Document Zp7x2Vp4byxE3g0eYgpNEad

/99? -i ' ' AMERICAN JOURNAL OF IN0USTR1AI MEDICINE 3S:2I 3-222 (1999) Case-Control Study of Mesothelioma in South Africa David Reesr mbbch. doh, msc (Med), PhD, MFOMi '* Jonny E. Myers, mbcHb, esc* mdvz Kim Goodman, knrm, mba,1 Elize Fotirie, M&ciiB, Mmed (Rarfrh* Charlttie Blignaul, mbceb, doh, MMtd/ Ronald Chapman, BSc, mbbch. mmec^ch),1 and Max O. Bachmann, Mache,doh, msc, ffch,mfphm* Background South Africa has, uniquely, mined, transported, and used crocidolitc, amositc, and chrysotile. A muhicenter case-control study was done in South Africa to examine the details ofasbestos exposure in cajej and controls, and to calculate relative risks for level of certainty of asbestos exposure, nature of exposure (e g-, environmental, occupational) and fiber type, . Methods Cases and controls (one cancer and one medical per case) were collected bv six Study centersfrom referral hospitals, and exposure information him collected by inlerviewing cases and controls in life,, R^cults One hundred and tv.'cnty-ikrcc cases were accepted into the study. None had purely chrysotile exposure. Twenty-three cases had mined Cape crocidolitc; three hod mined amositc; and three Transvaal crocidolitc plus amositc. A minimum of 22 of the Cases had exclusively environmental exposure, 20 were from the ATV Cape crocidolitc mining area. The relative risks associated with environmental exposure in the AAir Cope (crocidolitc) were larger than for environmental exposure in the NE Transvaal (amositc and crocidolitc): 21.9 i\s. 7. / and 50.9 rj. 12.0for the cancer control and medical control datasets, respectively. Conclusions The results confirm the importance of cmitnnmcnltil exposure in the Cope crocidolitc mining urea, the relative paucity ofcases linked to amositc, the rarity ofchtysotile cases and arc consistent with a fiber gradient in mesotheliomagenic potential for South African asbestos with crocidolitc > amositc > chrysotile. Am. J. lnd. Med. 35:213-222, 1999. O fW HVcy-Uss, Inc. KEY WORDS: mesothelioma; South Africa; ease-control; asbestos; chrysotile; amositc; crocidolitc 'National Centre tot Occupational NeaWi and Community Hearth Department, University of Witwalervand. South Africa department of Community Hearth, University of Cape Town, South Africa 3Department of Health, Welfare and Environmental Affair?. Northern Cape Province, South Africa ^Department of Community Heart!i. Unrvorsjty of Pretoria. South Africa sCommunity Hearth Department, tfriivcrsrtyol it* Free Slate, South Alrica Contact grant sponsors: the South African Medic* Research CouncH. (lie Anglo Aroertan and tfe Beers Cn,iirman`s fund, and hvc National Cancer Association of South Aihca `Correspondence to: Davd Rees, totonal Centre for Occupational Hcaflh tUCOH). PO Bo* *?63. Johanncsiiwg 7000. Soulh Africa E-man u^vidiS'ncofi pwv.gov.ja Acrpplcd?l OcloU-r 9y3 INTRODUCTION South Africa has, uniquely, mined, transported and used crocidolitc, Jimositc, and duysotilc. the three main commcrcuf varieties of asbestos. It is, thus, no surprise that mcsothcliuruj rates arc relatively high [Zu-j ei a!.. 1989]. Somewhat surprising, though. is the paucity of local cpidcrititilugic studies of this disease -- many questions about iLiCM>tlieliom;i in Siiulh Africa remain unanswered, among them ihe rckirive cotitribuiitui cadi variety of asbestos iiKihcs to the case load: the extent and nature of asbestos exposure m a representative group of eases (for instance, die pmpniiion of case's wiih juirclv vimmnnwutal exj'Kisiire); 1999 Wiley-Uss. Inc. 2 I 4 Rees elal. and the relative risks associated witli the different fiber types and exposure settings. These questions are of more than local interest The amphibolc hypothesis, which has it that amphiboles are die only asbestos which cause mesothelioma, is topical and controversial [Stayncret ah. 1996; Smith and Wright, 1996|. and South African asbestos has been exported to many countries. The data reported here are from a South African multiccnier case-control study. The major objectives of the study were to examine asbestos exposure in detail in South African cases and to calculate relative risks for level of certainty of asbestos exposure (i.e., definite, probable, possible, and unlikely), for category of exposure (e.g., occupational and environmental) and for fiber type. Nonas bestos agents and mesothelioma and (he possible protective effect of consumption of vegetables on the development of mesothelioma were also studied; these results are reported elsewhere. MATERIALS AND METHODS This muhiccntcr case-control study of mesothelioma used a secondary base of referral hospitals for cases and controls and collected exposure information prospectively; cases and controls were interviewed in-life by trained interviewers using a standard questionnaire. Cases Our intention was to include all cases treated or diagnosed in the study centers over lire study period. To achieve this, all pathologists, oncologists, cardiolhoracic surgeons, and respiratory physicians registered in the study centers were invited by mail and telephone to refer new cases to the research teams. In addition, to encourage participation, key practitioners most likely to encounter cases (for instance, heads of units in large hospitals or practitioners with a known interest in the condition) were visited by research teams. All of these medical practitioners were reminded regularly of the study and were sent brightly colored reminder cards at intervals fordisplay in their rooms. To reduce diagnosticmisclassification (increase the true positive rale), cases were entered into the study only if a specialist pathologist diagnosed Tnesotlielioma, the histo logic diagnosis was supported On review by a member of the South African Asbestos Tumour Reference Panel (a panel of experienced specialist pathologists established to standard ize the histologic diagnosis of mesothelioma), and immunohistochemica! staining supported the diagnosis with a mini mum requirement of negative staining for carcinocmbrionic antigen (CEA). Controls Study Centers and Research Teams The study was conducted in die six major industrial comers of South Africa, and each center included all hospitals within 50 km of the city center. Greater lilocmfontcin, Cape Tow n, Durban, Johannesburg, Kimberley. Port Elizabeth. and Pretoria W'crc selected as study centers because they art die major industrial cities and arc geographi cally located so dial their tertiary hospitals serve much of South Africa, including lire asbestos mining regions (without being in an asbestos mining district itself)- Durbin was later abandoned as a study center as it did not operate success fully. A research team comprising a coordinator and two interviewers, between diem fluent in English and the predomi nant vernaculars, was established in each study center. Each team was (rained using a detailed interactive instruction manual as pre-reading followed by a day-long training session. Interviewers were blind to ease-control status of subjects and did not know dial die primary research ques tions concerned asbestos and mesothelioma. Research teams operated for about 16 months, from late 1988 through early 1990. (The relatively short duration for case collection was to prevent declining motivation of researchers likely to occur over an extended study period.) Motivation was maintained through regular contact, a newsletter, and prac tice interviews w-| len long periods Itctween cases occurred. Two controls, one with a medical condition and (lie other with cancer, were selected for each case. Cases and controls were matched on the hospital in which the case was interviewed, skin color, gender, and approximate age (within 5 years). General exclusion criteria for both medical and cancer controls were that they should not have asbestos- related disease or an undiagnosed condition (i.e.. diagnostic investigation incomplete). Controls with lung, pleural, or peritoneal malignancy were excluded, as were patients disoriented for time, .place, or person and individuals with conditions of the central nervous system (to avoid selection of controls with disease-related memory deficits). To in crease the likelihood that cases and controls were from the same population base with the same referral dynamics and pressures into the source hospital, controls were limited to patients with a serious condition likely to warrant similar medical referral pressures as patients with tlic signs and symptoms of mesothelioma. Referral hospitals often serve the primary medical care and secondary level needs of die local community as well as providing tertiary level services. To avoid misrepresentation tlirouglt selection of these pa tients witli relatively minor conditions; (unlike tnesotlielioma cases), skin cancel patients were e\cludcd as were all medical patients with fewei Ilian live m-palicm days (for the cuiTcnl admission) Mcsolhctioma in South Africa 21 S Exposure Information Exposure information was obtained directly from cases and controls by (I) the administration of a structured questionnaire after obtaining written informed consent; and (2) the examination of sputum samples for coated libers. The questionnaire A detailed questionnaire on residential and occupational history and domestic exposures was administered in die preferred language of the subject in a standard manner by die interviewers. To reduce interviewer bias, questions were largely etosed-ended or tightly structured, thus allowing little interpretation by the interviewer even if case/control Status was inadvertently known. Some open-ended questions were asked toward the end of the interview to promote completeness ofinformation. The questionnaire included a residential history (town and magisterial district), lime spent near dockyards, mines, mills, asbestos using factories, stores of asbestos, parents' occupation, domestic and leisure time exposure to dust, a complete occupational history with detailed questioning on asbestos exposure, and questions on diet and tobacco smoking. Two components of the question naire were developed as "memory joggers" to aid recall of particularly important potential sources of asbestos expo sure. One seciion enumerated districts in which asbestos had been mined and the other listed important industries, occupa tions, and activities with a known risk of asbestos exposure. The industry and occupation lists were compiled by collat ing information from three sources: literature, consultation with experienced occupational health practitioners, and the patient database of die Occupational Medicine Clinic of the National Centre for Occupational Health (NCOH). General references [Health and Safely Commission, 1979a,b; Michaels and Chissick. 1979; E'amieggianr, 1983; Nicholson cl al.. I982| were consulted to compile an initial list. To this was added the important exposure settings reported by patients who had attended the clinic -- patients u-crc cross-filed by exposure category and these were used. The list was then refined by two experienced occupational medicine practirioncrs and two experienced occupational hygienists who together produced the final 31 primary' memory joggers or occupational risk settings (Appendix). Nandiffcrcntial recall bias favoring greater recall by eases is theoretically possible if cases have been questioned repeatedly prior (o the study interview, or if an advantage (c.g., compensation} is conferred through a positive history. To reduce this bias, rases were interviewed as soon as the diagnosis was suspected (829!- of cases had llieir first exposure history taken by an interviewer for this sludyl and subjects were not told that the study related to asbestos specifically, but rather explored a variety of diseases and exposures, ilui-. placing cases and controls in the same position regarding possible work-relatedness and compensa tion. Coated fibers itt sputum The validity of exposure data derived from question naires is affected by failure to recall or recognize past exposure, in an attempt to identify some of the "failures" in this study, spontaneous sputum samples (i.e,, sputum samples not induced by inhalation of aerosol) were collected from subjects for evaluation of coated fibers. (The term coated fibers is used synonymously with ferruginous bodies.) An attempt was made to collect two sputum samples from each study subject, the first after completion of the questionnaire and, in an attempt to collect a 24-hr sample, a container was left with the subject for post-collection in a prepaid enve lope. Sputum examination was done at the NCOH by experienced technicians blind to case-control status using a standard technique (Smith and Naylor, 1972], Asbestos Exposure Categories Subjects were grouped by probability of exposure to asbestos (exposure class), lire likely fiber type, and the nature of Ills exposure (e.g., occupational or environmen tal}. : Exposure dosses Tabic 1 shows the criteria for allocation of subjects to one of definite, probable, possthlc, or unlikely asbestos exposure class. The magisterial districts of South Africa were divided into five groups; N\V Cape (Cape crocidolitc mining); NE Transvaal (amosite and/or Transvaal crocidohte mining); E Transvaal (chrysolite mining); "Other" districts (minor asbestos deposits -- anthophillite, chrysotilc, or uemolitc mined in a small loeality for a short period in some districts); and nonasbestos districts (no asbestos deposits). The period spent in any of the asbestos districts was recorded for each subject using the questionnaire data. (Note; the boundaries and names of South Africa's provinces have changed but the old names have been retained in this article for concordance with previous literature. NW Cape is now Northern Cape Province and North West Province, NE Transvaal is the Northern Province, and ETransvaal is Mpumalanga.) Living "near" an asbestos mine or mill was not restricted to a specified distance, since it is well known that extensive areas around mines and mills were contaminated, particularly in the NW Ca|te (Marcliand. 1991] and Nl: Transvaal [Pclix ct al.. 1*>9-1 j. "High risk" occupations sir activities are those listed in the Appendix in which asliestos exposure was thought to tv probable even if the subject slid not actually ternll exposure. I A. (\ !;. 1,. M. P. R.S. 11. and 21G Rees et al. TABLE L Cffleria lor AHoeating Cases and Conlrols to Asbestos Exposure Classes Definite 1. Direct orindited opojpational eipoore itportnl. 2. Gott&d with asbestos while spending time b an asbestos mWng'dtstrict (contact incfcjdcd playing on tailings dumps; living near a mine or milt, parent wotting in a mine or mill; asbestos liber contaminating wort; or domestic environment). 3. Domestic exposure reported, notable 1. Worked in "High risk" occupational or activity without recall o( occupa tional exposure. 2. Spent 12 months or longer in an asbestos mining district o(Wtf Cape, HE Transvaal, or E Transvaal without reported contact with asbestos. 3. Coresident worked with asbestos products in the residence. Possible 1. Worked in a "Disk" occupation without recall ol occupational exposure. 2. Spent less than 12 months in NW Cape, KE Transvaal, or t Transvaal district wfttioul recall ol contact. 3. Domestic use ol asbestos cement products or heating panels, a. Lived or worked in an asbestos cement structure. S Lived or worked within t km ot a docicyarj ,,beStos product manutac- turing laclryy. G Uncertain direct or indirect occupational exposure reported. Unhkely . Mo recall bt exposure. No "Kick" or "High risk" occupation or activities Lived in "OSicr" disbict wisiout reported contact ' V were labeled "High risk" while ihc rest of I (excluding sugar-cane) and 1 were labeled ''Risk" occupations oi activities. Ollier districts mined asbestos in limited quantities in a small section of the district, often for only a relatively short period. Consequently, asbestos exposure was considered unlikely merely as a result of residence in other districts -- reported contact with asbestos, however, led to a classification of "Definitely exposed." . Fiber type Whether asbestos exposure had occurred exclusively to a single fiber type could not be determined confidently in many subjects. For example, asbestos cement product users (clirysotilc plus amphibolc or only clirysolilc in more recent times), and those with possible exposure in a risk occupation or residence in a number of NE Transvaal mining districts (amosilc and/or Transvaal crocidolitc). For this reason, fiber-specific odds ratio calculations were limited to three situations: t District-specific risks -- subjects with aslicstos exposure exclusively in the NW Cajic (Cape crocidohte). NE Transvaal (amosite and/or Transvaal crocidolitc), or E Transvaal (chrysolite) were used for these analyses. 2. Those in whom crocidolitc exposure had occurred even if this was not necessarily limited to crocidolitc. Subjects in this category were those who had spent time to the NW Cape (residence, mining crocidolitc. transporting crocidotiie. etc.), who reported exposure in the manufacture of battery casings or large diameter water pipes and those who reported crocidolitc exposure (for example, blue asbestos mining or milling). 3. Workers with exposure exclusively in asbestos mining or mining-related work. Nature Nature of exposure was. categorized as occupational, environmental, domestic, or incidental. Direct occupational was use at work by the subject while "Indirect" was exposure due to the use of asbestos by coworkers; "High risk" and "Risk" activities arc shown in the Appendix, "Environmental-mining" was exposure due to contamina tion nf the general environment by asbestos mining, millin". and related activities, while "Environmemal-otJicr'' expo sure arose from living within a kilometer of an asbestos using factor)', store or asbestos, or dockyard. Domestic exposure occurred at home due either la contaminated workclotltcs (Domestic-clothes) or work with asbestos prod ucts (Domestic-use), which included hobbies and the servic ing of motor vehicles' brakes. Incidental exposure was use of aslrestos cement garden furniture, spending lime in asbestos cement structures, and use of asbestos hcatine panels. Data Management and Analysis All data were coded blind to the casc-comrol status of the subject by the principal researcher, and subsequent allocation to exposure classes, fiber types, and nature of exposure was done without knowledge of diagnosis or sputum results. Questionnaires were double-punched and the datasets were compared and corrected by referring to the original questionnaire. Univariate and bivariate statistical analysis was done with the assistance of the Epiinfo Vcrsion5 software pro gram jDean cl al., 1990). Conditional logistic regression was used to calculate odds ratios (OR) and 95`rt- confidence intervals (Cl/ using the EGRET Software Package (Egret. 19911. I'he cases and cancer controls and cases and medical controls were treated as two separate datasets, unless otherwise staled, ami matching was retained in analysis. In sonic analyses, medical and cancer controls were pooled with a view to examining the effect of greater power on the efloct estimates and their confidence intervals, on the assumption that the two sets of cnnitols did not represent Mesothelioma in South Africa 217 different populations. In these pooled analyses, matching TABLE II. Characteristics of Mesothelioma in Case-Control Study in was also retained to produce triplets "of one case and two South Africa 1988-1990 - controls and conditional logistic regression was used to calculate ORs. Odds ratios and 95% Cl were calculated for Site* S Age class and nature of asbestos exposure and occupationspecific ratios were calculated for Cape ciocidolife miners Pleura Peritoneum Male Female Mean (SO) and for workers who had had contact with asbestos insula Johanoesburg n - 4S at 3 43 ' 5 55.8 (13) tion material and for workers using asbestos cement. Pretoria n = II 20 i 15 6 58.2(111 RESULTS Kmbeifcyn = 72 20 2 tfi 6 52.6(17) Bloemfontein n = 19 19 1 16 3 523(18) Cape Town n = 10 10 0 9 1 58.9(15) One hundred and twenty-three cases were accepted into PortOtotethn = 3 the study, tumor site, sex. and mean age are shown by study TOTAL (K) 3 115(94] ' 0 7(S) 3 0 S7J(7) 102 (S3) 21 (17) 55.4 (12) center in Table II. Onc.hundred and nineteen cancer controls and 103 medical controls were available for analysis. Since -Endudes pericanlwnu Jotennesbug = t case. there were 123 cases, the datasets were four cancer and 20 medical controls short. This arose in the cancer control dataset because of inappropriate controls being selected TABLE Itl. Mesothelioma Cases and Controls by Exposure Class.'' South Africa 1985-1990 * (c.g., not matched by age, hospital, or skin color, or disease not a cancer) and in 19 medical controls because medical Cases Cancer cerctrois Medical centreIs controls were not interviewed in the Bloemfontein region Class and litis could not be rectified before the study team was n{S| l*l n(S) disrupted. The remaining medical control had a pleural effusion and was therefore excluded as mesothelioma was possible. Tabic 11! shows the subjects by exposure class. There was no significant difference in exposure class between the two sets of_comrols. Definite Probable Possible Unlikely Total 94(751 It (11) 121101 5(4) 123 24(20) 16[13| 39 (33] 40 OT 119 20(19) 15(15) ' 33(32) 35 (34) 103 The nature of asbestos exposure (as explained above) is -Set lido I shown for cases and Controls in Table |V. Only three cases were categorized '"None'" -- ihcse three plus the two cases categorized "Ollier" district only make tip the "Unlikely" class of Table Hi. The two control groups were very similar in iticir distribution of nature of exposure. Twenty-two cases (17.9%) had exclusively environmental exposure in one ofthe three main asbestos mining regions; 20 in the NW Cape, one in the NE Transvaal, and one in both the E Transvaal (309 months) and the NE Transvaal (3 months). Two cases had "Domestic-use" as the major source of exposure: one built his own house and cut asbestos ceilings and the other was exposed while her husband insulated their house. An inspection of the house revealed asbestos lagging on water pipes between the roof and ceiling. Tlic lagging material was examined by X-ray diffractomctry and found to be 0.5-1% chrysolite and 0.5-2% cither amosite or crocidolilc (per sonal communication, RSI du Toil. NCOH, 19S9). This woman had another possible source of exposure as she had named by controls h is notable that no subject had worked at a chrysolite mine. A proportion of the cases and the controls had had no asbestos exposure other than that which may have occurred due to living in or visiting an asbestos mining district or from occupational or other contact with the district-specific asbestos while spending time in the particular district. In these individuals, asbestos fiber type could be confidently identified, as the exposure had been exclusively in tlic mining district to the asbcsios mined in the district. These individuals arc presented in Table VI by case-control status. The subjects presented in Table VI include all those with occupational mining-related exposure shown in Table V (n = 35) plus 57 other subjects whose only asbestos exposure was district-specific while working, residing, or spending time in an identified mining district. No case worked as a pay clerk and visited consiiitLiion mics hit about reported E Transvaal exclusive exposure. 30 min per week for many years. Tabic VU presents ORs and 95% CIs for cases matched Tabic V presents cases and controls grouped into four with a cancer and a medical control (ix.. 1:2 matching) and major occupational exposure categories. Twcntv-eight sub for cancer and medical controls separately (1:1 matching). jects had worker! on Cape crocidolite mines. Two or these In the 1:2 matching, only 103 triplets were available for mines are unknown rllceslmcl. and Ruddies! -- Ixnh were analysis since complete triplets could not be formed unless 21E Rees ct at. TABLE IV. Mature ol Asbestos Exposure in Mesothelioma Cases and Controls, South AJrica, 1988-1990 TA6LE VI. Subjects With Asbestos Exposure Exclusively in South African Asbestos Mining Districts Kahn Case Women case* Cancer confab Medical control^ N *{%i (*i |X)- Occupational Direct Indirect *>11311 risk1* -RiskUncertain EnvirorMTKfltal Mining Other +Uncertain occupational +"flisk" "Other'' district only Domestic domes Use Incidental None total 63(51) 9(7) 0 8(7) 2CI 1(5) U5) 0 0 c 2? (IB) 0 4(3) 8(G) 2(2) 15(71) 0 1(5) 0 1(51 0 2(2| 0 3(2| 123 1(51 M5I 21 13(15] 3(75) 1(1) 23(19) 1(1) H 111) 3 PI 1(1] 19 (18) 3(3) 15(13) 3(2.5) a 12(13) 2(2) 12(12) 2 PI 2 Pi 8(8] 10) 0 1(1) 2(2] 33(32) 1T9 0 0 212) 33 (32) 1D3 TABLE V. Major Categories of Occupational Asbestos Exposure ir. South Alrican Mesothelioma Cases Asbestos ccrticnl Mining anrfrcialed wort/------------------------ Budding Inflation CC TC A Tt t A Ct products Pipes wort, Cases In = 123) 23 1 3 3 0 Cancer control <rt = 119) 200 0 0 Medical ayfimb 3 00 o o 10 q 5 2 0 0 22 4 C ion ' 1 f. . CC - Cap crotitoMe. 1C *= IrartswaF c/oodoile. A. = Amosrir, Cr - Oirrso4rt< 'TC mine - Torrsvaif Blue Astasias: A nine = Pcrge; TC < A mines - walshtonc {ttahtehCoajlftd Makapeng (Mafdrt lucwwflAafett|. CC ttwg *= Bretby, Cape Blue Astasias, CBM. KC8. Koegas. Kuruman. rental. Rirms. Viliftcbank. BeCStoti; Rodrtcs Cases . Cancer controls Medical twhofc; Region "00 pr n fK* N WCape HE Transvaal E Transvaal "Other'' 44 (36] 2(61 0 2(2) 11(3) 4(3) 6(3) 3 PI 2(2) AW 2(2) 2(2) UunbetofGCa = l2AcaNttrrobot B119,medal controls 103. Terart of a* case* or contnfe. TABLE VTL OR lor Mesothelioma According to Class and Mature of Asbestos Exposure1 Asbestos exposure Cancer and medicat' Cancer conIrate Medical controls OR 95% C| OR 9554 Cl OH 9554 Cl Possible 4.4 0.96-20.5 17 0.4-B.2 H?.9 0.S-108.7 Probable Definite 5.5 1.4-22.5 587 14.0-246 7.5 40.E 1.7-37 9.2-109 10.S 1.2-89 104.5 10.6-1026 Nature* Occupational Environmental 80.G 15.7-4 14 19.G 37-105 45.9 12.2 8.0-262 2.2-67.0 36.9 15.1 9.7-182.8 3 3-793 'Rsk"gecupa- lion 15.9 29-84.3 3.3 0.5-20.2 2.3 0.4-13.9 Occupational Mining CC 65.5 14 5-585 1GG.5 11-2339 MS.4 <1.2-1655 Jusulabon 7G.4 U.4-40S 1G3.3 11.2-2374 67.3 87-91B Asbestos cement 27.7 4.9-154 13.8 2.3-83 43.6 3.9-486 Environmental* NWCape IIE Transvaal 32.7 12.7 8.1-131 1.9-84.7 21.9 7.1 4.7-102.4 02-171 50.9 12.D 7.2-350 1.2-117 Cioddotite <2 months 29.7 2.8-151 S.6 0.6-37.9 31.9 2.1-492 any 72.7 Mi-355 57.9 10.9-309 68.1 8.0-578 CO - Cwcrowtotfa. Hjasclwd of eiposure = rl*ely exposure dm. XktupotaruT - 0*kI or indirect occupation* eiposu'e reported by stftftct, C/wonmenu - lime sperfl in i rmning district ffve only source ot tqttSwrt (Usk occupation = ivortiedrt a kRrsX"oo3ipatjOO>saci3tt!4*ith dtasutt bat ao reran *1 2 Mjirtwg vrith t*sc *nd a medcaf plus s cancer conlrat. both a medical control (n = 103) and a cancer control (n = 119) were available. The ORs increased a& class of asbestos exfK>surc increased from possible to definite exj>osure. but the pos sible and probable dosses were similar for the cancer and medical control combined dataset ond for the medical Controls alone. ORs foi only three categories of nature of asbestos exposure arc presented in tlic table, namely. Occu- paiiuttal (shown in Table IV as direct or indirccl Occupa tional), liiivironmcnlal (Table IV (environmental mining) and "Risk" occupation. ORs could not be calculated for (he other categories due to tlic small number of cases in these categories (Table IV). Working in a "Risk" occupation without recall of exposure was significantly associated with mesothelioma only in (lie dataset with ln>th medical and Mesothelioma in South Africa 219 cancer controls -- the other analyses produced a lower 95% Cl of less than l. It is notable that working with asbestos cement (relative to no asbestos exposure) was strongly associated with mesothelioma in all three datasets. There were no exclusively E Transvaal cases; ORs could not, therefore, be calculated. Even short contact with croeidolite (<2 months) was associated with a fairly substantial relative ri sk of mesothelioma in the cancer -1- medical control dataset (OR = 20.7) and in the medical control dataset (OR = 31-9). marked bias in exposure classification. The similar ORs for the possible and probable exposure classes, particularly in the medical controls (seen in Table VII) suggest a lack of distinction between possibly and probably exposed. One explanation for the poor distinction may be the 12-monlh boundary used to separate possible and probable exposure consequent on spending lime in an asbestos mining district (Table I). DISCUSSION Environmental Cases This study confirms the importance of environmental exposure in the croeidolite mining area of the NW Cape (now Northern Cape Province), the relative paucity of diagnosed cases linked to amosile, and the rarity of chryso lite cases. Results arc consistent with the view that there is a fiber gradient in mesotheliomagenic potential for South African asbestos with croeidolite > aniositc > chrysolite. In the main, limitations of this study relate to represen tativeness of cases and possible misclassifscalion of expo sure. The number of cases who should have entered the study is not known, but indirect evidence suggests that ascertainment of diagnosed cases was reasonable; tbc only incidence study in South Africa [Zwi et al,, 1989] registered 109 cases per year on average for 19SO-I984. (This was for the whole of South Africa and histologic confirmation of the diagnosis was not necessary.) More importantly, there is evidence that die 123 cases who entered our study niisreprcsemed South African cases in sonic respects. Fifty-five percent of the cases were white, ycr this group makes up only about 20% of South Africa's population Poorer access to health care by black Sotuh Africans is a likely explanation (Zwi cl ah, 1989), but the effect of tills underrepresentation of black subjects is unknown. No study team was success fully established in Durban (KwaZulu-Natal Province), but Durban has a major harbor which exported asbestos (mainly chrysolite). The proportion of cases collected in Krmbcrcly (22/123) was not as large as expected, given the historic importance of this region. A proportion of suspect cases was diagnosed clinically and not confirmed by pleural biopsy; they were thus not included in the study. In summary, although ii cannot be quantified, it is possible that this series of cases underrepresents cases with environmental exposure ro Cape croeidolite and those w ilh harbor-related exposure. A number of strategics were adopted in this study to limit misclassificalicin of exposure. A variety of indicators suggest (hat this was successful; the high rate of reponed adwstos exposure m cases points to good detection of exposed subjects; no subject classified in the uni ike I y esposure class had coated fillers in the spulum. and 19 of (lie 21) subjects witli coaled fitrers were classed definite ot probable -- the remaining subject, classed possible, had '-inked in a "Risk" occupation for 38 years; die very simitar e S|>OMirc politics in ihc l" ii sets of controls iiulitates against The large proportion of cases with purely environmen tal exposure is unique to South Africa. Australia is the only other country to have mined croeidolite in significant amounts and it has maintained a mesothelioma surveillance program since 1979. Ferguson et al. [1987] presented exposure data on 726 cases collected from I/1/I980 to 12/31/1985. Environmental exposure had occurred in 43 of these cases (6%) and in only six of these (less than 1%) was environmental exposure due to residence in an asbestos mining region (Wittcnoom, the croeidolite district). This is about one case per year -- a sharp contrast to Ihc findings of this study. Other mining countries do not report environmen tal mesothelioma to any extent; for example, McDonald and McDonald (1980] examined ihc exposure histories of 480 cases of mesothelioma in die USA and Canada. Neighbor hood exposure (i.e,, exposure recorded as exclusively resi dence within 20 miles of a ehrysolile mine) was found in one USA case and in none of the Canadian cases. Fiber-Specific Data: Relative Importance of the NW Cape and Paucity of Chrysolile Cases In all study centers the majority of cases who bad spent lime in an asbestos mining district had done so in Che NW Cape. The majority of cases who had mined asbestos had mined NW Cape croeidolite (Table V) and die majority of cases with asbestos exposure exclusively in an asbestos mining district had this exposure in the NW Cape (Tabic VI). Of Utc 22 cases with only environmental exposure, 20 (91%) were exposed in the NW Cape. Besides a greater mcsothciiomagenic potential of NW Cape croeidolite, explanations for this preponderance of cases with NW Cape mining district experience arc: these districts mined much more asbestos (ban Ihc other districts: the nature of the mining operations led to contamination of a much larger area; and (hey generated much more dust, thus exposing more people to more dust. Tiic first suggestion is the easiest to examine. As shown in Table VIII, it was only in ahoul i960 that crocidoliie production exceeded that of amosile, and amosile and chrysolite production was substantial throughout the 1960s 220 Rees et al. TABl VIIL Asbestos Production and Estimated Number ol Miners by fiber Type South Africa 1940-1975 Jeiestos praduetjon* 1940-19SS in kik*ws, 1960-1375 in ndiic liSAmt Cape oeektoSte Aawsiti ChtysstJe 1340 7 IB 1345 R 17 1950 1955 15 35 42 50 I960 71 fi? 27 1970 137 97 3 197S US Sfi 100 timber of asbestos miners f% of JU asbestos miners) 1960 1970 1975 Given the contamination of mining regions in the NE Transvaal and that the NW Cape is a sparsely populated region, it is untenable that the preponderance of NW Cape cases can be explained merely by * preponderance of individuals exposed in die NW Cape. ORs could not be calculated for cases exposed to only dnysotile, since nosuch cases were identified, but Table VII shows larger relative risks for environmental exposure in the NW Cape than in the NH Transvaal. The large relative risks associated with Cape crocidolile mining, insulation work, and wort with asbestos cement products is notable- The asbestos fiber type to which subjects were exposed in the latter two work situations cannot be determined with confi dence from the questionnaire information. Cape Croddotite* Arrastte* CtirysoUle1 2.600(17) I2.000-U.003 7.000 '.TOO Source 01 data IM0-195S Webster. 197J. 19CO-197S Rut 1983. Source ol data, fed* at.. 1990. Souiceofd3U.rlu1ofl. 1993. 1,500 and early to mid 1970s. (Given the long laicni period for mesothelioma, more recent data arc not of real interest.) Twenty-seven, 53, and 100 metric kilotons of cliryscnilc were produced in I960, 1970. and 1975, respectively (Han, I9SS], It is true that NW Cape crocidolile mining rook place over a wide geographic area, but extensive contamination of the NFI Transvaal has Iwcn well documented (Felix cl a!.. I99-1J: pollution by asbestos of surrounding villages and the environs was extensive (for example, ai Icasi nine mills operated in die Mafcfc district, each with a large asbestos waste dump), and disease due to environmental exposure was common in mining areas (for example. 389 of 611 randomly selected adults from Mafcfc had a history of environmental asbestos exposure and 34% of these 389 individuals had pleural disease). E Transvaal (now Mpum alanga) chrysolite communities have not been studied, the extent of environmental pollution experienced by these communities and of asbestos-related disease in (hem is not known. Dust levels in and around NE Transvaal mines and mills were very high (dust counts taken in the Pcngc mill remained well above 12 fibcrs/ml until after die second half of die 1970s) (Felix cl al., 1994). Published studies of fiber levels in E Transvaal chrysotilc mines arc sparse; the only readily available data are from Slade's thesis (19311. 'flic lltcsis provides convincing evidence of uncontrolled dust levels (the concentration of dust in the atmosphere was such that objects were rendered indistinguishable at a distance of a few yards) and of high disease rates (of 1 IK) chrysotilc mill workers examined. 7-1 bad an abnormal finding consistent wirli ashestosis (Felix ct al . 1994)1 Paucity of Chrysotrlej^ases ' No case with a history of cltrysotilc mining entered llic study, nor did a case with exclusively environmental expo sure to chrysotilc. Although no case could be said lo have h3d good evidence of exclusively chrysolife occupational exposure, two reported contact with this material, and little if any work with ampltibnlcs. One of these spent 369 months in chrysotilc mining districts and 3 months al an asbestos mine in the NE Transvaal -- he had amphfboles isolated from pleural biopsy tissue. The other case is intriguing: despite repeated questioning for clinical and compensation purposes, the only historical source of asbestos exposure was to chrysotilc. which began only 4 years prior to diagnosis.This is a very short latent period and docs not lend itself to causal interpretation. An ampltibolc. probably incnioliic, was seen in pleural material examined by scan ning electron microscopy; this may have been a contaminant of the chrysotilc to which she was exposed. Tltis absence of South African chrysotilc cases is nol an isolated finding. Mesothelioma cases from South African chrysotilc mines have not been recorded (Wagner. 1986). One explanation for the absence of exclusively chryso lite cases is that production and use of die material in South Africa w-as so limited lliat the small number of exposed individuals has resulted in a paucity of cases. This seems unlikely, as is shown in Table VIII, Hart (I988J estimates chrysolite production al about 30% of total asbestos produc tion by the end of the 1970s. In the early 1960s, production was closer to 20% (Hart. 1988], Substantial numbers of miners worked in chrysotilc production: from the 1930s lo niid-19K(). roughly 1,000 lo 2.000 workers were employed in cliiysotile mining at any one time (personal communica tion. d Toil. NCOII. 1991 RdT 16.27). and alrout 2.600 in I960, which was 17% of asbestos miners. It seems unlikely from these data that scarcity of exposed workers is an adequate explanation for the absence of cases. Adequate dust control on cltrysotilc mines during the 1950s, 1960s. and 1970s is another fkissiblc reason, hut this is intuitively' Mesothelioma in South Africa 221 unconvincing. It is notable from Table VIH that (lie estimates of chrysolite miners arc disproportionately small relative to the tonnage mined and amphibolc miners. Different mining techniques may be one explanation. There are suggestive data that Southern African chryso lite contains relatively little ttemoliic [Rees cl al,, 19921, which may be an explanation for the paucity of chrysolite cases in the region. These data are preliminary, as they are based largely on a small study of lung fiber content of four ex-miners with asbestos-related disease and asbestos mining exposure exclusively in ehrysotilc mines. Confirmatory studies are required. ' . In summary, the great preponderance of crocidolite cases followed by atnosile and then ehrysotilc cases (in this study, no convincing case was identified) is consistent with the view that there is a fiber gradient in mesolhetiomagenic potential (crocidolite > amosite > ehrysotilc). This South African experience of a preponderance of crocidolite cases without convincing duysotilc cases may not be shared in countries with different asbestos mining and usage profiles (Smith and Wright, 1996|. Roggli and colleagues (1993] used scanning electron microscopy to examine fiber type in 9-1 cases of mesothelioma; aniositc was identified in SI9& of samples, ehrysotilc in 21%. and crocidolite in only l(i%.Thc authors conclude that tiic results do not support the notion that most mesotheliomas in the United Stales are due to crocidolite asbestos. The country of origin of the ehrysotilc might be a determinant of the relative contribution of each fiber type to country-specific case-loads. Lippman [1994] has summarized the mesothelioma yields in rat inhalation studies and round them to be highly dependent on fiber type. The percentage of mesotheliomas was 0.(i% (I /I f>9 rats) for Zimbabwean ehrysotilc, 2.5% (13/520) for the various ampliibolcs as a group, and 4.7% (9/193) for Quebec chrysolite. Supporting this view of a greater risk o[ mesothe lioma following ehrysotilc exposure arc reports of mesothe lioma in cases whose lungs contain chrysolite but no amphibolcs [Langcr and McCaughcy, 1982; Morirtga cl ah. 1989; Malioniet al.. 1990; Rogers c( ah. 1991). A nuniberof recently published studies of almost exclusively chrysotile- exposed workers have shown high risks of mesothelioma Raffn and colleagues J1993J reported on 269 men heavily exposed io asbestos and almosi exclusively io chrysolite. The relative risk for mcsotlicLionia was 22.73 for workers who had been employed at the facility for 20 or more years. Thus, findings in South Africa may need to he generalised Ollier settings with caution. pathologists, who were nagged for a couple of years. We relied on their goodwill and cooperation and were not disappointed. The South African Asbestos Tumor Reference Panel members supported the project by reviewing the diagnosis of mesothelioma. This article is based on a PhD awarded by the University of Cape Town* South Africa. REFERENCES Dean AD. Dean JA Burton JH. Dicier RC, 1990. EpL Info Version $. Atlanta; Center? for Disease Control. du Toic K. 1993. Ik number of persons exposed oa SA ehrysotilc mines. MuuKsbu^.NCOH.Rcpon Number RdT 16.27. Egret 1991- Revision 3- Sealje; Statistics and Epidemiology Research Corporation. Felix. MA, LcgCr IP. EMkii RJ. 1994. Three minerals, three epidemics -- Asbestos mining and disease in South Africa- In; Mchbun MA, Upton A, editors. The identification jkxI control of environmental and occupation diseases. Princeton: Princetoh Scientific Publishing, Ferguson DA. Beny G. Jeiihovsky T. Andreas SB, Rogers AJ. Fung SC, Grimwood A. Thompson R. 1987. The Australian mesothelioma survctl lance program 1979-1985. Med J Ausi H7:I66-I72. livi HP. 1988. Asbestos in South Africa. I 5 A/r Inst Min Metal 88:185-198. health and Safety Commission. 1979a. 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Asbestos. v<il. I. Properties,application and hazards. Belfast: Win Wiley & Sons. Mornuea K, Kohyama N. Sakuni M, Sasaki M. Tatcisbt R, Hara I. Told J, YoLovama K, Sourki Y, Sera Y. 1989. Asbestos fiber content of lungs with mesotheliomas in Ouka. Japan In: Uignon J, Peio R, Saraccr R. editor*. Non-occupjttonal exposure to mineral fibres, Lyon: lARC Sci Pub No 90. pp 4.18-443. acknowledgments hhelnds<in WJ, Pciket G. Seliknff II I9S7. Occupational exposure to axUivioi Populaiiiin ai risk and projected mortality 1980-2030. Am I |nri MeJ 1.259-311 " I>i Efic;t jjiiM-n w;i% (.he i'<jiuil(n;tl(>r ol flic {'oil Elizabeth siudy Center Gates were relciivd to this siinly l>y a Ijilv iMitnU-f til N'l'rih .Mnt'.tii [M.ieninifU'i5 jniinMv rariucggiani I. {editorj 1983. kncycrupacdia ul occupational health and sulciv 3rd <ievi^cdi*.'ditiui> Geneva. fincnuttonal LaNnu Office. ILiffti L. I.ynpc J:. Knrsfjard H 19*11 liu'tdt'ik'c of tarynpral cancel, luop t'jiicci .tiid iiiCMtHhclroma anniny j mhjIJcolhiil *4 jdn'Miis cement ViihI.l-is 2 22 Rees et al. almost exclusively exposed to duytoliic. Proceedings, Eighth iiucnwMiul Coofercnee on Occupational Lung Disease, Prague, OedtukiviUi. Prague: Cuch Medical Society. Rees D, to Toif RSJ, RmhU REG. van Siucrl GCH, Ruu DBfC 1992. TioboImc in Southern African duyrctile- S Afr J Sci 81:466-^69, Rogers Ai. Leigh J, Berry G. Fopwo DA, Mulder HB, Adad M-1991. Relationship between king asbestos fiber type and concentration and relative rol; of mesothelioma. ClAOu 67:1912-1920. Roggli VL, Pratt PC. Brody AR. 1993. Asbestos fiber type in malignant mesothelioma: An analytical scanning efecuoci microscopic study of 94 cases. Am Jlnd Med 23:60S-6M. Slade GF. 1931. The incidence of respiratory disability in worlds employed in asbestos mining, with special reference to the type ofdisability caused by the inhalation of asbestos dust. MD thesis. Johannesburg; University of the Witwatemand. Smith M. Naylor B. 1972. A method for extracting ferruginous bodies from sputum and pulmonary tissue. Am I Clin Pathol 58:250. Smith AIL Wright CO 1996. Ouytotile asbestos is (he main cause of pleural mesothelioma. Am I Ind Med 30:252-266. Scayner LT, Dirtfcovk DA Leroea RA. 1996. Occupational exposure ro ebsysotik asbestos and cancer risk: A review ofthe amphibolc hypothesis. Am J Public Health 6:179-186. Wagner JC. 1986- MesoOtelioma and mineral fibers. Cancer 57:1905-1911 2wi AB. Retd G. Landau SP, Kieliowski D, Situ F, BecUake MR. 1989. Mesothelioma in South Africa, 1976-64: Incidence and ease characteristics. Inti Epidemiol 18:320-329. APPENDIX Memory "Joggers" Read Out to Study Subjects 1. Have you ever been involved in any of (fie following? A. Insulation wort B. Working with furnaces C. Manufacturing asbestos cement products D. Working with boilers F_ Wearing heat protective cl orbing F. Selling asbcsios G- Construction site work H. Dentolisliing buildings I. Working in a factory using asbestos J. Working for tire navy/Mercham navy K. Repairing/servicing inoior vehicles more than once month L. Helping manufacture asbestos-containing articles M. Working in a power station N- Working with die manufacture of batteries O. Working in the plastic industry P. Using asbcsios rope or asbestos gaskets Q. Working in the rubber industry R Manufacturing brake linings or clutch plates S. Transporting asbestos T- Working for a railway company U- Insulation of hot water pipes V. Working with steam locomotives (train engines) W. Working wish sugar-cane 2. Did you ever work as a................. ? A. Boiler maker B. Fitter and/or turner C. Stevedore - P Marinc/civil engineer - II 1'lumbcr/plumbcr`s assistant F. Wcldcr/welder's assistant C. Building caipcnter/building carpenter's assistant U. Elccirician/dcclrician's assistant I. Faint manufacturer