would potentially have health promoting effects.     

Occupational asbestos exposure and risk of esophageal,gastric and colorectal cancer in the prospective Netherlands Cohort Study

The evidence for an association between occupational asbestos exposure and esophageal, gastric and colorectal cancer is limited. We studied this association specifically addressing risk differences between relatively low and high exposure, risk associated with cancer subtypes, the influence of potential confounders and the interaction between asbestos and smoking in relation to cancer risk. Using the Netherlands Cohort Study (n = 58,279 men, aged 55–69 years at baseline), asbestos exposure was estimated by linkage to a job‐exposure matrix. After 17.3 years of follow‐up, 187 esophageal, 486 gastric and 1,724 colorectal cancer cases were available for analysis. The models adjusted for age and family history of cancer showed that mainly (prolonged) exposure to high levels of asbestos was statistically significantly associated with risk of esophageal adenocarcinoma (EAC), total and distal colon cancer and rectal cancer. For overall gastric cancer and gastric non‐cardia adenocarcinoma (GNCA), also exposure to lower levels of asbestos was associated. Additional adjustment for lifestyle confounders, especially smoking status, yielded non‐significant associations with overall gastric cancer and GNCA in the multivariable‐adjusted model, except for the prolonged highly exposed subjects (tertile 3 vs. never: HR 2.67, 95% CI: 1.11–6.44 and HR 3.35, 95% CI: 1.33–8.44, respectively). No statistically significant additive or multiplicative interaction between asbestos and smoking was observed for any of the studied cancers. This prospective population‐based study showed that (prolonged) high asbestos exposure was associated with overall gastric cancer, EAC, GNCA, total and distal colon cancer and rectal cancer.     

Evaluation of double cancers in relation to previous asbestos exposure

Ten cases of double cancers (a lung cancer and a stomach cancer) were evaluated in relation to previous asbestos exposure. Ten cases involved male more than 69 years old. Five cases had developed their two cancers simultaneously and other 5 cases had developed their lung cancer after stomach cancer surgery. The lung cancer was their main disease. Four cases had early stage stomach cancers and 5 cases with a stomach cancer had no relapse after surgery. Eight cases had occupational histories of asbestos exposure. Significantly high numbers of asbestos bodies were detected in the autopsied lung in almost all cases. According to the X-ray analysis, almost all asbestos fibers detected in the lung were chrysotile. Additionally, the Brinkman Index (B.I.) of these 10 cases ranged between 700 and 2,000. The combination of asbestos exposure and smoking is thought to be an important factor in the development of such double cancers.     

Relationship of cigarette smoking and radiation exposure to cancer mortality in Hiroshima and Nagasaki

Cancer mortality among 40,498 Hiroshima and Nagasaki residents was examined in relation to cigarette smoking habits and estimated atomic bomb radiation exposure level. Relative risk (RR) models that are either multiplicative or additive in the two exposures were emphasized. Most analyses were directed toward all nonhematologic (ANH) cancer, stomach cancer, lung cancer, or digestive tract cancer other than stomach cancer, for which there were, respectively, 1,725, 658, 281, and 338 deaths in the follow-up period for this study. Persons heavily exposed to both cigarette smoke and radiation were found to have significantly lower cancer mortality than multiplicative RR models would suggest for ANH cancer, stomach cancer, and digestive tract cancer other than stomach cancer. Surprisingly, the RR function appeared not only to be submultiplicative for some of these cancer site categories but also may be subadditive. The lung cancer RR function could not be distinguished from either a multiplicative or an additive form. The number of deaths was sufficient to permit some more detailed study of ANH cancer mortality: RR functions appeared to be consistent between males and females, though a paucity of heavy smoking females limits the precision of this comparison. The submultiplicative nature of the RR function mentioned above was particularly pronounced among persons who were relatively young (less than or equal to 30 yr of age) at the time of radiation exposure. The RR function for these younger subjects depends strongly on both radiation and cigarette smoke exposure levels. Even light smoking (approximately 5 cigarettes/day) for an extended period of time was associated with a large estimated RR. Implications of these findings are discussed in relation to human carcinogenesis models. As a byproduct, cancer mortality of several sites is significantly related to radiation exposure in this population, after accommodation for the possible confounding effects of cigarette smoking.     

Clinical study of asbestos‐related lung cancer in Japan with special reference to occupational history

A total of 152 patients with asbestos‐related lung cancer recognized by the criteria of Japanese compensation law for asbestos‐related diseases were examined and compared with 431 patients with non‐asbestos‐related lung cancer. Male comprised 96% of patients. Ages ranged from 50 to 91 years with a median of 72 years. Eighty‐nine percent were smokers or ex‐smokers. Almost all patients had occupational histories of asbestos exposure. The median duration of asbestos exposure was 31 years and the median latency period was 47 years. Thirty‐four percent of patients exhibited asbestosis and 81% exhibited pleural plaques by radiography. Regarding asbestos particles in the lung for 73 operated or autopsied patients, 62% had more than 5,000 particles per gram. On the other hand, 100% of non‐asbestos‐related lung cancer patients had <5000 particles per gram with a median of 554 particles. The number of asbestos bodies in the lung, male gender, absence of symptoms, smoking index, and early stage of cancer were significantly much more than those of non‐asbestos‐related lung cancer. In this study, a diagnosis of asbestos‐related lung cancer was made in 34% of patients by asbestosis, in 62% by presence of both pleural plaques and more than 10 years’ occupational asbestos exposure, and in 4% by more than 5000 asbestos particles per gram of lung tissue. Occupational histories, duration of asbestos exposure, and pleural plaques are common categories for the recognition of asbestos‐related lung cancer in Japan. (Cancer Sci 2010; 101: 1194–1198)     

Asbestos, dental X-rays, tobacco, and alcohol in the epidemiology of laryngeal cancer.

A case-control study of 47 laryngeal cancers in males of three counties of Washington State was conducted. Personal interview was used to obtain information on smoking, alcohol use, exposure to asbestos, and other substances, and x-rays of the head and neck area. Smoking and alcohol consumption were found to increase risk of laryngeal cancer independently, with a clear dose-response relationship. Neither asbestos exposure nor exposure to other substances was found to significantly increase the risk of laryngeal cancer, although the relative risk with asbestos exposure was 1.75. Lifetime history of exposure to dental x-rays on five or more occasions was associated with significantly increased risk of laryngeal cancer among heavy smokers but not among light smokers. The importance of tobacco and alcohol in the epidemiology of laryngeal cancer was re-affirmed, the importance of asbestos exposure was brought into question, and a possible relationship of laryngeal cancer with exposure to dental x-rays among heavy smokers was demonstrated.     

Passive smoking and cancer risk: the nature and uses of epidemiological evidence

The apparent effect of passive smoking on cancer risk has become an important social and political issue. For this reason alone the strength of the epidemiological evidence warrants close examination. The research published to date indicates a positive association of passive smoking with lung cancer, but there is no consistent evidence of associations with cancer at other sites. We have summarised the epidemiological evidence, and examined the major criticisms raised against these studies. These criticisms include alleged bias arising from misclassification of exposure to environmental tobacco smoke (ETS) or of personal smoking history, and from differential publication of positive findings. In their strongest form, these critiques challenge the ability of epidemiology to establish causation on any issue. We argue that epidemiology is not inherently different from other branches of science—in each of which scientific “proof” of cause and effect involves judgement based on measurement and logical inference. We also describe the application of epidemiological data to establishing proof, in courts of law, of the lung cancer risk of passive smoking.     

Aerodigestive and gastrointestinal tract cancers and exposure to crocidolite (blue asbestos): incidence and mortality among former crocidolite workers

The objective of this article was to assess the association between the incidence and mortality from aerodigestive cancers and exposure to crocidolite (blue asbestos). Our study is a cohort study of former workers of the now-defunct crocidolite mining and milling operation at Wittenoom, Western Australia, who have been followed up since 1979 and on whom asbestos exposure and smoking information was known. Standardised mortality and incidence rates were used to compare former workers with the Western Australian male population. Cases were matched with up to 10 randomly assigned controls, and conditional logistic regression was used to examine the relationship between asbestos exposure, smoking status and cancer incidence. There were 129 incident cases from all cancers of interest and 57 deaths. Former workers had a significantly higher risk of mortality from upper aerodigestive cancers than the Western Australian male population. The incidence of upper and lower aerodigestive cancers was higher in the Wittenoom cohort but not significantly so. Cumulative exposure to asbestos did not appear to be associated with the incidence of stomach cancer, colorectal cancer or upper aerodigestive cancers. Smoking status was strongly associated with the incidence of upper aerodigestive cancers, with current smokers experiencing the greatest risk. Our study with longer and more complete follow-up, smoking information and a stronger study design does not show an association between cumulative asbestos exposure and stomach cancer or other gastrointestinal cancers. The excess mortality from upper aerodigestive cancers seen in this cohort of former asbestos workers compared to the Western Australian male population does not appear to be associated with exposure to crocidolite.     

Incidence and etiology of lung cancer in the Pacific Basin

Incidence of lung cancer in the Pacific Basin was either compiled from published reports or computed by the authors. The results showed a great variation in age-standardized annual incidence rates of lung cancer among 10 countries and 17 areas in the Pacific Basin where tumor registry statistics are available. For males the incidence rates ranged from 10 to over 70 and for females from less than 5 to over 30/100,000 population. The reason(s) for the great variation is unclear. Ionizing radiation, carcinogenic chemical substances (e.g., chromium, arsenic compounds, asbestos, etc.), or air pollution are unlikely to be responsible. Because cigarette smoking is known to be a major cause of lung cancer, the authors have suggested that surveys on cigarette smoking be conducted among various populations in the Pacific Basin so that etiologic significance of cigarette smoking for the noted variation can be assessed. In Hawaii such a survey is underway, and a preliminary analysis was made to examine the association between lung cancer and cigarette smoking among five races.     

p53 protein, EGF receptor, and anti-p53 antibodies in serum from patients with occupationally derived lung cancer.

The oncogene product epidermal growth factor receptor (EGF-R), the tumour suppressor gene product p53 and anti-p53 antibodies are detectable in the serum of certain cancer patients. Increased levels of some of these products were reported in lung cancer patients after occupational asbestos exposure and after exposure to polycyclic aromatic hydrocarbons or vinylchloride. In the first step, this study investigated the possible diagnostic value of serum EGF-R, p53-protein and anti-p53 antibodies, measured by an enzyme-linked immunosorbent assay, in lung tumour patients. In addition to being investigated on a molecular epidemiological basis, these parameters were examined as biomarkers of carcinogenesis, especially with regard to asbestos incorporation effects or of radon-induced lung cancers. Also, a possible effect of cigarette smoking and age dependence were studied. A total of 116 male patients with lung or pleural tumours were examined. The histological classification was four small-cell cancers, six large-cell cancers, 32 adenocarcinomas, 47 squamous carcinomas, 12 mixed lung carcinomas, five diffuse malignant mesotheliomas and ten lung metastasis of extrapulmonary tumours. Twenty-two lung cancers and all mesotheliomas were related to asbestos, 22 lung cancers were related to ionizing radiation and 61 patients had cigarette smoke-related lung cancer. Besides these patients 50 male patients with non-malignant lung or pleural diseases were included; of the latter eight subjects suffered from asbestosis. Controls were 129 male subjects without any lung disease. No significantly elevated or decreased serum values for p53 protein, EGF-R, or anti-p53 antibodies as a function of histological tumour type, age, or degree and type of exposure (asbestos, smoking, ionizing radiation) could be found. The utility of p53-protein, EGF-R and anti-p53 antibodies as routine biomarkers for screening occupationally derived lung cancers is limited.     

Cigarette smoking and lung cancer: reanalysis of the British doctors' data

Attention has focused recently on the recessive oncogenesis model, according to which inactivation of both alleles of specific genes leads to cancer. A mathematical formulation of this model was fitted to the lung cancer incidence data from a cohort study among British doctors. The model described the data well. One implication is that age influences lung cancer risk among smokers independently of duration of smoking. A study of dose-response within the framework of the model shows that the data are consistent with various interpretations regarding the relative importance of daily level of smoking and duration of smoking in determining lung cancer risk.     

Lung cancer in Brazil

Lung cancer is the second leading cause of death in Brazil, after exclusion of external causes. Registries in the country are not reliable because of under-registration and limited coverage. Incidence rates for Brazil are less then half those for selected areas with good registries. Crude and adjusted incidence and mortality rates for lung cancer are rising, particularly among women. The main reason is the acceleration in tobacco consumption and the spread of smoking among women. At present, approximately 40% of men and 25% of women, 15 years of age or older, are current smokers. In the state of Rio Grande do Sul, where registries are reliable, incidence and mortality for males are similar to US data and the figures for women are rapidly approaching those for men. Occupations associated with risks of exposure to respiratory carcinogens show a rise in the incidence of lung cancer in the industrialized area of S?o Paulo. The main occupational risk in Brazil is exposure to mineral dusts, silica, or asbestos. Although about 15 million Brazilians are exposed to pesticides, agricultural workers were not a risk group for lung cancer in a case-control study. Pesticides containing arsenic and dichlorodiphenyltrichloroethane (DDT) are banned. In recent years, a trend towards a decrease in male smoking has been noted, but there is still a high tobacco exposure burden in both males and females, with a forecast of a further increase in rates of lung cancer incidence and deaths. Control of respiratory carcinogens at work continues to be a problem, particularly in the present scenario of economic and political pressures on Brazil and other developing nations. Semin Oncol 28:143-152.     

Cancer et environnement: le cas de l’amiante

Asbestos has been used extensively in industrialised countries for more than a century, causing ongoing increases in mortality from mesothelioma. Despite its regulation and ban in France in 1997, and because of the 30-year cancer latency period after exposure to it, mortality from mesothelioma will continue to increase in the country for several decades, peaking between 2020 and 2030. The risk of mesothelioma from asbestos exposure is dose dependent and higher for amphiboles. For lung cancer, the risk increases linearly with cumulative exposure, regardless of the type of asbestos; this risk is similar in the presence or absence of pleural plaques. Smoking acts with asbestos to greatly increase the risk of lung cancer, but the effects of asbestos and smoking are independent. Regarding low-level exposure, an excess of mesothelioma and lung cancer has been observed in the vicinity of mines, asbestos manufacturers and natural geologic sites (para-occupational, domestic and environmental exposure); we have been unable to demonstrate safe levels of asbestos exposure.     

Cancer mortality among Chinese chrysotile asbestos textile workers

To determine mortality associated with exposure to chrysotile asbestos, a cohort of asbestos workers from an asbestos textile factory in China was followed prospectively from 1972 to 2008. A total 577 workers were successfully followed, achieving a follow-up rate of 98.5% over 37 years. Employment data and smoking information were obtained from factory and individual workers. Vital status was ascertained from factory personnel records and the municipal death registry. Workers were categorized into high, medium and low exposure groups in terms of their job titles and workshops. Follow-up generated 17,508 person-years, with 259 deaths from all causes, 96 all cancers and 53 lung cancers and 2 mesotheliomas. The highest cancer mortality was observed in the high exposure group, with 1.5-fold age-adjusted mortality from all cancers and 2-fold from lung cancer compared to the low exposure group. Age and smoking adjusted hazard ratio in the high exposure group was 2.99 (95%CI, 1.30, 6.91) for lung cancer and 2.04 (1.12, 3.71) for all cancers. Both smokers and nonsmokers at the high exposure level had a high death risk of lung cancer, with a clearer exposure-response trend seen in smokers. This study confirmed increased mortality from lung cancer and all cancers in asbestos workers, and the cancer mortality was associated with exposure level.     

A case-control study on occupational lung cancer risks in an industrialized city of Japan.

A hospital-based case-control study was conducted to evaluate occupational risks of lung cancer in an industrialized city of Japan. The lung cancer cases were obtained from 3 major hospitals in the city. The control group consisted of patients with a variety of diseases hospitalized in the same wards of the same hospitals as the cases. After matching on sex, 5-year age category and hospital, 144 cases and 676 controls comprised the study group. A self-administered questionnaire was used to obtain lifetime job histories and smoking status. The conditional logistic regression model was used to estimate relative risks after controlling for smoking and employment in other jobs. The workers in shipbuilding, ironworks and other plants (mostly chemical plants) showed statistically significant increases in lung cancer risk with relative risks of 6.18, 2.02, and 2.66, respectively. An increase in risk with the duration of employment was also observed in the "other plants" category. Building and road construction workers also showed increased relative risks, 1.95 and 1.79, but they were not significant. When the risk was evaluated on the exposure chemicals, the workers exposed to inorganic acids and bases had significantly increased risk. The workers exposed to asbestos, dust or organic chemicals also showed increased risk but the effects were not significant. The combined effect of smoking and employment in ironworks showed a good fit to an additive model, while that in the "other plants" category was closer to a multiplicative model.     

Lung cancer risk, occupational exposure, and the debrisoquine metabolic phenotype

The risk of lung cancer in smokers was examined based on the debrisoquine metabolic phenotype and on exposure to occupational lung carcinogens, specifically asbestos and polycyclic aromatic hydrocarbons. Extensive metabolizers of debrisoquine are at a 4-fold increased risk for lung cancer compared to poor metabolizers, after adjustment for age, sex, and smoking (pack-years), when only occupationally unexposed subjects are considered. Increased risk related to the debrisoquine metabolic phenotype was greatest for squamous and small cell histologies, and least for the adenocarcinoma subtype. Men with a history of exposure to occupational carcinogens had significantly increased risk of lung cancer (relative risk = 2.8), after adjustment for age and smoking. Considering the combined effect of the high risk extensive metabolizers debrisoquine metabolic phenotype and likely occupational exposure to asbestos, the relative excess risk for lung cancer was 18-fold. This finding is consistent with a synergism in risk between the ability to extensively metabolize debrisoquine and occupational exposure to lung carcinogens in male smokers. Debrisoquine phenotyping has potential for identifying carcinogen-exposed workers at high risk of lung cancer.     

Relation of environmental exposure to erionite fibres to risk of respiratory cancer

During the period 1979-1983, IARC, in collaboration with the Department of Chest Diseases of Hacettepe University in Ankara and the MRC Pneumoconiosis Unit in Penarth, conducted an epidemiological and environmental survey in 4 villages in central Turkey affected by a high incidence of mesothelial tumours. Recent data point to erionite, a zeolite fibre, as the most plausible etiological agent. From animal experiments, erionite appears to be the most powerful carcinogenic fibre so far known. During the study period, 17 pleural mesotheliomas and 7 lung cancer cases have been reported among the villagers. These cancer cases are analysed in relation to exposure to fibres. We assume exposure to occur from birth onwards and therefore consider duration of exposure equal to age. On this basis, the incidence of mesothelial and lung tumours is analysed in relation to age and cumulative exposure to fibres computed using the airborne fibre levels measured during the survey.     

A Case-Control Study on Occupational Lung Cancer Risks in an Industrialized City of Japan

A hospital-based case-control study was conducted to evaluate occupational risks of lung cancer in an industrialized city of Japan. The lung cancer cases were obtained from 3 major hospitals in the city. The control group consisted of patients with a variety of diseases hospitalized in the same wards of the same hospitals as the cases. After matching on sex, 5–year age category and hospital, 144 cases and 676 controls comprised the study group. A self-administered questionnaire was used to obtain lifetime job histories and smoking status. The conditional logistic regression model was used to estimate relative risks after controlling for smoking and employment in other jobs. The workers in shipbuilding, ironworks and other plants (mostly chemical plants) showed statistically significant increases in lung cancer risk with relative risks of 6.18, 2.02, and 2.66, respectively. An increase in risk with the duration of employment was also observed in the "other plants" category. Building and road construction workers also showed increased relative risks, 1.95 and 1.79, but they were not significant. When the risk was evaluated on the exposure chemicals, the workers exposed to inorganic acids and bases had significantly increased risk. The workers exposed to asbestos, dust or organic chemicals also showed increased risk but the effects were not significant. The combined effect of smoking and employment in ironworks showed a good fit to an additive model, while that in the "other plants" category was closer to a multiplicative model.     

Lack of interaction between asbestos exposure and glutathione S-transferase M1 and T1 genotypes in lung carcinogenesis.

An interaction between occupational carcinogens and genetic susceptibility factors in determining individual lung cancer risk is biologically plausible, but the interpretation of available studies are limited by the small number of exposed subjects. We selected from the international database on Genetic Susceptibility and Environmental Carcinogens the studies of lung cancer that included information on metabolic polymorphisms and occupational exposures. Adequate data were available for asbestos exposure and GSTM1 (five studies) and GSTT1 (three studies) polymorphisms. For GSTM1, the pooled analysis included 651 cases and 983 controls. The odds ratio (OR) of lung cancer was 2.0 [95% confidence interval (CI) 1.4-2.7] for asbestos exposure and 1.1 (95% CI 0.9-1.4) for GSTM1-null genotype. The OR of interaction between asbestos and GSTM1 polymorphism was 1.1 (95% CI 0.6-2.1) based on 54 cases and 53 controls who were asbestos exposed and GSTM1 null. The case-only approach, which was based on 869 lung cancer cases and had an 80% power to detect an OR of interaction of 1.56, also provided lack of evidence of interaction. The analysis of possible interaction between GSTT1 polymorphism and asbestos exposure in relation to lung cancer was based on 619 cases. The prevalence OR of GSTT1-null genotype and asbestos exposure was 1.1 (95% CI 0.6-2.0). Our results do not support the hypothesis that the risk of lung cancer after asbestos exposure differs according to GSTM1 genotype. The low statistical power of the pooled analysis for GSTT1 genotypes hampered any firm conclusion. No adequate data were available to assess other interactions between occupational exposures and metabolic polymorphisms.     

Acute myelocytic leukemia after exposure to asbestos

While the carcinogenicity of asbestos has been established in malignant mesotheliomas and lung cancers, and has recently been suspected in several other types of cancer, asbestos has not been implicated in the pathogenesis of acute leukemias. This article includes two cases of acute myelocytic leukemia in individuals with a long history of exposure to asbestos. Significant numbers of asbestos bodies were detected in specimens of their lungs and bone marrow. In addition, the kind of asbestos in both organs was crocidolite, which is implicated in carcinogenesis. No asbestos bodies were detected in the bone marrow specimens from a control group consisting of ten patients with lung cancer with similar occupational histories. The role of asbestos exposure in the development of leukemia requires further study.