- Email: [email protected]
Predictors of lung cancer among former asbestos-exposed workers
Accepted Manuscript Title: Predictors of Lung Cancer Among Former Asbestos-Exposed Workers ´ atkowska PhD Zuzanna Szubert PhD Author: Beata Swi˛ Wojciech Sobala MsC Neonila Szeszenia-D˛abrowska Prof. PII: DOI: Reference:
S0169-5002(15)00298-6 http://dx.doi.org/doi:10.1016/j.lungcan.2015.06.013 LUNG 4879
To appear in:
Lung Cancer
Received date: Revised date: Accepted date:
8-12-2014 12-5-2015 14-6-2015
´ atkowska B, Szubert Z, Sobala W, Szeszenia-D˛abrowska Please cite this article as: Swi˛ N, Predictors of Lung Cancer Among Former Asbestos-Exposed Workers, Lung Cancer (2015), http://dx.doi.org/10.1016/j.lungcan.2015.06.013 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Highlights:
We examine the association between occupational asbestos exposure and lung cancer risk Excess risk for lung cancer in the lower lobes was 5 times higher Smokers increased their risk of lung cancer by 2 to 3 times The risk continued to increase until 30 years after cessation of exposure A strategy of smoking cessation potentially would have health promoting effects
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International collaboration for the follow-up of asbestos exposed workers is essential
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Predictors of Lung Cancer Among Former Asbestos-Exposed Workers
Beata Świątkowska, PhD1*, Zuzanna Szubert, PhD1, Wojciech Sobala, MsC1, Neonila Szeszenia-Dąbrowska, Prof.1
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Nofer Institute of Occupational Medicine, Department of Occupational and Environmental
Epidemiology, The Reference Center for Asbestos Exposure & Health Risk Assessment, Św.
Corresponding author: Beata Świątkowska
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*
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Teresy 8, 91-348 Łódź, Poland
Epidemiology, Św. Teresy 8, 91-348 Łódź, Poland
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Nofer Institute of Occupational Medicine, Department of Occupational and Environmental
What is new in the paper:
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e-mail: [email protected], tel (48) (42) 63 14 566, fax (48) (42) 63 14 562
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The manuscript clearly shows a strong association between occupational asbestos exposure and
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lung cancer risk; excess risk for lung cancer in the lower lobes was over five times higher. The risk of lung cancer in the former workers of asbestos-processing plants is about twice higher among the workers with high exposure and among the people with a 20 pack-year history of smoking. A strategy of smoking cessation among individuals exposed to asbestos dust would potentially have health promoting effects.
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Abstract
Objectives Despite 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
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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
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among the workers who were exposed to asbestos dust in the past.
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Material and methods
The assessment was performed based on the case-control studies carried out within a cohort
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including 7,374 former workers of asbestos processing plants, examined over the years 20002013. Analysis of the material was based on the calculation of the odds ratio (OR) using
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branch and time since last exposure.
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conditional logistic regression modeling, adjusted for cigarette smoking, cumulative exposure,
Results
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During the survey period there were 165 cases of lung cancer. Among the individuals who smoked,
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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.
Conclusion
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Our 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.
Keywords
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Occupational exposure; Workers; Smoking; Epidemiology; Asbestos-exposed
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Abbreviations
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OR, odds ratio; CI, confidence interval
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1. Introduction
Lung cancer is the most common cause of cancer-related deaths in men and women, worldwide. In 2008, in the European Union, there were over 289 000 new cases and 254 000 deaths due to lung cancer, which represent about 12% of all the new cases and more than 21% of all deaths due
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to cancer [1]. While cigarette smoking is recognized as the leading cause of lung cancer [2], many occupational exposures, including asbestos, have also been linked to an increased risk of this
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cancer.
Since 1955, associations between asbestos exposure and lung cancer have been well established
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in numerous epidemiological studies [3-7]. The latency period between the first exposure to asbestos fibres and the onset of lung cancer is typically 20-40 years [8]. Clinically and
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pathologically, lung neoplasms induced by asbestos are no different from spontaneously occurring neoplasms in the general population that are caused by smoking. Lung neoplasms caused by
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asbestos malignancies are located in the lower part of the lung - contrary to other neoplasms, the two thirds of which are located in the upper part of the lung field [5, 9].
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Despite extensive literature concerning the risk of the lung cancer incidence in the individuals employed in exposure to asbestos dust, there is still lack of data specifying association between
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the level of exposure and the frequency of cancer occurrence. This stems from, inter alia, lack of
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possibility of quantitative determination of exposure in the case-control studies, in the case of which control groups come from the general population, and the exposure to asbestos is estimated only retrospectively based on the occupational history. Data obtained during examinations of the former workers of asbestos processing plants constitute a unique base allowing quantitative determination of exposure on a basis of retrospective data from individual measurements taken on the employees' work posts and on a basis of data from sanitary-epidemiological stations. The objective of this paper is to assess the influence of cigarette smoking, cumulative asbestos dust concentration, branch and as well as time since the last exposure on the risk of the occurrence of lung cancer among the workers who were exposed to asbestos dust in the past.
2. Material and methods 5 Page 5 of 20
2.1.
Data sources
The study population from which the cases and controls were selected consists of 7,374 former workers of asbestos-processing plants ever employed between 1943 and 1998, i.e., till introduction of the law banning the use of asbestos. The population included the former workers examined at
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least once over the years 2000-2013 within the framework of a health surveillance program for asbestos related diseases.
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From the beginning of the surveillance program in total there were 165 cases of lung cancer in the whole cohort. 130 cases concerned men, while 35 were diagnosed in women. The workers with
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lung cancer were selected as cases and each case had 5 controls selected out of the general study group from the program according to the gender, year of birth and vital status – alive at the
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moment of cancer recognition in the cases. In total, 165 cases had 825 controls, including 650 men
2.1.1. Surveillence program - Amiantus
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and 175 women.
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Prophylactic examinations of the former workers of asbestos-processing plants in Poland are performed as required by the provisions of the Act banning the use of asbestos-containing
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products. In 2000 the Ministry of Health launched the Amiantus Program – a program of
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prophylactic examinations involving employees of all the former Polish asbestos processing plants. Additionally, it is also an epidemiological research on the long-term effects of occupational exposure.
Periodic medical examinations, which aimed at assessment of the respiratory system, were performed by regional occupational medicine centers. A standardized methodology of medical examinations and asbestos-related pathologies recognition, in accordance with commonly approved diagnostic Helsinki Criteria, was developed for the needs of the program [10]. The study documentation includes information about medical interviews, symptoms, lung function testing, basis of the lung cancer diagnosis, radiological x-ray images, histological or cytological confirmation of the disease, histological type, other medical and hospital documentation, and a review of occupational asbestos exposure history using the given company’s records. Information 6 Page 6 of 20
concerning the number of cigarettes smoked now and in the past, and diagnosis of the respiratory system diseases was collected on the developed detailed questionnaires. Vital status information was checked annually by a clinician and was followed up to the end of 2013. Every year about 1,700 former employees reported for medical examinations, of whom approximately 10% were examined for the first time.
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Coordination of the study and supervision was performed by the Reference Centre of Asbestos Exposure and Health Risk Assessment at the Nofer Institute of Occupational Medicine (NIOM) in
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Lodz. The details of the Amiantus surveillance program and data collection system are described
2.2.
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elsewhere [11, 12].
Occupational exposure assessment
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Assessment of exposure was carried out based on the matrix of exposure on the work posts of asbestos processing plants. The work posts were divided into three groups: direct production,
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production service and the remaining workers (mainly administrative personnel). The matrix was developed on a basis of data obtained from the plants or from archives in the case of plants that
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had already been closed down, data from sanitary-epidemiological stations as well as data from the measurements taken by NIOM. Individual measurements on the work posts and stationary
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measurements in the rooms were performed using the gravimetric method in mg/m3 of air. All the
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measurements were conducted in compliance with the national criteria for dust measurement methods in the workplace, regulating maximum allowable concentrations. The method of determination of the number of asbestos fibers per cm3 of air was introduced only in the mid-80s, when the hygienic normative for measurements of concentration of respirable fibers was introduced in Poland and many other countries. Results of the more than 4,000 measurements come from the years 1956 up to 2000. The highest concentration of dust containing asbestos reported in 1950s amounted to 22.2 mg/m3 and to 2.0 mg/m3 in 1990s. The highest concentrations of dust were reported on work posts of burying material, crushing wheels as well as products cutting and polishing. Based on the data from measurements of concentrations of asbestos containing dust, mean concentrations of asbestos dust were assessed for each category of work posts in a given plant 7 Page 7 of 20
during the period from starting production of asbestos containing materials. The whole period of employment of a worker was divided into annual sub-periods and matched with the data on the concentrations of asbestos containing dust. The cumulative exposure index was calculated as a sum of the assigned annual concentrations for the whole period of work. In the case of an employee who worked less than a year, the result was reduced proportionally to the length of the
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working period.
d – cumulative exposure index,
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Where:
µi – mean concentration of asbestos containing dust in a given year and on a given work post (j –
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direct production, production service or remaining posts),
di – time of work during a year (it is one year except for the employees working less than a year).
2.3.
Statistical analysis
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Index of cumulative exposure to asbestos containing dust was expressed in mg/m3 x years.
Odds ratios (OR) of lung cancer and 95% confidence interval (CI) were calculated by applying
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conditional logistic regression modeling adjusted for smoking (cumulative consumption). Final
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multivariate model included all the examined factors - cigarette smoking (pack-years), cumulative exposure, branch and time since the last exposure. Pack-years (i.e., packs of cigarettes smoked per day multiplied by years of smoking) were a variable that expressed smoking. The participants who had never smoked were coded as having less that 1 pack-years. Multiplicative effect of smoking and asbestos exposure was tested by interaction term. Evaluation of all the effects was performed by means of the Wald confidence interval test. Statistical interference was conducted with the significance level equal 0.05. All the analyses were conducted using R programme, version 3.1.0.
3. Results
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3.1.
Cohort characteristics
The cohort included 7,374 formerly asbestos exposed employees who had at least one medical examination performed within the framework of a health surveillance program. Men (63%) prevailed in the group. Generally, the examined individuals started work in asbestos processing plants before being 35 years of age. The mean age at the moment of getting employed was 27.2
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(±8,3) years. About 60% of the individuals from the cohort worked in exposure to asbestos no longer than 15 years. The mean period of exposure amounted to 13,2 (±9,1) years. The most
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numerous were employees of the asbestos-cement plants representing 52.9% of the whole cohort. The cohort consisted mainly of the individuals involved directly in production (57%). About 72% of
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the workers being members of the cohort started work in asbestos industry in the 70s of the
examination was 32.7 (± 10,5) years.
Characterization of lung cancer cases
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3.2.
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previous century or later. The mean period from getting employed to the first asbestos dust
In the group of 165 cases of lung cancer (including 35 women) not even 7% were individuals who
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at the moment of cancer diagnosis were not older than 50 years of age, 26% – these were the individuals between 51-60 years of age, 39% – the individuals aged 61-70 and 28% – the
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individuals older than 70. The individuals who declared ≥ 1 pack-year history of cigarette smoking
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amounted to 74% of the group (Table 1).
Cumulative asbestos dust concentration above 31 mg/m3 x years affected 54% of the workers with lung cancer and 42% of the subjects included in the control group. Among all the cases of lung cancer, the workers of asbestos-cement plants constituted 64% of the whole group. Of all the individuals included in the analysis the lung cancer workers employed before 1969 comprised 47% of the study group, over the years 1970-1979 – 37%, while those employed after 1980 comprised 16%. In the group of people with a diagnosed lung cancer, 66% worked on production work posts, whereas in the control group this percentage was 58%. The period that had elapsed since the last contact with asbestos exposure till the moment of tumor diagnosis was distributed in the examined group as follows: in 32% the time from ceasing
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exposure to asbestos was up to 15 years, in 58% this period was 16-30 years, and in 10% it was over 31 years (Table 1). Among the 165 lung cancer cases, 125 cases (75.7%) were diagnosed as non-small cellular cancer. In the study group, neoplasms located in the upper part of the lung lobe prevailed (75
3.3.
Risk factors of lung cancer in the former asbestos workers
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cases). Neoplasms located in the lower part of the lung lobe occurred in 39 individuals.
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Table 2 shows the results from the multivariate logistic regression analysis. After adjustment for cumulative exposure, branch and time since the last exposure, probability of the occurrence of lung
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cancer in the workers exposed to asbestos dust in the past and smoking more than 20 pack-years was significantly – more than two times – higher (the odds ratio (OR)=2.23; 95% confidence
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interval (CI)=1.45-3.46) in comparison with the non-smoking group (Table 2). Interaction between tobacco smoking and exposure to asbestos dust was not statistically significant (P,
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interaction=0.65). Taking into account neoplasm location, the odds ratio for lung cancer in the lower lobes among the individuals who had smoked more than 20 pack-years relative to the
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individuals who had smoked less than 1 pack-year was OR=3.22 (95%CI: 1.31-7.89) (Table 3). The risk of lung cancer in the upper and middle lobes was twice as high (OR=2.03; 95%CI: 1.22-
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3.36) compared to the lower site. (Table 4).
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The analysis revealed that the risk of lung cancer in the group with the highest exposure (≥31 mg/m3 x years) was two times higher than in the reference group (OR=1.99; 95%CI: 1.22-3.25) (Table 2). The risk of lung cancer in the lower lobe in the group of individuals with a higher exposure level was over 5 times higher (OR=5.64; 95%CI: 1.53-20.77) compared to the patients with a low cumulative asbestos exposure (≤10 mg/m3 x years) (Table 2). The relative risk of lung cancer was significantly increased (OR=1.50; 95% CI: 1.03-2.21) in the case of asbestos-cement branch in comparison with the workers of the remaining asbestos plants (Table 2). In the case of individuals with tumor located in the upper and middle lobes, the OR for asbestos-cement workers was 1.73-fold higher compared to the other workers (OR=1.73; 95%CI: 1.11-2.70) (Table 4).
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The relative risk of lung cancer in the subjects whose exposure to asbestos ceased between 16 and 30 years ago was significantly greater compared to those whose exposure had stopped 2–15 years ago(OR=1.71; 95%CI: 1.14-2.55) (Table 2). The risk of lung cancer in the upper and middle lobes 16–30 years after cessation of exposure was almost the same as for the general location (OR=1.60; 95%CI: 1.01-2.52). The estimated risk of lung cancer tended to decrease with the
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increasing time since the last exposure (Table 4).
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4. Discussion
The present study confirms the strong evidence that lung cancer risk is associated with asbestos
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exposure and that the risk increases along with the increasing exposure. The risk of lung cancer located in the lower lobe was over 5 times significantly higher (OR=5.64; 95%CI: 1.53-20.77) in the
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group of workers with the highest exposure in comparison with the control group. A dose-response relationship between asbestos exposure and lung cancer risk has been also observed in many
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other studies [6, 7, 13].
In the case-control study carried out in France, a significantly increased odds ratio for lung cancer
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in the 2 highest categories of asbestos dust exposure: OR=2.0 (95%CI: 1.3-3.2) and OR=1.9 (95%CI:1.2-3.0) has been shown [14]. Combined results of the 2 case-control studies, which were
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performed in Canada, have shown the risk of lung cancer to be almost 3 times higher (OR= 2.98; 95%CI: 1.28-6.96) in the case of exposure to asbestos longer than 20 years [15]. The case-control study in China has reported excess risk of lung cancer (OR=3.66; 95% CI: 1.61-8.29) for high exposure [16]. A recent population case-control study has also provided support for a doseresponse relationship between asbestos exposure and lung cancer [17]. Results of the 2 case-control studies, carried out in Germany, have indicated over 2 times higher risk for 8 and more years of work (OR=2.4; 95%CI: 1.7-3.4) in comparison with the group of the not exposed individuals. The study has revealed, that the risk of lung cancer increases soon after starting exposure to asbestos with the maximum effect after 10-15 years from the last exposure [18]. The results of our study showed that the risk of lung cancer continued to increase until 30 years after cessation of exposure and started to decline many years after the last exposure. 11 Page 11 of 20
Both tobacco smoke and asbestos are carcinogenic factors, thus, how they both interact with each other to increase the risk of lung cancer is an issue frequently discussed in literature. Most studies have focused on 2 hypotheses on the interactive effects: one – multiplicative, which implies that asbestos exposure increases the risk of lung cancer by the same factor in smokers and nonsmokers alike, and the second – that the effects of asbestos exposure and smoking are additive
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[19, 20]. Some recent studies have suggested that the combined effect of asbestos exposure and smoking is more than additive [21] and a recent systematic review has shown that the interaction
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between asbestos and smoking regarding lung cancer risk is between additive and multiplicative [7].
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The results of our study indicated a significantly higher lung cancer risk in the group of people who smoked more than 20 pack-years (OR=2.23), after inclusion of cumulative exposure, branch and
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the time since the last exposure in asbestos processing plants. Observations do not deviate from the multiplicative model, however, the interaction between tobacco smoking and exposure to
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asbestos dust was not statistically significant. Similar observations have been reported in many other studies [22, 23].
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The presented study results have some limitations. Firstly, the individuals interested in participation in the program reported for medical examinations spontaneously. Selection associated with the
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participation in the program may be a result of their willingness to diagnose an occupational
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disease and to receive a related to it financial compensation, or of a worse health status and sensation of ailments on the side of the respiratory tract. At baseline, in the year 2000 the cohort of people ever employed in asbestos-processing plants, eligible for the Amiantus Program consisted of about 22 thousand former employees. Under the programe, over the period 2000-2013, 7,374 people participated in the medical examinations, so we were able to examine about 34% of the people who had ever been exposed in asbestos processing plants in the period 1943-1998. Secondly, assessment of exposure was performed on the basis of retrospective data from individual measurements taken at work posts and stationary measurements taken by the use of the gravimetric method for respirable dust. The choice of this method of exposure assessment was justified by the fact that the study population consisted of the individuals ever employed in the
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examined plants and thus, also during the period before introduction of measurement of the number of respirable fibers, which started only in the mid-80s of the twentieth century. The previously mentioned limitations should be taken into consideration when interpreting the results. However, the large number of workers examined in accordance with the standardized criteria and standard procedures in the whole country, and a long term follow-up are significant
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positive values of the study.
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5. Conclusions
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In conclusion, lung cancer may occur long time after termination of asbestos exposure, so the follow-up examinations of asbestos exposure workers are necessary, e.g. from the compensation
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point of view. The results of our surveillance study enabled identification of patients at a high risk of lung cancer and could be used to create general follow-up scheme for detection of lung cancer in
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the former asbestos exposed workers. International collaboration in the research for follow-up of
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asbestos exposed workers and screening of asbestos-related diseases is essential.
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Conflicts of interest statement
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Authors declare that there are no conflicts of interest
Acknowledgements
The paper was created as part of the task ‘Risk assessment for incidence and death of asbestosrelated diseases among persons occupationally exposed to asbestos dust on the basis of longterm epidemiological observation’ (NIOM, 10.14). The authors of this publication would like to thank all the people who cooperated in implementation of the ‘Amiantus’ project, particularly the physicians who performed periodic examinations in the regional centers of occupational medicine and those who encoded radiological changes.
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4. Gustavsson P, Jakobsson R, Nyberg F, Pershagen G, Järup L, Schéele P. Occupational exposure and lung cancer risk: a population-based referent study in Sweden. Am J Epidemiol.
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5. Henderson DW, Rödelsperge K, Woitowitz HJ, Leigh J. After Helsinki: a multidisciplinary review
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Agency for Research on Cancer (IARC), 2012. 219–309. 7. Nielsen LS, Bælum J, Rasmussen J, Dahl S, Olsen KE, Albin M, Hansen NC, Sherson D.
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Occupational asbestos exposure and lung cancer--a systematic review of the literature. Arch Environ Occup Health. 2014;69:191-206. 8. Valic F. The asbestos dilemma: I. Assessment of risk. Arh Hig Rada Toksikol. 2002;53:153167.
9. Anttila S, Karjalainen A, Taikina-aho O, Kyyrönen P, Vainio H. Lung cancer in the lower lobe is associated with pulmonary asbestos fiber count and fiber size. Environ Health Perspect. 1993;101:166–170. 10. Consensus Report. Asbestos. Asbestosis and Cancer: the Helsinki Criteria for diagnosis and attribution. Scand J Work Environ Health. 1997;23:311-316. 11. Szeszenia-Dabrowska N, Szubert Z. Programme of prophylactic medical examinations of former asbestos workers – Amiantus. Med Pr. 2002;6:451-456. 14 Page 14 of 20
12. Szeszenia-Dąbrowska N, Świątkowska B, Szubert Z, Wilczyńska U. Asbestos in Poland: occupational health problems. Int J Occup Med Environ Health. 2011;24:142-52. 13. Hillerdal G, Henderson DW. Asbestos, asbestosis, pleural plaques and lung cancer. Scand J Work Environ Health. 1997;23:93-103. 14. Imbernon E, Goldberg M, Bonenfont S, Chevalier A, Guenel P, Vatre R, Dehaye J.
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Occupational Respiratory Cancer and Exposure to Asbestos: A Case-Control Study in Cohort of Workers in the Electricity and Gas Industry. Am J Ind Med. 1995;28:339-352.
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15. Pintos J, Parent ME, Rousseau MC, Case BW, Siemiatycki J. Occupational Exposure to Asbestos and Man-Made Vitreous Fibers. and Risk of Lung Cancer: Evidence From Two Case-
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Control Studies in Mantreal. Canada. J Occup Environ Med. 2008;50:1273-1281. 16. Yano E, Wang X, Wang M, Qiu H, Wang Z. Lung cancer mortality from exposure to chrysotile
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asbestos and smoking: a case-control study within a cohort in China. Occup Environ Med. 2010;67:867-871.
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17. Villeneuve PJ, Harris SA, Parent ME, Johnson KC. Occupational exposure to asbestos and lung cancer in men: evidence from a population-based case-control study in eight Canadian
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18. Hauptmann M, Pohlabeln H, Lubin JH, Jockel KH, Ahrens W, Bruske-Hohlfeld I, Wichmann H.
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The exposure-time-response relationship between occupational asbestos exposure and lung
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cancer in two German case-control studies. Am J Ind Med. 2002;41:89-97. 19. Liddell FDK. The Interaction of Asbestos and Smoking in Lung Cancer. Ann Occup Hyg. 2001;45:341-356.
20. Berry G, Liddell FDK. The Interaction of Asbestos and Smoking in Lung Cancer: A modified measure of effect. Ann Occup Hyg. 2004;48:459-462. 21. Frost G, Darnton A, Harding AH. The effect of smoking on the risk of lung cancer mortality for asbestos workers in Great Britain (1971-2005). Ann Occup Hyg. 2011;55:239-47. 22. Reid A, de Klerk NH, Ambrosini GL, Berry G, Musk AW. The risk of lung cancer with increasing time since ceasing exposure to asbestos and quitting smoking. Occup Environ Med. 2009;63:509-512.
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23. Markowitz SB, Levin SM. Miller A, Morabia A. Asbestos. asbestosis. smoking. and lung cancer. New findings from the North American insulator cohort. Am J Respir Crit Care Med.
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Table1. Selected characteristics of the case and control subjects Case subjects
Control subjects
(N=165)
(N=825)
Variable N
%
N
%
Female
35
21.2
650
21.2
Male
130
78.8
≤ 1937
54
32.7
270
32.7
1938-1947
65
39.4
325
39.4
1978-1969
46
27.9
230
27.9
43
26.1
317
38.4
31
18.8
158
19.2
91
55.1
350
42.4
31
19.1
227
28.3
43
26.5
236
29.4
88
54.4
339
42.3
60
36.4
391
47.4
105
63.6
434
52.6
2-15
52
31.5
339
41.1
16-30
96
58.2
397
48.1
≥ 31
17
10.3
89
10.8
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Smoking (pack-year) No
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1-20 ≥ 21
175
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Calendar year of birth (years)
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Gender
78.8
ed
Cumulative exposure index (mg/m3 x years)a ≤ 10
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11-30
Branch other
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≥ 31
asbestos-cement
Time since termination of employment (years)
Notes: N = number of patients; other = other types of plants a
No data for 3 cases and 23 controls
17 Page 17 of 20
Table 2. Odds ratios (ORs) for lung cancer among the former workers of asbestos processing plants ORa
95%CI
ORb
95%CI
No
1.00
1.00
1-20
1.50c
0.90-2.47
1.67
1.00-2.80
≥ 21
2.07c
1.36-3.15
2.23
≤ 10
1.00
11-30
1.35
0.82-2.23
1.38
0.83-2.29
≥ 31
2.09
1.31-3.34
1.99
1.22-3.25
Characteristic
1.45-3.46
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Cumulative exposure index (mg/m3 x years)d
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Smoking (pack-year)
other
1.00
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1.00
1.00
asbestos-cement plants
1.67
1.17-2.39
1.50
1.03-2.21
1.00
1.00
1.69
1.15-2.49
1.71
1.14-2.55
1.33
0.72-2.47
1.30
0.69-2.49
16-30
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≥ 31
pt
2-15
ed
Time since termination of employment (years)
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Branch
Notes: OR = odds ratio; CI = confidence interval; other = other types of plants a
Adjusted for pack-year
b
All variables were included in the multivariate model
c
Unadjusted
d
No data for 3 cases and 23 controls
18 Page 18 of 20
Table 3. Odds ratios (ORs) for lung cancer in the lower lobe among the former workers of asbestos processing plants Cases
Controls
ORa
95%CI
ORb
95%CI
1.00
(N=39)
(N=195)
No
11
91
1.00
1-20
6
40
1.24c
0.44-3.51
1.08
0.36-3.28
≥ 21
22
64
3.35c
1.43-7.83
3.22
1.31-7.89
≤ 10
3
46
1.00
11-30
6
59
1.49
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Characteristic
≥ 31
29
87
5.06
other
15
83
asbestos-cement plants
24
112
cr
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Smoking (pack-year)
Cumulative exposure index (mg/m3 x years)d
1.00
0.36-6.22
1.53
0.36-6.60
1.42-18.03
5.64
1.53-20.77
1.00
1.00
1.19
0.58-2.44
1.00
0.44-2.26
91
1.00
1.00
85
1.97
0.85-4.60
2.31
0.92-5.79
19
0.99
0.23-4.21
1.03
0.22-4.73
an
13
pt
2-15
23
Ac ce
16-30 ≥ 31
ed
Time since termination of employment (years)
M
Branch
3
Notes: OR = odds ratio; CI = confidence interval; other = other types of plants a
Adjusted for pack-year
b
All variables were included in the multivariate model
c
Unadjusted
d
No data for 1 cases and 3 controls
19 Page 19 of 20
Table 4. Odds ratios (ORs) for lung cancer in the upper and middle lobes among the former workers of asbestos processing plants Cases
Controls
ORa
95%CI
ORb
95%CI
1.00
(N=126)
(N=630)
No
32
226
1.00
1-20
25
118
1.54c
0.87-2.76
1.78
0.98-3.24
≥ 21
69
286
1.79c
1.11-2.90
2.03
1.22-3.36
≤ 10
28
181
1.00
11-30
37
177
1.33
us
Characteristic
≥ 31
59
252
1.65
other
45
308
asbestos-cement plants
81
322
cr
ip t
Smoking (pack-year)
1.00
0.78-2.28
1.34
0.77-2.33
0.98-2.79
1.48
0.85-2.58
1.00
1.00
1.85
1.23-2.80
1.73
1.11-2.70
248
1.00
1.00
312
1.60
1.02-2.49
1.60
1.01-2.52
14
70
1.37
0.69-2.74
1.31
0.63-2.71
an
pt
Cumulative exposure index (mg/m3 x years)d
2-15
39
≥ 31
73
Ac ce
16-30
ed
Time since termination of employment (years)
M
Branch
Notes: OR = odds ratio; CI = confidence interval; other = other types of plants a
Adjusted for pack-year
b
All variables were included in the multivariate model
c
Unadjusted
d
No data for 2 cases and 20 controls
20 Page 20 of 20
S0169-5002(15)00298-6 http://dx.doi.org/doi:10.1016/j.lungcan.2015.06.013 LUNG 4879
To appear in:
Lung Cancer
Received date: Revised date: Accepted date:
8-12-2014 12-5-2015 14-6-2015
´ atkowska B, Szubert Z, Sobala W, Szeszenia-D˛abrowska Please cite this article as: Swi˛ N, Predictors of Lung Cancer Among Former Asbestos-Exposed Workers, Lung Cancer (2015), http://dx.doi.org/10.1016/j.lungcan.2015.06.013 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Highlights:
We examine the association between occupational asbestos exposure and lung cancer risk Excess risk for lung cancer in the lower lobes was 5 times higher Smokers increased their risk of lung cancer by 2 to 3 times The risk continued to increase until 30 years after cessation of exposure A strategy of smoking cessation potentially would have health promoting effects
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ed
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an
us
cr
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International collaboration for the follow-up of asbestos exposed workers is essential
1 Page 1 of 20
Predictors of Lung Cancer Among Former Asbestos-Exposed Workers
Beata Świątkowska, PhD1*, Zuzanna Szubert, PhD1, Wojciech Sobala, MsC1, Neonila Szeszenia-Dąbrowska, Prof.1
1
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Nofer Institute of Occupational Medicine, Department of Occupational and Environmental
Epidemiology, The Reference Center for Asbestos Exposure & Health Risk Assessment, Św.
Corresponding author: Beata Świątkowska
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*
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Teresy 8, 91-348 Łódź, Poland
Epidemiology, Św. Teresy 8, 91-348 Łódź, Poland
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Nofer Institute of Occupational Medicine, Department of Occupational and Environmental
What is new in the paper:
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e-mail: [email protected], tel (48) (42) 63 14 566, fax (48) (42) 63 14 562
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The manuscript clearly shows a strong association between occupational asbestos exposure and
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lung cancer risk; excess risk for lung cancer in the lower lobes was over five times higher. The risk of lung cancer in the former workers of asbestos-processing plants is about twice higher among the workers with high exposure and among the people with a 20 pack-year history of smoking. A strategy of smoking cessation among individuals exposed to asbestos dust would potentially have health promoting effects.
2 Page 2 of 20
Abstract
Objectives Despite 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
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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
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among the workers who were exposed to asbestos dust in the past.
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Material and methods
The assessment was performed based on the case-control studies carried out within a cohort
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including 7,374 former workers of asbestos processing plants, examined over the years 20002013. Analysis of the material was based on the calculation of the odds ratio (OR) using
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branch and time since last exposure.
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conditional logistic regression modeling, adjusted for cigarette smoking, cumulative exposure,
Results
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During the survey period there were 165 cases of lung cancer. Among the individuals who smoked,
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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.
Conclusion
3 Page 3 of 20
Our 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.
Keywords
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Occupational exposure; Workers; Smoking; Epidemiology; Asbestos-exposed
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Abbreviations
Ac ce
pt
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M
an
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OR, odds ratio; CI, confidence interval
4 Page 4 of 20
1. Introduction
Lung cancer is the most common cause of cancer-related deaths in men and women, worldwide. In 2008, in the European Union, there were over 289 000 new cases and 254 000 deaths due to lung cancer, which represent about 12% of all the new cases and more than 21% of all deaths due
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to cancer [1]. While cigarette smoking is recognized as the leading cause of lung cancer [2], many occupational exposures, including asbestos, have also been linked to an increased risk of this
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cancer.
Since 1955, associations between asbestos exposure and lung cancer have been well established
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in numerous epidemiological studies [3-7]. The latency period between the first exposure to asbestos fibres and the onset of lung cancer is typically 20-40 years [8]. Clinically and
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pathologically, lung neoplasms induced by asbestos are no different from spontaneously occurring neoplasms in the general population that are caused by smoking. Lung neoplasms caused by
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asbestos malignancies are located in the lower part of the lung - contrary to other neoplasms, the two thirds of which are located in the upper part of the lung field [5, 9].
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Despite extensive literature concerning the risk of the lung cancer incidence in the individuals employed in exposure to asbestos dust, there is still lack of data specifying association between
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the level of exposure and the frequency of cancer occurrence. This stems from, inter alia, lack of
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possibility of quantitative determination of exposure in the case-control studies, in the case of which control groups come from the general population, and the exposure to asbestos is estimated only retrospectively based on the occupational history. Data obtained during examinations of the former workers of asbestos processing plants constitute a unique base allowing quantitative determination of exposure on a basis of retrospective data from individual measurements taken on the employees' work posts and on a basis of data from sanitary-epidemiological stations. The objective of this paper is to assess the influence of cigarette smoking, cumulative asbestos dust concentration, branch and as well as time since the last exposure on the risk of the occurrence of lung cancer among the workers who were exposed to asbestos dust in the past.
2. Material and methods 5 Page 5 of 20
2.1.
Data sources
The study population from which the cases and controls were selected consists of 7,374 former workers of asbestos-processing plants ever employed between 1943 and 1998, i.e., till introduction of the law banning the use of asbestos. The population included the former workers examined at
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least once over the years 2000-2013 within the framework of a health surveillance program for asbestos related diseases.
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From the beginning of the surveillance program in total there were 165 cases of lung cancer in the whole cohort. 130 cases concerned men, while 35 were diagnosed in women. The workers with
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lung cancer were selected as cases and each case had 5 controls selected out of the general study group from the program according to the gender, year of birth and vital status – alive at the
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moment of cancer recognition in the cases. In total, 165 cases had 825 controls, including 650 men
2.1.1. Surveillence program - Amiantus
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and 175 women.
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Prophylactic examinations of the former workers of asbestos-processing plants in Poland are performed as required by the provisions of the Act banning the use of asbestos-containing
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products. In 2000 the Ministry of Health launched the Amiantus Program – a program of
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prophylactic examinations involving employees of all the former Polish asbestos processing plants. Additionally, it is also an epidemiological research on the long-term effects of occupational exposure.
Periodic medical examinations, which aimed at assessment of the respiratory system, were performed by regional occupational medicine centers. A standardized methodology of medical examinations and asbestos-related pathologies recognition, in accordance with commonly approved diagnostic Helsinki Criteria, was developed for the needs of the program [10]. The study documentation includes information about medical interviews, symptoms, lung function testing, basis of the lung cancer diagnosis, radiological x-ray images, histological or cytological confirmation of the disease, histological type, other medical and hospital documentation, and a review of occupational asbestos exposure history using the given company’s records. Information 6 Page 6 of 20
concerning the number of cigarettes smoked now and in the past, and diagnosis of the respiratory system diseases was collected on the developed detailed questionnaires. Vital status information was checked annually by a clinician and was followed up to the end of 2013. Every year about 1,700 former employees reported for medical examinations, of whom approximately 10% were examined for the first time.
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Coordination of the study and supervision was performed by the Reference Centre of Asbestos Exposure and Health Risk Assessment at the Nofer Institute of Occupational Medicine (NIOM) in
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Lodz. The details of the Amiantus surveillance program and data collection system are described
2.2.
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elsewhere [11, 12].
Occupational exposure assessment
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Assessment of exposure was carried out based on the matrix of exposure on the work posts of asbestos processing plants. The work posts were divided into three groups: direct production,
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production service and the remaining workers (mainly administrative personnel). The matrix was developed on a basis of data obtained from the plants or from archives in the case of plants that
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had already been closed down, data from sanitary-epidemiological stations as well as data from the measurements taken by NIOM. Individual measurements on the work posts and stationary
pt
measurements in the rooms were performed using the gravimetric method in mg/m3 of air. All the
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measurements were conducted in compliance with the national criteria for dust measurement methods in the workplace, regulating maximum allowable concentrations. The method of determination of the number of asbestos fibers per cm3 of air was introduced only in the mid-80s, when the hygienic normative for measurements of concentration of respirable fibers was introduced in Poland and many other countries. Results of the more than 4,000 measurements come from the years 1956 up to 2000. The highest concentration of dust containing asbestos reported in 1950s amounted to 22.2 mg/m3 and to 2.0 mg/m3 in 1990s. The highest concentrations of dust were reported on work posts of burying material, crushing wheels as well as products cutting and polishing. Based on the data from measurements of concentrations of asbestos containing dust, mean concentrations of asbestos dust were assessed for each category of work posts in a given plant 7 Page 7 of 20
during the period from starting production of asbestos containing materials. The whole period of employment of a worker was divided into annual sub-periods and matched with the data on the concentrations of asbestos containing dust. The cumulative exposure index was calculated as a sum of the assigned annual concentrations for the whole period of work. In the case of an employee who worked less than a year, the result was reduced proportionally to the length of the
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working period.
d – cumulative exposure index,
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Where:
µi – mean concentration of asbestos containing dust in a given year and on a given work post (j –
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direct production, production service or remaining posts),
di – time of work during a year (it is one year except for the employees working less than a year).
2.3.
Statistical analysis
ed
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Index of cumulative exposure to asbestos containing dust was expressed in mg/m3 x years.
Odds ratios (OR) of lung cancer and 95% confidence interval (CI) were calculated by applying
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conditional logistic regression modeling adjusted for smoking (cumulative consumption). Final
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multivariate model included all the examined factors - cigarette smoking (pack-years), cumulative exposure, branch and time since the last exposure. Pack-years (i.e., packs of cigarettes smoked per day multiplied by years of smoking) were a variable that expressed smoking. The participants who had never smoked were coded as having less that 1 pack-years. Multiplicative effect of smoking and asbestos exposure was tested by interaction term. Evaluation of all the effects was performed by means of the Wald confidence interval test. Statistical interference was conducted with the significance level equal 0.05. All the analyses were conducted using R programme, version 3.1.0.
3. Results
8 Page 8 of 20
3.1.
Cohort characteristics
The cohort included 7,374 formerly asbestos exposed employees who had at least one medical examination performed within the framework of a health surveillance program. Men (63%) prevailed in the group. Generally, the examined individuals started work in asbestos processing plants before being 35 years of age. The mean age at the moment of getting employed was 27.2
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(±8,3) years. About 60% of the individuals from the cohort worked in exposure to asbestos no longer than 15 years. The mean period of exposure amounted to 13,2 (±9,1) years. The most
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numerous were employees of the asbestos-cement plants representing 52.9% of the whole cohort. The cohort consisted mainly of the individuals involved directly in production (57%). About 72% of
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the workers being members of the cohort started work in asbestos industry in the 70s of the
examination was 32.7 (± 10,5) years.
Characterization of lung cancer cases
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3.2.
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previous century or later. The mean period from getting employed to the first asbestos dust
In the group of 165 cases of lung cancer (including 35 women) not even 7% were individuals who
ed
at the moment of cancer diagnosis were not older than 50 years of age, 26% – these were the individuals between 51-60 years of age, 39% – the individuals aged 61-70 and 28% – the
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individuals older than 70. The individuals who declared ≥ 1 pack-year history of cigarette smoking
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amounted to 74% of the group (Table 1).
Cumulative asbestos dust concentration above 31 mg/m3 x years affected 54% of the workers with lung cancer and 42% of the subjects included in the control group. Among all the cases of lung cancer, the workers of asbestos-cement plants constituted 64% of the whole group. Of all the individuals included in the analysis the lung cancer workers employed before 1969 comprised 47% of the study group, over the years 1970-1979 – 37%, while those employed after 1980 comprised 16%. In the group of people with a diagnosed lung cancer, 66% worked on production work posts, whereas in the control group this percentage was 58%. The period that had elapsed since the last contact with asbestos exposure till the moment of tumor diagnosis was distributed in the examined group as follows: in 32% the time from ceasing
9 Page 9 of 20
exposure to asbestos was up to 15 years, in 58% this period was 16-30 years, and in 10% it was over 31 years (Table 1). Among the 165 lung cancer cases, 125 cases (75.7%) were diagnosed as non-small cellular cancer. In the study group, neoplasms located in the upper part of the lung lobe prevailed (75
3.3.
Risk factors of lung cancer in the former asbestos workers
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cases). Neoplasms located in the lower part of the lung lobe occurred in 39 individuals.
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Table 2 shows the results from the multivariate logistic regression analysis. After adjustment for cumulative exposure, branch and time since the last exposure, probability of the occurrence of lung
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cancer in the workers exposed to asbestos dust in the past and smoking more than 20 pack-years was significantly – more than two times – higher (the odds ratio (OR)=2.23; 95% confidence
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interval (CI)=1.45-3.46) in comparison with the non-smoking group (Table 2). Interaction between tobacco smoking and exposure to asbestos dust was not statistically significant (P,
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interaction=0.65). Taking into account neoplasm location, the odds ratio for lung cancer in the lower lobes among the individuals who had smoked more than 20 pack-years relative to the
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individuals who had smoked less than 1 pack-year was OR=3.22 (95%CI: 1.31-7.89) (Table 3). The risk of lung cancer in the upper and middle lobes was twice as high (OR=2.03; 95%CI: 1.22-
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3.36) compared to the lower site. (Table 4).
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The analysis revealed that the risk of lung cancer in the group with the highest exposure (≥31 mg/m3 x years) was two times higher than in the reference group (OR=1.99; 95%CI: 1.22-3.25) (Table 2). The risk of lung cancer in the lower lobe in the group of individuals with a higher exposure level was over 5 times higher (OR=5.64; 95%CI: 1.53-20.77) compared to the patients with a low cumulative asbestos exposure (≤10 mg/m3 x years) (Table 2). The relative risk of lung cancer was significantly increased (OR=1.50; 95% CI: 1.03-2.21) in the case of asbestos-cement branch in comparison with the workers of the remaining asbestos plants (Table 2). In the case of individuals with tumor located in the upper and middle lobes, the OR for asbestos-cement workers was 1.73-fold higher compared to the other workers (OR=1.73; 95%CI: 1.11-2.70) (Table 4).
10 Page 10 of 20
The relative risk of lung cancer in the subjects whose exposure to asbestos ceased between 16 and 30 years ago was significantly greater compared to those whose exposure had stopped 2–15 years ago(OR=1.71; 95%CI: 1.14-2.55) (Table 2). The risk of lung cancer in the upper and middle lobes 16–30 years after cessation of exposure was almost the same as for the general location (OR=1.60; 95%CI: 1.01-2.52). The estimated risk of lung cancer tended to decrease with the
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increasing time since the last exposure (Table 4).
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4. Discussion
The present study confirms the strong evidence that lung cancer risk is associated with asbestos
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exposure and that the risk increases along with the increasing exposure. The risk of lung cancer located in the lower lobe was over 5 times significantly higher (OR=5.64; 95%CI: 1.53-20.77) in the
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group of workers with the highest exposure in comparison with the control group. A dose-response relationship between asbestos exposure and lung cancer risk has been also observed in many
ed
other studies [6, 7, 13].
In the case-control study carried out in France, a significantly increased odds ratio for lung cancer
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in the 2 highest categories of asbestos dust exposure: OR=2.0 (95%CI: 1.3-3.2) and OR=1.9 (95%CI:1.2-3.0) has been shown [14]. Combined results of the 2 case-control studies, which were
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performed in Canada, have shown the risk of lung cancer to be almost 3 times higher (OR= 2.98; 95%CI: 1.28-6.96) in the case of exposure to asbestos longer than 20 years [15]. The case-control study in China has reported excess risk of lung cancer (OR=3.66; 95% CI: 1.61-8.29) for high exposure [16]. A recent population case-control study has also provided support for a doseresponse relationship between asbestos exposure and lung cancer [17]. Results of the 2 case-control studies, carried out in Germany, have indicated over 2 times higher risk for 8 and more years of work (OR=2.4; 95%CI: 1.7-3.4) in comparison with the group of the not exposed individuals. The study has revealed, that the risk of lung cancer increases soon after starting exposure to asbestos with the maximum effect after 10-15 years from the last exposure [18]. The results of our study showed that the risk of lung cancer continued to increase until 30 years after cessation of exposure and started to decline many years after the last exposure. 11 Page 11 of 20
Both tobacco smoke and asbestos are carcinogenic factors, thus, how they both interact with each other to increase the risk of lung cancer is an issue frequently discussed in literature. Most studies have focused on 2 hypotheses on the interactive effects: one – multiplicative, which implies that asbestos exposure increases the risk of lung cancer by the same factor in smokers and nonsmokers alike, and the second – that the effects of asbestos exposure and smoking are additive
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[19, 20]. Some recent studies have suggested that the combined effect of asbestos exposure and smoking is more than additive [21] and a recent systematic review has shown that the interaction
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between asbestos and smoking regarding lung cancer risk is between additive and multiplicative [7].
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The results of our study indicated a significantly higher lung cancer risk in the group of people who smoked more than 20 pack-years (OR=2.23), after inclusion of cumulative exposure, branch and
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the time since the last exposure in asbestos processing plants. Observations do not deviate from the multiplicative model, however, the interaction between tobacco smoking and exposure to
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asbestos dust was not statistically significant. Similar observations have been reported in many other studies [22, 23].
ed
The presented study results have some limitations. Firstly, the individuals interested in participation in the program reported for medical examinations spontaneously. Selection associated with the
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participation in the program may be a result of their willingness to diagnose an occupational
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disease and to receive a related to it financial compensation, or of a worse health status and sensation of ailments on the side of the respiratory tract. At baseline, in the year 2000 the cohort of people ever employed in asbestos-processing plants, eligible for the Amiantus Program consisted of about 22 thousand former employees. Under the programe, over the period 2000-2013, 7,374 people participated in the medical examinations, so we were able to examine about 34% of the people who had ever been exposed in asbestos processing plants in the period 1943-1998. Secondly, assessment of exposure was performed on the basis of retrospective data from individual measurements taken at work posts and stationary measurements taken by the use of the gravimetric method for respirable dust. The choice of this method of exposure assessment was justified by the fact that the study population consisted of the individuals ever employed in the
12 Page 12 of 20
examined plants and thus, also during the period before introduction of measurement of the number of respirable fibers, which started only in the mid-80s of the twentieth century. The previously mentioned limitations should be taken into consideration when interpreting the results. However, the large number of workers examined in accordance with the standardized criteria and standard procedures in the whole country, and a long term follow-up are significant
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positive values of the study.
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5. Conclusions
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In conclusion, lung cancer may occur long time after termination of asbestos exposure, so the follow-up examinations of asbestos exposure workers are necessary, e.g. from the compensation
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point of view. The results of our surveillance study enabled identification of patients at a high risk of lung cancer and could be used to create general follow-up scheme for detection of lung cancer in
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the former asbestos exposed workers. International collaboration in the research for follow-up of
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asbestos exposed workers and screening of asbestos-related diseases is essential.
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Conflicts of interest statement
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Authors declare that there are no conflicts of interest
Acknowledgements
The paper was created as part of the task ‘Risk assessment for incidence and death of asbestosrelated diseases among persons occupationally exposed to asbestos dust on the basis of longterm epidemiological observation’ (NIOM, 10.14). The authors of this publication would like to thank all the people who cooperated in implementation of the ‘Amiantus’ project, particularly the physicians who performed periodic examinations in the regional centers of occupational medicine and those who encoded radiological changes.
13 Page 13 of 20
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North Am. 2012;50:863-876. 3. Boffetta P. Health effects of asbestos exposure in humans: a quantitative assessment. Med
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Lav. 1998;89:471-80
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4. Gustavsson P, Jakobsson R, Nyberg F, Pershagen G, Järup L, Schéele P. Occupational exposure and lung cancer risk: a population-based referent study in Sweden. Am J Epidemiol.
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2000;152:32-40.
5. Henderson DW, Rödelsperge K, Woitowitz HJ, Leigh J. After Helsinki: a multidisciplinary review
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of the relationship between asbestos exposure and lung cancer. with emphasis on studies published during 1997-2004. Pathology. 2004;36:517-50.
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6. IARC. Asbestos (Chrysotile, Amosite, Crocidolite,Tremolite, Actinolite and Anthophyllite). In: A review of human carcinogens: arsenic, metals, fibres, and dusts. Lyon, France: International
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Agency for Research on Cancer (IARC), 2012. 219–309. 7. Nielsen LS, Bælum J, Rasmussen J, Dahl S, Olsen KE, Albin M, Hansen NC, Sherson D.
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Occupational asbestos exposure and lung cancer--a systematic review of the literature. Arch Environ Occup Health. 2014;69:191-206. 8. Valic F. The asbestos dilemma: I. Assessment of risk. Arh Hig Rada Toksikol. 2002;53:153167.
9. Anttila S, Karjalainen A, Taikina-aho O, Kyyrönen P, Vainio H. Lung cancer in the lower lobe is associated with pulmonary asbestos fiber count and fiber size. Environ Health Perspect. 1993;101:166–170. 10. Consensus Report. Asbestos. Asbestosis and Cancer: the Helsinki Criteria for diagnosis and attribution. Scand J Work Environ Health. 1997;23:311-316. 11. Szeszenia-Dabrowska N, Szubert Z. Programme of prophylactic medical examinations of former asbestos workers – Amiantus. Med Pr. 2002;6:451-456. 14 Page 14 of 20
12. Szeszenia-Dąbrowska N, Świątkowska B, Szubert Z, Wilczyńska U. Asbestos in Poland: occupational health problems. Int J Occup Med Environ Health. 2011;24:142-52. 13. Hillerdal G, Henderson DW. Asbestos, asbestosis, pleural plaques and lung cancer. Scand J Work Environ Health. 1997;23:93-103. 14. Imbernon E, Goldberg M, Bonenfont S, Chevalier A, Guenel P, Vatre R, Dehaye J.
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Occupational Respiratory Cancer and Exposure to Asbestos: A Case-Control Study in Cohort of Workers in the Electricity and Gas Industry. Am J Ind Med. 1995;28:339-352.
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15. Pintos J, Parent ME, Rousseau MC, Case BW, Siemiatycki J. Occupational Exposure to Asbestos and Man-Made Vitreous Fibers. and Risk of Lung Cancer: Evidence From Two Case-
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Control Studies in Mantreal. Canada. J Occup Environ Med. 2008;50:1273-1281. 16. Yano E, Wang X, Wang M, Qiu H, Wang Z. Lung cancer mortality from exposure to chrysotile
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asbestos and smoking: a case-control study within a cohort in China. Occup Environ Med. 2010;67:867-871.
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17. Villeneuve PJ, Harris SA, Parent ME, Johnson KC. Occupational exposure to asbestos and lung cancer in men: evidence from a population-based case-control study in eight Canadian
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provinces. BMC Cancer. 2012;12:595.
18. Hauptmann M, Pohlabeln H, Lubin JH, Jockel KH, Ahrens W, Bruske-Hohlfeld I, Wichmann H.
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The exposure-time-response relationship between occupational asbestos exposure and lung
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cancer in two German case-control studies. Am J Ind Med. 2002;41:89-97. 19. Liddell FDK. The Interaction of Asbestos and Smoking in Lung Cancer. Ann Occup Hyg. 2001;45:341-356.
20. Berry G, Liddell FDK. The Interaction of Asbestos and Smoking in Lung Cancer: A modified measure of effect. Ann Occup Hyg. 2004;48:459-462. 21. Frost G, Darnton A, Harding AH. The effect of smoking on the risk of lung cancer mortality for asbestos workers in Great Britain (1971-2005). Ann Occup Hyg. 2011;55:239-47. 22. Reid A, de Klerk NH, Ambrosini GL, Berry G, Musk AW. The risk of lung cancer with increasing time since ceasing exposure to asbestos and quitting smoking. Occup Environ Med. 2009;63:509-512.
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23. Markowitz SB, Levin SM. Miller A, Morabia A. Asbestos. asbestosis. smoking. and lung cancer. New findings from the North American insulator cohort. Am J Respir Crit Care Med.
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an
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2013;188:90-6.
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Table1. Selected characteristics of the case and control subjects Case subjects
Control subjects
(N=165)
(N=825)
Variable N
%
N
%
Female
35
21.2
650
21.2
Male
130
78.8
≤ 1937
54
32.7
270
32.7
1938-1947
65
39.4
325
39.4
1978-1969
46
27.9
230
27.9
43
26.1
317
38.4
31
18.8
158
19.2
91
55.1
350
42.4
31
19.1
227
28.3
43
26.5
236
29.4
88
54.4
339
42.3
60
36.4
391
47.4
105
63.6
434
52.6
2-15
52
31.5
339
41.1
16-30
96
58.2
397
48.1
≥ 31
17
10.3
89
10.8
us
an
Smoking (pack-year) No
M
1-20 ≥ 21
175
cr
Calendar year of birth (years)
ip t
Gender
78.8
ed
Cumulative exposure index (mg/m3 x years)a ≤ 10
pt
11-30
Branch other
Ac ce
≥ 31
asbestos-cement
Time since termination of employment (years)
Notes: N = number of patients; other = other types of plants a
No data for 3 cases and 23 controls
17 Page 17 of 20
Table 2. Odds ratios (ORs) for lung cancer among the former workers of asbestos processing plants ORa
95%CI
ORb
95%CI
No
1.00
1.00
1-20
1.50c
0.90-2.47
1.67
1.00-2.80
≥ 21
2.07c
1.36-3.15
2.23
≤ 10
1.00
11-30
1.35
0.82-2.23
1.38
0.83-2.29
≥ 31
2.09
1.31-3.34
1.99
1.22-3.25
Characteristic
1.45-3.46
cr
Cumulative exposure index (mg/m3 x years)d
ip t
Smoking (pack-year)
other
1.00
an
us
1.00
1.00
asbestos-cement plants
1.67
1.17-2.39
1.50
1.03-2.21
1.00
1.00
1.69
1.15-2.49
1.71
1.14-2.55
1.33
0.72-2.47
1.30
0.69-2.49
16-30
Ac ce
≥ 31
pt
2-15
ed
Time since termination of employment (years)
M
Branch
Notes: OR = odds ratio; CI = confidence interval; other = other types of plants a
Adjusted for pack-year
b
All variables were included in the multivariate model
c
Unadjusted
d
No data for 3 cases and 23 controls
18 Page 18 of 20
Table 3. Odds ratios (ORs) for lung cancer in the lower lobe among the former workers of asbestos processing plants Cases
Controls
ORa
95%CI
ORb
95%CI
1.00
(N=39)
(N=195)
No
11
91
1.00
1-20
6
40
1.24c
0.44-3.51
1.08
0.36-3.28
≥ 21
22
64
3.35c
1.43-7.83
3.22
1.31-7.89
≤ 10
3
46
1.00
11-30
6
59
1.49
us
Characteristic
≥ 31
29
87
5.06
other
15
83
asbestos-cement plants
24
112
cr
ip t
Smoking (pack-year)
Cumulative exposure index (mg/m3 x years)d
1.00
0.36-6.22
1.53
0.36-6.60
1.42-18.03
5.64
1.53-20.77
1.00
1.00
1.19
0.58-2.44
1.00
0.44-2.26
91
1.00
1.00
85
1.97
0.85-4.60
2.31
0.92-5.79
19
0.99
0.23-4.21
1.03
0.22-4.73
an
13
pt
2-15
23
Ac ce
16-30 ≥ 31
ed
Time since termination of employment (years)
M
Branch
3
Notes: OR = odds ratio; CI = confidence interval; other = other types of plants a
Adjusted for pack-year
b
All variables were included in the multivariate model
c
Unadjusted
d
No data for 1 cases and 3 controls
19 Page 19 of 20
Table 4. Odds ratios (ORs) for lung cancer in the upper and middle lobes among the former workers of asbestos processing plants Cases
Controls
ORa
95%CI
ORb
95%CI
1.00
(N=126)
(N=630)
No
32
226
1.00
1-20
25
118
1.54c
0.87-2.76
1.78
0.98-3.24
≥ 21
69
286
1.79c
1.11-2.90
2.03
1.22-3.36
≤ 10
28
181
1.00
11-30
37
177
1.33
us
Characteristic
≥ 31
59
252
1.65
other
45
308
asbestos-cement plants
81
322
cr
ip t
Smoking (pack-year)
1.00
0.78-2.28
1.34
0.77-2.33
0.98-2.79
1.48
0.85-2.58
1.00
1.00
1.85
1.23-2.80
1.73
1.11-2.70
248
1.00
1.00
312
1.60
1.02-2.49
1.60
1.01-2.52
14
70
1.37
0.69-2.74
1.31
0.63-2.71
an
pt
Cumulative exposure index (mg/m3 x years)d
2-15
39
≥ 31
73
Ac ce
16-30
ed
Time since termination of employment (years)
M
Branch
Notes: OR = odds ratio; CI = confidence interval; other = other types of plants a
Adjusted for pack-year
b
All variables were included in the multivariate model
c
Unadjusted
d
No data for 2 cases and 20 controls
20 Page 20 of 20