Incidence of Malignant Pleural Mesothelioma due to Environmental Asbestos Fiber Exposure in the Southeast of Turkey

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1 Clinical Investigations Respiration 2000;67: Received: November 26, 1999 Accepted after revision: June 27, 2000 Incidence of Malignant Pleural Mesothelioma due to Environmental Asbestos Fiber Exposure in the Southeast of Turkey A. Şenyiğit a C. Babayiğit a M. Gökirmak c F. Topçu a E. Asan a M. Coşkunsel a R. Işık a M. Ertem b a Department of Chest Diseases and b Department of Public Health, Faculty of Medicine, University of Dicle, Diyarbakır, c Department of Chest Diseases, Faculty of Medicine, University of İnönü, Malatya, Turkey For editorial comment see p Key Words Asbestos W Malignant pleural mesothelioma W Epidemiology Abstract Background: Inhabitants of the southeast of Turkey (ST) have been exposed since childhood to inhalation of asbestos, from a material containing tremolite, used for whitewashing. This has resulted in an increased incidence of malignant pleural mesothelioma (MPM). Objectives: To review the epidemiological features of MPM cases in ST; to calculate and compare the incidence with the previously reported ones. Subjects and Methods: The study included 176 MPM cases from different places in ST. The incidence of MPM was calculated for those places according to the distribution of the cases. Results: In the previously identified regions of asbestos (region 1) where the population had been informed of the danger with the soil some decades ago, the MPM incidence was decreased, as compared to the previous reports. The annual incidence of MPM in these places was found to be 42.9 per million in this study while it had been reported to be per million in the previous studies. In contrast, the incidence that was reported previously to be 2.75 per million in the regions where asbestos exposure had not been identified before (region 2) was found to be 8.6 per million in this study. In region 2 the incidence of MPM increased even in the second half of the last decade (5.9 versus 11.9 per million). Conclusions: Use of asbestos-containing soil continues in different places in ST. Even if the use of this soil is abandoned today, MPM will be an important health problem in this region till the third or fourth decades of this century. Informing the villagers of the danger and preventing the use of this soil may result in a considerable decrease in the incidence of MPM. Introduction Copyright 2000 S. Karger AG, Basel Malignant pleural mesothelioma (MPM) is an incurable disease which is almost exclusively due to inhalation of asbestos fibers [1, 2]. The disease is one of the major health problems in Turkey [3]. This is due to the many ABC Fax karger@karger.ch S. Karger AG, Basel /00/ $17.50/0 Accessible online at: Abdurrahman Şenyigit Tıp Fakültesi Göğüs Hastalıkları, Diyarbakır (Turkey) Tel /4287 or 4270, Fax senyigit@dicle.edu.tr

2 asbestos deposits which exist in some rural parts of central and eastern Anatolia [3 5]. The people living in the southeast of Turkey (ST) were also reported to have a high incidence of MPM due to environmental asbestos exposure [6, 7]. The material containing asbestos is quarried from the mountains by the male population both for local use and for sale elsewhere. It is used as a whitewash for the walls and floors of the houses. The application is usually done by women who grind the material to powder and suspend it in water. The process is repeated each year. Consequently householders are repeatedly exposed from an early age [4, 6]. There is a large variation in the incidence of mesothelioma in different countries and in most places a steadily rising number of cases with time [2]. The studies investigating the incidence of MPM in Turkey are little in number, and most of them report the rates of disease in small places like villages [8 16]. This study analyzing a large series of MPM patients is the first one to investigate the incidence of MPM in most places in ST and to compare the results with the previously reported ones in order to detect the changes in incidence. The objectives of the present study were: (i) to identify all new cases of MPM diagnosed in ST over a specified period ( ) with a view to estimating incidence; (ii) to compare the calculated incidence with previously reported rates from the same region, and (iii) to describe some features of MPM patients, including age, sex, and association with asbestos exposure. Subjects and Methods This study is designed to investigate the incidence of MPM in ST. The patients who were diagnosed to have mesothelioma in a reference university hospital between the years 1990 and 1999 are included in the study. Mesotheliomas are only accepted in the register if they are based on histological or cytological examinations. The pathological diagnosis is made on the basis of ordinary tissue sections stained with hematoxylin-eosin; further immunohistochemical stains are used as needed. The information about the patients including age, sex and birthplace were extracted from the records. The history of occupational or environmental exposure to mineral fibers or chemicals was analyzed carefully. Asbestos exposure was noted as positive for patients from places where environmental asbestos was known to exist. A number of patients came from places where environmental asbestos had not been reported previously. These areas were referred to as region 1, while the areas where asbestos exposure was not identified before were named as region 2. Soil samples from different places in region 2 were investigated by electron microscopy. The data for populations living in areas of interest could only be taken for the years 1990 and 1997 from the State Institute of Statistics. Then, the annual population figures were calculated for each Fig. 1. The age distribution of 176 MPM patients. year for the period covered by the study by using the annual rate of increase in population in these areas. The incidence calculated using these population figures was compared with the rates reported in previous studies. Results One hundred (57%) of the 176 patients were men and 76 (43%) were women, giving a male/female ratio of 1.3/1. The ages of female and male patients ranged from 21 to 79 (mean 54.2) and from 25 to 77 (mean 52.4) years, respectively. The age distribution of cases is shown in figure 1. Thirteen percent of the patients were diagnosed as MPM by cytological examination of the pleural fluid, while histopathological examination of pleural biopsies or lymph nodes (1 case) revealed the diagnosis in 83% of the cases. There was a positive history of asbestos exposure in 60% of cases. Analysis of soil samples from all places of region 2 by electron microscopy showed both serpentine (little in amount) and amphibole (tremolite) type asbestos fibers in only 4 of them. When the patients coming from the recently identified four places with asbestos exposure in region 2 were also considered, the overall ratio of the patients with a history of asbestos exposure increased to 68%. The distribution of the patients according to the history of asbestos exposure is seen in table 1. As is seen in this table, none of the cases had occupational or industrial exposure to asbestos. The regional distribution of the patients and the calculated incidence for the first and second half of the last decade are shown in table 2. The incidence of MPM was found to be 42.9 and 8.6 per million in regions 1 and 2, Mesothelioma due to Environmental Asbestos Exposure Respiration 2000;67:

3 Table 1. The distribution of patients according to the history of asbestos exposure Asbestos exposure Male (n = 100) Female (n = 76) Evironmental Occupational 0 0 Industrial 0 0 None Represents all cases from region 1 and the recently identified four places with asbestos exposure in region 2. Table 2. The regional distribution of the patients and incidence of MPM per million population of towns/cities in ST City or town in Turkey Cases per 1,000,000 inhabitants * * * Previously identified areas of asbestos (region 1) Maden (n = 19) Ergani (n = 39) Çüngüş (n = 6) Çermik (n = 18) Siverek (n = 23) Total (n = 105) 47.2 a 37.5 a 42.9 a Areas where asbestos was not identified before (region 2) Dicle (n = 14) Mardin (n = 10) Silvan (n = 5) Batman (n = 8) Elazığ (n = 10) (excluding Maden) Şanlıurfa (n = 8) (excluding Siverek) Others** (n = 16) Total (n = 71) 5.9 b 11.9 b 8.6 b Incidence in total population in these places. Diyarbakır (excluding Çermik, Çüngüş, Ergani, Dicle, Silvan), Bingöl, Adıyaman, Şırnak, Siirt, Bitlis, Muş. a b respectively. The incidence of MPM in ST was calculated to be 22.8 per million. As shown in table 2, the incidence of the disease increased considerably in region 2 between the years 1990 and The increase in incidence was even greater in the second half of this decade when compared to the first half (5.9 versus 11.9 per million). Fig. 2. The changes in incidence of MPM in region 1 and region 2. [The data for are from ref. 17.] The changes in incidence of MPM according to the results of this and a previous study are shown in figure 2 [17]. Also asbestos outcrops and patient birthplaces are precisely plotted on a map showing the ST, in figure 3. Discussion This study shows that the risk of pleural mesothelioma is increasing in some parts of ST. The decrease in incidence of MPM in region 1 is mostly due to awareness of the people living there of the danger related to this soil and the resultant decrease in usage of it. The high sex prevalence for males in most countries is strong evidence for occupational exposure to asbestos, since females are less likely to have worked in contaminated areas [18 21]. The calculated male/female ratio, however, is 1.3 in this study. There are two reasons that explain the higher prevalence of MPM in females in Turkey compared to other countries. One reason is the wider use of asbestos-containing soil by women although the men are the ones who dig and transport the mineral. Secondly, although women usually cover their mouths and noses during whitewashing, they are still the ones predominantly engaged in household tasks. In industrialized countries where asbestos was widely used from the end of World War II until the end of the 1970s, the incidence per year of mesothelioma is presently 2 per million in females and per million in males. Geographical variations in incidence are due to regional differences in industrial activity. Regions with 612 Respiration 2000;67: Şenyiğit/Babayiğit/Gökirmak/Topçu/Asan/ Coşkunsel/Işık/Ertem

4 Fig. 3. Map showing the ST and asbestos outcrops (n represents the number of cases who were born in that place). shipyards are particularly at high risk. In the USA, the highest published annual rate per million is 13.3 for males and 2.5 for females and in Australia the rates are 66 per million for males and 7 per million for females [21]. According to the results of this study the incidence of MPM in seven areas of Turkey is higher than that of the USA, which is an industrialized country. The incidence found in one of the towns investigated (Maden) was also higher than the rates found in Australia. Asbestos is not used in industry in ST except for a pipe factory. And also, none of the patients with MPM worked in this factory or lived near it. So, none of the patients was shown to have an occupational exposure. In the five previously known areas, the digging and use of asbestos-containing soil has almost completely ended. However, in the four newly recognized places (shown on the map) people still dig and use this soil. Dicle, in which the incidence of MPM was found to be 35.9 per million (the fourth highest incidence), is one of those newly detected places. Since the incidence of disease was found to be increased in region 2 compared to the previous studies, and since this increase was even greater in the second half of the last decade compared to the first half, MPM will probably continue to be an important health problem of the region. This is due to the long latency period of mesothelioma which can explain a rise in the incidence of disease for up to years after the application of strict laws on the use of this mineral fiber. In the present study, changes in the incidence of MPM in ST since 1976 were also investigated. Although the incidence of disease was found to be very high in region 1 (42.9 per million) compared to region 2 (8.6 per million), this was still lower than in previous studies reporting an incidence of per million for region 1 [17]. Asbestoscontaining soil is still being used in some villages and towns where the danger is not known, while in region 1 this soil has not been used for a long time, since the disease was first noticed there and in fact was called as Çermik s Disease in the region. This illustrates how important it is to detect the asbestos and inform the villagers of the danger. Since the exposure is due to whitewashing of the houses, the risk will considerably decrease if this pro- Mesothelioma due to Environmental Asbestos Exposure Respiration 2000;67:

5 cedure is stopped. When the long latency period is considered, however, the risk will even continue until the second decade of this century, since the use of the soil was stopped in the early 1980s. In addition, the calculated incidence of MPM may be less than the real incidence of the disease in ST, because many districts of the region are underserved by health services and the diagnosis of MPM is not likely to be made clinically. There might also be some patients with suspected MPM who could not be diagnosed by closed pleural biopsy and rejected the more invasive diagnostic procedures. In addition, these places are the most prevalent ones from which people migrate to the big cities. Another factor influencing incidence is the type of fiber used, the incidence being higher with crocidolite and amosite than with chrysotile [21]. Tremolite appears, dose for dose, to be more carcinogenic than chrysotile, but it is regarded by Churg as a low-grade carcinogen [22]. Since the exposed fiber in this study and the previous studies from Turkey was tremolite [6, 8], this fiber should also be considered as a very important carcinogen. The importance of tremolite has been underlined by McDonald et al. [22]. These authors felt that the tremolite contaminating many industrial minerals, including chrysotile, probably explained most of the cases in the Quebec mining region and perhaps up to 20% of cases elsewhere [22]. As is seen in figure 3, the newly detected regions of asbestos are in the neighborhood of the previously known regions and the whole region seems to be on a fault line. The asbestos fibers found in many neighbor countries of Turkey are also tremolite [2]. As a conclusion, this study reveals the extent of MPM in ST and gives support to public health concern for more stringent environmental control of this fiber. The decrease in the incidence of disease in region 1 is thought to be primarily due to informing the villagers of the danger. 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