Document dQyq70Jw8o4VeMg4v4qgDYkaB

07019901 Environmental asbestos exposure and mesothelioma Marta R. Orenstein, MSc, and Marc B. Schenker, MD, MPH Epidemiologic studies of mesothelioma have focused primarily on occupational exposures to asbestos. Nonoccupational exposure to asbestos can be grouped into three main cate gories; paraoccupalional (familial), neighborhood, and true environmental exposures. Elevated mesothelioma rates not attributable to occupational exposures have been observed in asbestos mining and manufacturing areas. Asbestos is one of the most dangerous environmental carcinogens because of the small dose known to cause mesothelioma and the rapid lethality of the disease once it develops. Further research is needed to characterize the contribution and risk profile for environmental asbestos and mesothelioma, and for the devel opment of public health policy. On Opwi Pulm Mod 2000.637W77 C 2000 Lippincou WStiinns & Wilkins, Inc. Department of epidemiology a Preventive Medcine, School o( Medicine, University of California, Davis, California, USA. Conetpondence to Marc Schenher. MD, Department of Epidemiology Preventive Medicine. One Shield* Avenue, TB108, University of California, Davie, Davtt, CA 95616-8636; e-no achenhenSepm.ucUavit.edu Current Opinion In Pulmonary Medicine 2000,6:371-377 ISSN 1070-5287 C- 2000 Lippincott Wiliams & WiWns, Inc. Mesothelioma ' Mesothelioma is a rare cancer that primarily affects the pleura and peritoneum--the linings of the lungs and abdominal cavity, respectively. In the United States, 2000 to 3000 new cases of mesothelioma arc reported each year [1], Although mesothelioma is rare, the social impact of this disease is devastating because there is no satisfactory clinical treatment, and the survival time after diagnosis is typically less than 18 months [2-4]. Mesothelioma occurs in the substantial majority of cases as a result of asbestos exposure in occupational and environmental settings, although mesotheliomas from ocher exposures have been recognized [5,6]. Inhaled fibers that pass through the alveoli migrate to the pleura of the lungs, where they affect the mcsothclia! cells, thereby producing mesothelioma. Mesothelioma may also occur in the peritoneum of (he abdomen, or even more rarely, the pericardium of the heart. Risk is Strongly related to the intensity of asbestos exposure and to latency, so a very short period of exposure may bc followcd decades later by the sudden onset of malig nancy' and death. Tire latency period has a wide range, from a minimum of about 5 years |7] to a maximum of 72 years, so those exposed arc at risk all their lives [8], Children appear to be especially susceptible to even short periods of asbestos exposure and typically develop the disease at ages 45 to 50, whereas those'exposed after age 20 most often develop the disease at age 60 to 70. Kxposed women have been reported to develop pleural mesothelioma at rates at least as high as men with die. same exposures, although their overall numbers are much lower since fewer w omen have occupational expo sures |9], Of greatest concern with regard to environ mental asbestos exposure is the recognition that smaller, nonfrbrogenic doses of asbestos are adequate to cause mesothelioma. Asbestos Asbestos is the name given collectively to the fibrous forms of several naturally occurring silicate minerals that form under high pressure in the earth's crust and are commonly found around earthquake faults. Geologists divide asbestos into two categories, which differ in both structure and chemical composition: (1) serpentine, of which chrysotile is the only asbestiform type, and (2) amphibotes, which includes crncidolitc, amosite, anthophyllice, and the fibrous forms of actinolire and tremolite. 371 07019301 372 Neoplasm* of the lung Although most investigators agree that amphibole been on the rise [2.20] and is expected to reach its peak in asbestos is more potent in causing mesothelioma, there is ZOOG in the United States [1| and around 2020 in Europe still debate as to whether all mesotheliomas are caused by [21,22**] (Table 1). This trend reflects the average 25- to amphiboles (by themselves or as contamination of 40-year latency period between asbestos exposure and chrysodle asbestos), or whether chrysotile alone can cause disease presentation while taking into account (he slow mesothelioma. The amphibole hypothesis suggests that decline ofasbestos usage after World War 11(1,23]. mesothelioma is caused primarily by the amphibole species of asbestos. This is supported by lung burden Exact estimates of mesothelioma attributable to asbestos studies, which have demonstrated that amphiboles accu exposure vary from 60 to 88% of all eases [20,24,25j. mulate to a much greater degree in lung tissue, including Identifying prior asbestos exposure in mesothelioma cases of malignancy, despite the (act that chrysotile is the cases may he particularly difficult i>ccause small amounts predominating type of asbestos [3,10-12]. McDonald el of asbestos cxpnsure many decades before the disease al. (13] have found that amphibole fibers, including onset can result in malignancy. 'Hie estimated prevalence tremolicc, arc also more likely than chrysotile fibers to of prior asbestos exposure may in part vary with how cause fibrogcnic changes in the lung. Stanton er at. (14] intensively such a history is sought. However, there is no postulated that fibers with large aspect ratios (the ratio of question that the substantial majority ofcases arc attribut length to width) are most responsible for the carcinogenic able to prior asbestos exposure. effects of asbestos. Given larger aspect ratios for amphi bole species, this theory lends credence to the idea that Few studies have delved deeply into the question of amphibole asbestos is the most toxic. whether naturally occurring environmental asbestos poses any significant threat to the health of those living near such Other researchers have concluded that chrysotile is an deposits. Epidemiologic studies of mesothelioma have equally potent carcinogen with regard to mesothelioma focused primarily on occupational exposures to asbestos (rg, 115-17]. Lung burden studies that analyzed asbestos asbestos miners, railway and construction workers, brake content in the pleura (as opposed to lung tissue) have mechanics, building maintenance workers) [26-28]. yielded greater amounts of chrysotile in mesothelioma Although these studies have yielded a great deal of impor eases. Because mesothelioma is a cancer of the lung tant information, there are many ways in which environ pleura, this would seem to support this view. Chrysotile mental exposures arc likely to differ from occupational fibers are cleared more rapidly from the body than exposures, and little is known about the occurrence and asbestos fibers, and it is conceivable that they may "hit- risk factors for mesothelioma from environmental asbestos and-run," initiating disease before they arc cleared 11R(. exposure. Occupational exposure to asbestos is generally much greater in concentration and occurs at different ages Although the matter remains unresolved, most natural than environmental exposure. Environmental exposures chrysorile deposits arc contaminated with amphiboles, clouding the issue for exposed populations. Occupational and environmental asbestos exposure Table 1 Incidence of mortaltty of mesothelioma In various counties and areas over time (per mltton inhabitants per year) Country or area Year Male Female The association between asbestos exposure and mesothelioma was first demonstrated in I960 by Wagner rial. [19]. Mesotheliomas of the pleura were observed in people living or working in a crocidolite mining region in South Africa. Ten of the 33 patients with mesothe lioma were bom in the vicinity of the mines and had no occupational asbestos exposure. Many patients had reported exposure to asbestos dust as a child. Although occupational exposures constituted (he majority' of the eases, the report suggests that childhood exposure ro asbestos was a cause of several eases. It is not possible to definitively separate occupational from familial or envi ronmental asbestos exposure in this case scries. Current rates of mesothelioma worldwide mirror raw asbestos consumption, and there Is general agreement that occupational asbestos exposure accounts for the majority of United Stales North America Nantes-Saint-Nazarv, Franca Texas Selected cities. United States United Slates Barcelona, Spain Great Britain Roland Great Britain Nanles-Safrit-Nazare, France United Kingdom Denmark Nantes-Saint-Nazarc Great Britain Australia Great Britain Great Britain Australia 1868-81 1972 1866-74 1876-80 1870s 1986 1963-80 1968-71 1980-84 1872-76 1875-84 1888 1978-80 1985-92 1868-71 1982-8B 1982-86 1887-81 1984 2.1 2.6 5.2 5.8 4.4-11.1 7.0-13.0 63 8.4 10.0 12.6 17.2 173 14,7 19.4 20.7 283 30.5 44.0 49.9 0.8 0,7 0.2 2.1 13-33 1.0-2.0 4.7 23 2.9 23 0.6 3.2 73 4.0 43 33 4.8 6/4 43 mesothelioma eases. The incidence of mesothelioma has PubBtfoed with permission [22"1, 07019901 Environmental asbestos exposure and mesothelioma Oranstein and Schenker 373 may begin at u younger age and continue for a longer dura tion than the normal working lifetime. Nonoccuparional exposure to asbestos can be grouped into three main cate gories: paraoccupationa! (familial), neighborhood, and true environmental exposures. Paraoccupatlonal (familial) exposure In close association with occupational exposures are those of spouses and children of exposed workers, These family members breathe asbestos dust brought home on the worker's clothing. These have been called "familiar or "domestic" exposures, and have been clas sified as both environmental and occupational exposures [29,301. Although there is disagreement on the issue of definition, there is agreement that the dose associated with increased mesothelioma risk in these cases is lower than tiiat resulting from usual workplace exposures. Nelghborhood exposures The most ubiquitous environmental asbestos source is from asbestos mining, which produces so-called "neigh borhood" exposures. Studies of mining areas in Australia, .South Africa, and Canada have documented elevated races of mesothefioma among residents who never worked for the mines. Other studies have exam ined neighborhood rates of mesothelioma around facto ries producing asbestos-based goods and found elevated mesothelioma risk (Table 2). Attributing mesotheliomas to environmental exposure is difficult in some of these studies because of their ccologic nature, and it can be difficult to prove an absence of occupational exposure to asbestos in some cases. Rees tt <?/. (311 conducted a large, multieentcr, casecontrol study of mesothelioma in South Africa. Since patients were enrolled as they were diagnosed, exposure information was obtained from live subjects--an excep tion with this rapidly fatal disease. Twenty-two cases (17,9%) had exclusively environmental exposure. The odds ratio for those environmentally exposed in the northwest Cape region (where asbestos is primarily crocidolire) was 32.7 (95% Cl [confidence interval], 8.1-131); for the northeast Transvaal region (crocidolitc plus amosite asbestos), it was 12.7 (95% Cl, 1.9-84.7). A large retrospective cohort study was conducted in Witienoom, Western Australia, the site of a targe crocidolitc mine and mill [32], Mesothelioma was tracked Table 2. Studies oT mesothelioma and neighborhood asbestos exposure Location Year Type of asbestos Source of asbestos Study Type of study population Environmental mesotheliomas to Mesothelioma risk Comments Reference Northwest Italy 19B0-91 Chrysotikt, Industrial crDcxjokte (10%) Retrospective case series Hosptot admissions from focal area NewJewy. 1979-SO USA industrial Retrospective Slate cancer case series registry records Western Australia South Africa { Roving between1 1043 1093 issa-eo Croclcfolite Crocidolito, amosite, ehtysctiie Mining, indualrial Naturally occurring, mining, industrial Retrospective cohort Casrcontrof 4659 resi dents who never worked for mining company Patients in all hospitals tn ix major South African centers Quebec 1970-09 Chrysolite Mining Case-control PopubliCHV based mortality survey 64 Men: 4,2-7,4 Magnani etal. cases per 100,000 person- 135] years Women: 23-7,3 cases per 100,000 person* years Metes: SR-10.1 Berry [36! (95% CO, 5,8-16.4) Females: SIR " 22.4 (95% O, 9.7-44.2) 27 26 cases per 24/27 cases Hansen el *1 100,000 personyears haddomee* tic (farmEsl) 1391 exposure 22 OR-32.7 (95% a, Rees el at [311 6.1-131) for those environ mentally exposed in NW Cape region. OROl 2.7 (1.8-84.7) in NE Transvaal. 7 SMR--7.63 (9S% Some cases Camus era/. 0,3.06-10.03) may have occupa [33J tional expo sure to amphiboles 07019901 374 (taoplasms of Uto lung through a mandatory tumor registry, so ease ascertainment common in several populated areas of the world, and was likely complete. The 4659 people who had lived in exposure co environmental sources of asbestos is thus an Wittenoom for less then 1 month between 1943 and 1993. important public health concern. Human activities that and who never worked for the mining company, were perturb asbestos-containing rock are particularly of enrolled. Twenty-seven eases of mesothelioma were concern due to the high potential for asbestos dust to be found, yielding an age-standardized incidence rate of 26 in released and inhaled. Construction, grading, quarrying, 100,000 person-years for residents aged 15 years or more. or cars travelling on unpaved roads are examples of The rate was similar for males and females. This study did activities that may generate ashesros dust. Also, natural not exclude patients with "familial" exposures, which weathering and erosion may release asbestos fibers into could have accounted for 24 out of 27 eases. One ease the air. occurred in an individual who went to Wittenoom after the mining operations ceased. Exposure to naturally occurring amphibolc asbestos and related fibers is thought to be a cause of malignant A recent study from Quebec designed to test an mesothelioma in several areas of the world (Table 31 Environmental Protection Agency dose-response model Most of these studies have focused on areas of the world for asbestos among women in a chrysntilc mining commu in which asbestos deposits have heen used by the local nity found a high standardized mortality ratio for mesothe population for domestic purposes, such as grinding lioma (7.63; 95% Cl, 3.06-15,03) (33]. However, the study asbestos by hand to make whitewash, insulation, or was designed to specifically address lung cancer, and plaster. This practice has been almost entirely aban mesotheliomas were based on a historical death certificate doned, and the extremely high rates of mesothelioma review, which may be inaccurate. Seventy percent of the seen in these studies resulted from high levels of expo women in the study had lived in the house of an asbestos sure 30 to 40 years ago. The high rates arc not necessar worker, suggesting that familial exposures accounted for ily representative of rates in these locations in the some of the cases. The study has also been criticized future, or in parts of the world in which asbestos is not because high levels of amositc and crocidolite fibers were used for such purposes. found in the lungs of some patients, indicating occupa tional exposure to asbestos in other industry J34]. Naturally occurring trcmolicc asbcscos is abundant in the Metsovo area of Greece. In a retrospective review of Magnani tt at. [35] sun-eyed pleural mesothelioma in hospital eases from 1981 to I9R5, seven eases of malig health authority records of a town in northwest Italy nant mesothelioma were found in a population of where a large asbestos cement factory Was located. approximately 5000, corresponding to 28 cases per Eighty-eight eases of histologically confirmed mesothe 100,000 person-years (37]. In a Follow-up study, the lioma were identified in the area from I960 to 1989, mesothelioma rate had decreased to 14 in 100,000 with no occupational or paraocctipationai exposure to person-years for 1985 to 1994 (38], This drop paralleled asbestos. Mesothelioma mortality rates in men were 4.2 the decrease in domestic use of asbestos, which had to 8.2 per 100,000 person-years; in women rates were 2.3 fallen from 92% of households in 1950 co 18% by 1980, to 5.1 per 100,000 person-years. These rates compared and which disappeared altogether by 1985. However, to national rates based on Italian cancer registry of 1.8 the numbers of eases were small (7 and 6, respectively), and 0.6 per 100,000 for men and women, respectively, so a statistical overlap of these rates is possible. Additionally, the follow-up was not age-standardized, Mesothelioma incidence rates were analyzed in New preventing a direct comparison between them. It is Jersey, in the area of the largest asbestos plant in North likely that the median age of the population shifted America. Berry (361 found standardized incidence ratios upward, which would make the carlict figure relatively among residents in the town with the factory to he (0,1 * undervalued, and the difference in age-standardized for men (95% Cl, 5.8--16.4) and 22.4 for women (95% rates larger than rhe unstandardized figures. Cl, 9.7-44.2) compared with New Jersey rates. Scandardized incidence ratios for the rest of the county Several studies have investigated environmental expo (minus the town) were 1.9 and 2.0 for men and women, sure to tremolice deposits in Turkey. Yazicioglu tt at. respectively. No personal interviews were conducted (39] document a series of mesotheliomas in southeast and some occupational exposures may have been Turkey. In 1977-78, 22 of 23 patients admitted to the missed. regional hospital with pleural mesotheliomas came from Naturally occurring asbestos asbestos districts, which contained only 51% of the population. The mesothelioma rate for these districts There have been few cpidcmiulogic studies looking averaged 9,7 per 100,000 person-years. However, rates specifically at exposure to naturally occurring asbestos. were between 14.6 and 19,1 per 100,000 pcisan-ycars in Naturally occurring asbestos (particularly amphibolc) is the three districts in which asbestos outcrops were most 07019901 Environmental asbestos exposure and mesothelioma Orenstein and Schenker 375 Table 3. Studies of mesothelioma and environmental exposure to mtumltir occurring asbestos Localion Tear Type of asbestos Type of tudy Study population # o( environ. mesothefiomas Mosothefiotaa risk Comments Reference Southeast 1977-78 Turkey Tremo&te Retrospective some case series chrysolite Hospital admfe* stone horn local area Central Turkey Central Turkey Central Turkey 198Q-87 Tremolike, Retrospective Health center some case records chrysolite esriesfcohort 1981-1900 TremoGte Case series Hospital admis- some aionsftom local chrysolite area 1989-1997 Tremdite Prospective esse Patients from one some series dnfc chrysolite Northwest 1981-85 Greece Premolite Northwest 1985-1994 TremoSte Greece Retrospective esse series Cohort Hospital admis sions from tecsJ area Hospftaf admis sions from local area Central 7-1986 Cyprus Chrysotifet some tremofite Retrospective case series Unspecified New 1978-87 Caledonia Tremofite Retrospective case series Unspecified Northeast 1973-91 Corsica Chrysolite, Retrospective iremofite case series Hospital admis sions from Focaf area 23 9.7 case* per Most highly conta Yoscioglu re */. 100,000 pereon- minated 091 yearn silages have trees up to 17 per 100,000 person-years 2 59 cases per Baris e( *1. [40] 100,000 person . yean 77 Cannot tie calcu SeiciAef a/. [41) lated 97 88% of presenting Melimes efai. mesotheRontu 1421 patients had nonoccupaUonaJ exposures. 7 78 cases per Constantopoulos 100,000 person* ttal. [37| year 8 14 per 100.000 Domestic use of Sskefitriou erJt person years asbestos white |3BJ wash dropped from 92% in . 195010 18% by 1980. 4 4 of 12 patients had Mining also McConnochie ef apparent occupa- located in area s'- [46] ttonal orparaoc- eupalioral xpo- wr* 12/9 (see 8-3Z6.2 cases per 12 cases of Goldberg er at. comments) 100,000 pereon- pieur*i cancer, m yeara of which 3 were'proba ble- mesothe lioma 14 10 cases per Rey el a/- {40-1 100.000 person- years frequent. Bum [40] reports two mesothelioma cases in a population of 425 people in central Turkoy over a period of 7 years (59/(00,000 person-years). However, the number of eases and population in this report arc both small and statistically unstable. Additionally, occu pational or other possible exposures to ashestos were not explored, although the argument for overwhelming environmental exposure is convincing. ficlcuk tt at. [41] reported 77 nonoccupational, nonindttstrial mesothelioma eases from 50 ashestos tillages in central Turkey. Metintas rt al. |42] found that 86% of patients diagnosed with mesothelioma in their clinic came from villages with large natural asbestos deposits. I ncidcnce rates cannot be calculated for either of these studies, as the contributing population is not recorded. Rrionite is a nonasbestos fiber morphologically similar to amphibole asbestos. It has been implicated in causing mesothelioma in people environmentally exposed. The Cappadocia region of Turkey is rich in naturally occur ring crionitc and has been found to have exceedingly high rates of mesothelioma in both present and former residents. Mesothelioma is thought to account for 5t% of deaths among villagers living in the area [41,45] and up to 78% of former residents who had emigrated to Sweden [44]. If these figures arc accurate, they suggest that crionitc is more carcinogenic than even crocidolitc asbestos. An interesting study in Cyprus by McConnuchicrt#/. [45] reported on |4 eases of mesothelioma over an unspecified number of years. Asbestos deposits in Cyprus contain mostly chrysolite, but there is some crcmolite contamina tion. The area is rich with natural deposits, bur also has an asbestos mine in die central mountains. These investiga tor; used environmental dust sampling and fitter analysis of human tung tissue to confirm the presence of asbestos in the air. Uniquely, they also used sheep as "mobile air samplers" and further confirmed the presence of both 07019901 376 Neoplawnt of the lung trcmolite and chrysotile in the lung. The researchers suggested that the impact of environmental exposure was high'because the number of occupational exposures among eases was low <5 of 12; 3 more hud familial expo sures, two had neighborhood exposures, and two had no apparent asbestos exposure). However, the article docs not indicate the source of the cases, so the representative ness of the sample is unknown. Acknowledgment W* am grateful (or the technical auifttance of Brigfte Roffe end Kevin Rolfa, end for the capable wA of Ruth ParceH TWe etudy me tuppotted by WOSH Cooperative Agreement #U07/CCU906162-OB, MH pant* ES05707 nd R03 GAIH 515-01* References and recommended reading Papers of particular interest, published wilhtn the annual period ol review, have been highlighted as: Of special interest Of outstanding interest Studies on exposure to naturally occurring asbestos also have been conducted in New Caledonia and Corsica. Goldberg tt ah 147} recorded all cases of pleural cancer between 1978 and 1987 in New Caledonia. There were nine definite mesotheliomas and a further three that were classified as "probable." Of the 12 patients, 3 had worked in thc-nickel industry, which can disturb natural asbestos fibers in the soil. Mesothelioma rates were compared to five reference registries (from France (2), Britain, New York, and Australia). Standardized inci dence ratios ranged from 201 to SI 7. An earlier study by this group (1978-1981) had detected a relationship between pleural cancers and 7/>ncs of residence within New Caledonia; however, the later study did not estab lish an association with particular areas of the country, or with nickel mining sites. Rey ft al. (48] collected mesothelioma cases in Corsica, in an area where both chrysotile and trcmolite can be found, and which is remote from asbestos mines. They found 14 cases in the population, with an incidence rate of 18 per 100,000 person-years. It was ascertained that asbestos-related industries were not the usual occupa tion of the patients. However, otheT asbestos-using or producing industries were not excluded. 1 Rrice B: Analysis of current trend* in United Stale* mesofheSom* incr donee. Am J of Epi 1D97,145(3]:211-2tB. 2 Sngaibeker DJ, Norberto JJ: Mulliinodelity management of malignant pleural meaottwnonm. Cheat 1090,113(1 SuppI):61S-65S. ' 3 Ryan CW, Herndon J, Vogetong Nl: A review of chemotherapy theta for malignant mesothelioma. Chest 1999,113(1 5nppO:S6S-73S. d Huncharek M, Ketaey K. Muacat 1. Chrtalianl D: Parental cancer and genetic predisposition tn maSgnant pleural mesothelioma: a case-control etudy. Carar letters 1996.102(1-2):205-208. 5 Hubbard R; The aetiology Of metottieliomt'. are hak factors other than asbestos exposure important? Thorn 1997;62:196-497. 9 Paterson JT, Greenberg SO, Bufflef PA: Non-asbestos-idaled malignant mesotheSoma: a review. Cancer 1984.54:951-960. 7 Booth Si, Weaver HJM: Melignanl pleural mesothelioma free years alter domeatic erpoaure to blue eehastos. Lancet 1966,1:435. - S Branch! C, GfemSi l. Grand G, et el: Latency periods in aabestosselated mKOihelwna of the pleura. Eur J Cancer Prevent 1997,6(21:162-166 9 Rosier JA, Woitowitz HI. Lange HI, et al.r Modality rates in a tamale cohort following asbestos exposure in Germany. 1 Occup Med 1694, 36(81:669-693. 10 Wagner JC: Asbestos-related cancer and tre amphibota hypothesis: the first documentation ol the association. Am J Pub Hlth 1997, e7(4):667~6ea. 11 banger AM, Nolen RP: Asbostoe-rstated cancer and the amphawle hypoth esis. The amphfcote hypothesis: neither gone nor forgotten. Am J ol Pta> Hlth 1967. B7(4)r888-689. 12 American Thoracic Society: Health effects of hematite. Am Rev of Respe Die 1992, U2[6 Pt 1):|453-I458. 13 McDonald JC, McDonald AD, Hughes JM: Chrysotile. trcmolite and tttrageiriclly. Ann Occup Hyg 1999,43(7):439-442. 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However, many questions remain unan swered about the contribution of environmental asbestos exposure to the development of mesothelioma. These include the extent and nature of asbestos expo sure in nonoccupational environments, the proportion of mesothelioma cases with purely environmental expo sure, and the relative risk of chrysotile and amphibolc asbestos. These issues have direct public health rele vance for many areas in the world where development is occurring in areas with naturally occurring asbestos. IT Sturm W, Menlo B, Kraus* A Thriene B: Asfaestos-nlatsd diseases snd asbestos types toed in the former GDR. Ekper Trariool Peth 1995, 47(2- 31:173-178. . 18 Rodeleperger K, WOHowitz HJ, Brocket B, et efc Dose-response relationehip between esnptribole fiber lung burden and mesothelioma. Cancer Detect Prevent 1999,23{3):iaa-103. 19 Wagner JC, Staggs CA, Marehsnd P. Diffuse pleural mesothefioma and asbestos exposure in the North Western Cape province. 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