Document aBnwLMex2JMwvoy8md9j21e3y

ORIGINAL PAPERS International Journal of Occupational Medicine and Environmental Health, 2005;18(4):313 -326 MORTALITY FROM MALIGNANT NEOPLASMS AMONG WORKERS OF AN ASBESTOS PROCESSING PLANT IN POLAND: RESULTS OF PROLONGED OBSERVATION URSZULA WILCZYNSKA, WIESLAW SZYMCZAK, and NEONILA SZESZENIA-D^BROWSKA Department of Environmental Epidemiology Nofer Institute of Occupational Medicine Lodz, Poland Abstract Objectives: The study on mortality from cancer among workers of an asbestos plant manufacturing asbestos yarn, cloth, cords, packings, stuffing, brake linings and asbestos-rubber sheets was launched in the 1980s. The present paper discusses the results of further tracing of asbestos workers of the same plant. Materials and Methods: The study cohort covered 4497 workers employed at the asbestos plant in 1945-1980. The follow-up of the cohort continued until 31 December 1999. Deaths by causes were analyzed using standardized mortality ratio (SMR) calculated by the person-years method. The mortality pattern of the general population of Poland was used as reference. Results: The availability of the cohort was 93.1% (2805 men and 1382 women were traced). Mortality from malignant neoplasms in total (281 deaths among men, SMR = 118, 95%CI: 105-133 and 135 deaths among women, SMR = 159, 95%CI: 133-188) as well as that from lung cancer (102 deaths among men, SMR = 126, 95%CI: 103-153 and 18 deaths among women, SMR = 259, 95%CI: 153-409) were significantly higher than in the general population. Unlike earlier stages of analysis, the present study revealed an increased risk of pleural mesothelioma (2 deaths among men, SMR = 510, 95%CI: 62-1842 and 3 deaths among women, SMR = 2033, 95%CI: 419-5941). Mortality analysis among workers with asbestosis and in those without diagnosed asbestosis, did not reveal direct association between the risk of asbestos-induced lung cancer and previously diagnosed asbestosis. Conclusions: The prolonged cohort tracing showed an increased risk of asbestos-related cancers. It concerned mainly workers hired by the plant between 1945-1955, when the working condition were most strenuous. Key words: Asbestos, Cohort study, Lung cancer, Mortality, Pleural mesothelioma, Smoking INTRODUCTION The study on mortality from cancer among workers of the asbestos plant manufacturing asbestos yarn, cloth, cords, packings, stuffing, brake linings, and asbestos-natural rub ber sheets was launched in the 1980s. In view of the project specificity, namely the cohort definition, tracing time and long latency period of asbestos-induced cancers, which for mesotheliomas can be of more than 30 years, the previous stages of the study could not yield a comprehensive assess ment of cancer risk in this cohort. The present paper dis cusses the results of further tracing of an enlarged initial cohort of asbestos workers of the same plant. MATERIALS AND METHODS The cohort comprised all workers employed at the study plant for at least three months and hired within the pe riod of 1945-1980. This period can be divided into three Received: October 19, 2004. Accepted: August 17, 2005. Address reprint requests to Dr. U. Wilczynska, Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, sw. Teresy 8, 91-348 Lodz (e-mail: wies@imp.lodz.pl). IJOMEH 2005;18(4) 313 ORIGINAL PAPERS 0. WILCZYNSKA, ET AL. intervals: from 1945 to 1955, from 1956 to 1973, and from 1974-1980. The first interval marks the period when the working conditions in the plant were most strenuous. In 1956, the plant was thoroughly modernized due to install ing a ventilation system. Accordingly, the workers who were employed in 1956 or later were exposed to lower levels of asbestos dust than those who joined the plant before that year. The workers employed during the first two intervals were the subject to cohort tracing at the two earlier stages of the project [1-4]. The present stage in cludes the observation of the cohort enlarged by including workers who joined the plant workforce in the period of 1974-1980. The cohort was traced until 31 December 1999. For the deceased workers, the date and place of death were re corded and then verified against the documentation col lected from different sources to ascertain the cause of death given in the death certificate. The latter was coded according to the International Classification of Diseases, Injuries and Causes of Death (ICD-9). The analysis of deaths by causes was based on standardized mortality ratios calculated using the person-years method [5]. The reference group was the general population of Po land, including the data on deaths by causes, gender and age during 1945-1999. The person-years for the cohort members were calculated for the period between start ing the employment and "exit" from the cohort because of death or reaching the age of 80 years. The remaining cohort members had their person-years calculated until 31 December 1999, when the tracing was terminated. The 95% confidence intervals (CI) for SMRs were calculated by applying Poisson distribution, with the use of the PYRS software provided by the International Agency for Re search on Cancer (IARC) [6]. Separate analysis was made for male and female workers. Based on the employment data at the asbestos plant, sub cohorts by exposure duration were distinguished. The ex posed workers were those working at the production and auxiliary departments and the non-exposed were adminis tration workers. Additional analysis was made for workers at particular departments and those with diagnosed/nondiagnosed asbestosis. For mortality analysis, the data on the smoking habit were also collected. This information derived from the medical records of prophylactic examinations and con sultations conducted by the Out-patient Clinic of Oc cupational Diseases, Nofer Institute of Occupational Medicine, Lodz. Each cohort member reporting for such an examination was interviewed whether he or she had been smoking at least one cigarette a day for a period of more than three months. The findings made it possible to estimate the proportion of smokers in the study popula tion and then to assess lung cancer risk with the use of Axelson's correction for the control of the tobacco smok ing parameter [7,8]. RESULTS The cohort tracing concerned 4497 workers (3027 males and 1470 females) employed at the asbestos plant for at least three months within the period of 1945-1980. Life status was established for 4187 workers (2805 males and 1382 females). Thus, the availability of the cohort was 93.1%; 1854 deaths of workers aged below 80 years were recorded and 91.7% of cases had their cause of death as certained (Table 1). The cohort characteristics, by selected parameters, is summarized in Table 2. Most (55.2%) of the cohort mem bers had their history of work in the plant shorter than five years. The percentage of workers with such a short period of employment was higher among male (60.7%) than female (41.5%) workers. In the cohort, the majority (72.6%) of workers were below 40 years of age at starting their work at the plant. Almost 50% of workers were in volved in the production of insulation materials (20.6%), asbestos yarn and cloth (17.9%) and friction materials (7.9%). Over 50% of workers were employed at auxiliary (mechanical, electricity, maintenance and repair works) and administration departments (Table 2). A total of 371 workers in the cohort (8.9%) had asbestosis diagnosed as an occupational disease. The smoking status was determined for 1096 (26.2%) workers. Generally speaking, almost two third of the sub cohort smoked or used to smoke cigarettes. The propor- 314 IJOMEH 2005;18(4) Table 4. M ortality from malignant neoplasms (obs., SMR and 95%CI) by plant departments in the male subcohort o f workers exposed to asbestos dust Abbreviations as in Table 3. CANCER MORTALIY AMONG ASBESTOS WORKERS ORIGINAL PAPERS GO ^ Ox -d- GO Ox CO TO 4p TO GO To Ox TO TO CO TO 0-4 0-4 CO 0-4 CO 0-4 CO TO CO to Ox ^ Ox 0-4 GO I CO 0-4 CO ^ TO p4 Ox 0-4 to p4 TO ^ ^ i 0-4 0-4 Ox GO -d^ 0-4 to GO GO TO 0-4 I CO 04 04 I 0-4 0-4 p4 Ox 0-4 0-4 TO' 0-4 -^1- 1 CJ o' I . ^c CJ O --| 03 .P O u 3 O 3S g U2 m 3 2 m GT IJOMEH 2005;18(4) 317 ORIGINAL PAPERS 0. WILCZYNSKA, ET AL. latter of pancreas cancer (6 deaths, SMR = 116, 95%CI: 226-1341) and pleural mesothelioma (2 deaths, SMR = 932, 95%CI: 113-3367). The risk of lung cancer was found to concern all the plant departments, but the SMR values ranging from 117 (for 52 deaths) to 156 (for 19 deaths) did not reach the level of statistical significance (Table 4). The analysis by duration of employment under exposure revealed excess mortality from the same causes as those found for the whole cohort, but statistically significant findings for total cancers and lung cancer applied only to the workers with exposure below five years (155 deaths, SMR = 125, 95%CI: 106-146 and 59 deaths, SMR = 140, 95%CI: 107-181, respectively). In the group working for more than five years, the risk of death from these two causes was also increased, but its level was not statistically significant (SMR = 110 and 111, respectively). In all the groups classified by exposure duration, one case of pleural mesothelioma was recorded, which indicated about a five fold increase, but death risk was not statistically significant compared to the level observed in the general population (Table 5). Mortality analysis with respect to the year of employment revealed that the highest risk of death from asbestos-related cancer concerned the workers hired by the plant between 1945 and 1955. They were characterized by significant excess mortality from cancer (117 deaths, SMR = 139, 95%CI: 115-167), including lung cancer (42 deaths, SMR = 155, 95%CI: 112-210) and pleural meso thelioma (2 deaths, SMR = 1587, 95%CI: 192-5733). In workers employed in a later period of the plant's activity, the number of cancer deaths only slightly exceeded that in the general population (Table 6). Mortality in the female cohort Under the period of cohort tracing, 435 deaths cases were recorded among female workers compared to the expect ed 320.9 (SMR = 136, 95%CI: 124-149), which indicates a significantly higher mortality in the cohort than in the reference population. The main causes of this high mor tality were malignant neoplasms (135 deaths, SMR = 159, 95%CI: 133-188), including gallbladder cancer (10 deaths, SMR = 257, 95%CI: 123-473), lung cancer (18 deaths, SMR = 259, 95%CI: 153-409), pleural mesothelioma (3 deaths, SMR = 2033, 95%CI: 419-5941), and cervical cancer (13 deaths, SMR = 196, 95%CI: 104-335) (Table 7). Significant excess mortality from cancer was mostly found among female workers exposed to asbestos dust. This finding referred to total cancer cases (124 deaths, SMR = 162, 95%CI: 135-193), gallbladder cancer (9 deaths, Table 5. Mortality from selected causes by duration of employment in the male subcohort of asbestos workers Cause of death (coded according to ICD-9) All causes (001-999) Malignant neoplasms (140-208) Lung (162) Pleura (163) Abbreviations as in Table 3. Obs. 894 155 59 1 < 5 years SMR 167 125 140 476 95%CI 156-178 106-146 107-181 Obs. 525 126 43 1 > 5 years SMR 107 110 111 556 95%CI 98-117 92-131 80-150 Table 6. Mortality from selected causes by the year of starting employment in the plant in the male subcohort of asbestos workers Cause of death (coded according to ICD-9) All causes (001-999) Malignant neoplasms (140-208) Lung (162) Pleura (163) Abbreviations as in Table 3. Obs. 468 117 42 2 1945-1955 SMR 125 139 155 1587 95%CI 114-137 115-167 112-210 192-5733 Obs. 779 142 52 - 1956-1973 SMR 140 106 112 0 95%CI 130-150 89-125 84-147 Obs. 172 22 8 - 1974-1980 SMR 182 105 110 0 95%CI 156-211 66-159 47-217 318 IJOMEH 2005;18(4) CANCER MORTALIY AMONG ASBESTOS WORKERS ORIGINAL PAPERS Table 9. Mortality from selected causes: by duration of employment in the female subcohort of asbestos workers Cause of death (coded according to ICD-9) All causes (001-999) Malignant neoplasms (140-208) Lung (162) Pleura (163) Abbreviations as in Table 3. Obs. 193 57 8 1 < 5 years SMR 158 178 311 1667 95%CI 136-182 135-231 134-613 Obs. 242 78 10 2 > 5 years SMR 122 147 228 2222 95%CI 107-138 116-183 109-419 269-8027 Table 10. Mortality from selected causes by the year of starting employment in the plant in the female subcohort of asbestos workers Cause of death (coded according to ICD-9) Obs. 1945-1955 SMR 95%CI Obs. 1956-1973 SMR 95%CI Obs. 1974-1980 SMR 95%CI All causes (001-999) Malignant neoplasms (140-208) Lung (162) Pleura (163) Abbreviations as in Table 3. 193 145 125-167 195 115 99-132 59 184 140-237 57 120 91-155 8 332 143-654 5 123 40-287 2 3782 458-13 662 1 1250 47 267 196-355 19 338 203-528 5 1014 329-2366 -0 SMR = 256, 95%CI: 117-486), lung cancer (13 deaths, SMR = 209, 95%CI: 111-357), and pleural mesothelioma (3 deaths, SMR = 2267, 95%CI: 468-6625). The site of cancer, for which an increased risk could be found re gardless of asbestos exposure was the lung. Among the exposed workers, the risk of lung cancer was doubled (13 deaths, SMR = 209, 95%CI: 111-357) and in the non-exposed population, six times higher (5 deaths, SMR = 678, 95%CI: 220-1582) compared with the reference popula tion (Table 7). An analysis by departments revealed in general an in creased cancer risk for all the departments and significantly increased for asbestos yarn and cloth production (43 deaths, SMR = 159, 95%CI: 115-214) and auxiliary departments (39 deaths, SMR = 200, 95%CI: 142-273). An analysis by cancer site indicated a significant excess mortality from liver cancer in women working in the asbestos yarn and cloth production (5 deaths, SMR = 327, 95%CI: 106-763), pleural mesothelioma in those involved in the production of friction (1 case, SMR = 20024, p < 0.01) and insulation materials (2 cases, SMR = 4218, 95%CI: 511-15237), and ovarian cancer in women employed in the department of asbestos yarn and cloth production (6 deaths, SMR = 376, 95%CI: 138-818). In the departments under study, a non significant increase in the number of lung cancer cases among workers could be noted (Table 8). A significant excess in general mortality and that from ma lignant neoplasms, including lung cancer, was found in the workers with both short and long period of employment un der exposure. Among workers with a short exposure dura tion, the risk of lung cancer was found to be about three times higher (8 deaths, SMR = 311, 95%CI: 134-613) than in the reference population, while in those exposed for a longer pe riod, this risk was more than twice as high (10 deaths, SMR = 228, 95%CI: 109-419). The latter group was also character ized by a significantly increased risk of pleural mesothelioma (2 deaths, SMR = 2222, 95%CI: 269-8027) (Table 9). SMRs calculated for subcohorts distinguished by the year of employment pointed to a significant excess of all cancer cases (59 deaths, SMR = 184, 95%CI: 140-237), lung can cer (8 deaths, SMR = 332, 95%CI: 143-654) and pleural mesothelioma cases (2 deaths, SMR = 3782, 95%CI: 458 13662) among female workers hired by the plant between 1945 and 1955. However, the excess in all cancer cases and lung cancer in particular appeared to be still higher for workers who began their employment in 1974-1980 (19 deaths, SMR = 338, 95%CI: 203-528 and 5 deaths, SMR = 1014, 95%CI: 329-2366, respectively) (Table 10). IJOMEH 2005;18(4) 321 ORIGINAL PAPERS 0. WILCZYNSKA, ET AL. workers, while in the general population a reverse tenden cy can be noted: lung cancer risk among males was found to be six times higher than in females. This result of our study would thus indicate that women may be more sensi tive to asbestos dust than men. Similar unfavorable result obtained in the females for pleural mesothelioma can be explained by different anatomic (e.g., body size) and physi ologic (e.g., breathing mode) characteristics between male and female patients. The female characteristics enhances asbestos fiber retention in the lungs and facilitates cancer development [12]. The increased risk of lung cancer was noted in the workers at all the departments under study, but it was not statisti cally significant. As revealed in the analysis by exposure duration, the ex cess risk of lung cancer applied to male workers employed for less than 5 years. In the female cohort the risk of lung cancer was increased, regardless of exposure duration. This finding also concerned the general and cancer-relat ed mortality. One may expect that in the group of workers with a short duration of employment, the effects of other undefined occupational exposures at previous workplaces will become evident. This group may also be characterized by a larger number of hazardous lifestyle factors than the workers with longer employment. These aspects may affect the results of an analysis that takes account of the asbestosis diagnosed in the cohort. The views on a possible association between asbestosis and the risk of lung cancer in workers exposed to asbestos dust vary among the researchers [13-22]. In the study co hort, an excess mortality from lung cancer could be noted in both groups of workers with and without diagnosed asbestosis. Moreover, a statistically significant risk of lung cancer was found only in the group of workers without asbestosis. This might be due to the confounding variable of "employment duration" since the workers with asbestosis naturally worked for a longer period under exposure. One should add that the absence of a significant lung cancer risk in the asbestosis-affected population, which seems contradictory to the findings of other cohort studies on workers with asbestosis [13-24], is actually far from being realistic. In other studies, the cohort tracing started from the date of diagnosed asbestosis, while in the present pro ject it started from the date of the worker's employment in the asbestos plant. The problem of tobacco smoking as a factor modifying the risk of lung cancer has been investigated from the begin ning of the cause-effect epidemiological studies on popula tions exposed to asbestos dust [25-27]. The outcomes of numerous analyses have definitely confirmed that smoking contributes to an increased risk of lung cancer. However, it remains to be investigated whether the combined effect of both causal agents: smoking and asbestos dust, is of addi tive or multiplicative nature [28-38]. Since it was extremely difficult to obtain individual data on the smoking habit in the retrospective cohort, which is a common methodologi cal obstacle, we decided to apply Axelson's correction [7,8] that makes it possible to assess lung cancer risk once the impact of tobacco smoking is eliminated. For this purpose we used, medical records of prophylactic examinations and medical consultations of asbestos plant workers who were referred to the Nofer Institute of Occupational Medicine for check-ups. Like in other studies on asbestos dust ex posure, current and ex-smokers prevailed in the cohort [8,39-41], making 84.2% of the male and 39.6% of the female populations. The respective values for the general population of Poland are 75.0% and 39.6%. Considering that the percentage of smoking women in the study cohort and in the general population was the same, Axelson's cor rection did not affect the risk of death from lung cancer (SMRcor = SMR = 259). The proportion of male smok ers in the study cohort was significantly higher than in the general population of Poland (84.2% vs. 75.0%) and after applying Axelson's correction (SMRcor = 114) it points to a statistically insignificant increase in the risk of lung can cer development. However, considering the proven syn ergistic effect of tobacco smoking and asbestos exposure, we are aware that the corrected value does not reflect the risk in the real carcinogen-exposed population. The value of the true risk of cancer development in the male cohort was SMR = 126. Unlike the earlier stages of the analysis, the present study revealed a significantly increased risk for pleural mesothe lioma that is specific for asbestos exposure. The increased 324 IJOMEH 2005;18(4) CANCER MORTALIY AMONG ASBESTOS WORKERS ORIGINAL PAPERS incidence of mesothelioma could be detected only as late as at this stage of our study because of very long latency period of this neoplasm. Prolonged observation of the cohort revealed five cases of this cancer, with an average latency period of more than 39 years. In other cohort studies on workers exposed to asbestos dust, excess mortality from other cancer sites [28,42-44] could also be noted. In the female population this find ing applied to gallbladder, cervical and breast cancers, and in men to gallbladder and large intestine cancers. The in creased risk for large intestine cancer is consistent with the outcomes of the meta-analysis [45] concerning 31 reports on workers' exposure to asbestos dust. The results of the present prolonged cohort tracing of as bestos workers revealed a significant health hazard from exposure, manifested by an increased risk of lung cancer and pleural mesothelioma. This refers particularly to fe male workers for whom the mortality ratio was found to be 2.5 times as high as for the female general population. 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