Document KVYkygRLBBpv9w96qOzNKg50

FILE NAME Brakes BRK DATE 1970 Oct DOC BRK112 DOCUMENT DESCRIPTION Journal Article - Epidemiology of Primary Malignant Mesothelial Tumors in Canada 18 18 EXHIBIT NO .. No. + Betty Browning EPIDEMIOLOGY OF PRIMARY PRIMARY MALIGNANT age sex date and portem diagnostic MESOTHELIAL TUMORS IN CANADA A. D. McDONALD A. HARPER O. A. EL ATTAR AND J. C. MCDONALD formation obtain equal quality i minal illness sh undary lung cancer teria reasonably w advantage that se All fatal malignant mesothelial tumors known to pathologists in Canada between 1959 and 1968 were registered They numbered 165 1 per million population per annum two thirds were in males Occupational and residen- tial histories were obtained blind from relatives and friends of 90 of the were included but second main ques mesothelial tumor smoking in the san ides cases and 2 matched control series An association with definite or probable cer and for this 2 occupational exposure to asbestos was clearly demonstrated but only 20 of male cases and one female case had anyany such contact Almost all the excess was cases of this disease A field survey , at in the manufacture and industrial application of asbestos rather than in vestigators docto ete mining or milling No association was found with lesser degrees of occupa- and public health tional exposure ek or residence in asbestos areas but there was a small relatives and frien pleted we excess of possible domestic exposures The smoking historaiensd inuntlhiekemetshootsheelifoarl a detailed tumor and main control groups were almost identical French relating to cases of primary lung cancer direct household e tae, tory and smokin was given to the a des VIDENCE FOR AN ASSOCIATION BETWEEN MA- of Pathologists or the Quebec Association of apsanpioesssw ibelree allilste edm lignant mesothelioma and asbestos ex- Laboratory Physicians inquiring whether they fu of the exact natu semn posure rests mainly on the remarkable con- had seen any fatal cases of primary malignant relative was then ee centration of cases reported by Wagner et al.5 tumors of the pleura or peritoneum diagnosed volved contact w in the crocidolite mining areas of South Africa by autopsy or biopsy since 1959. In due conse conse n the control studies of Elmes et al.1 in Bel- we obtained a reply from them all and his cement copper check list was fast and Newhouse and Thompson2 in Lon- was in the affirmative a personal visit as had 1 don and the considerable excess mortality due made by one of us to review the records and subject ever to this disease observed by Selikoff et al. in to exclude cases which did not meet tliese which the pathologist had - following locomo ing overhauling American insulation workers The survey de- criteria or about doubt In all 165 cases were found large boilers or st scribed here was undertaken to obtain a more serious and mestic heating ec ne generally representative view of the problem 113 were pleural 45 peritoneal 3 pleural proofing fireproc diagnosis et in one of the 2 major chrysotile peritoneal and 4 pericardial The the bling prefabricate countries of the world Our aim has been to was supported by autopsy in two thirds of ta study all fatal cases known to have occurred cases and by biopsy in the remainder Later material from as many as ing buildings m or clutch plates in Canada since 1959 we plan to have ctw METHOD possible reviewed by a panel of pathologist During the visit to the pathologist 2 | tal control cases primary and one second- aT At the end of 1967 we wrote to the 423 ary lung cancer selected from the au- my members of either the Canadian Association topsy or biopsy records matched for sex and eret as closely as possible for age and date of adequately vo From the Department of Epidemiology and Health death In 2 instances no match- Epidemiology y 1960 1961 1962 Paper ay McGill University Montreal Canada A preliminary report on these results sented at the International Conference on was prePneumo- ing case of primary lung cancer could be found Two control series were chosen in or- 1963 1964 * taeda coniosis at Johannesburg in April 1969 der to examine 2 types of question Primarily reat Supported by a grant from the Institute of Occu- we wished to know whether persons who had pational and Environmental Health of the Quebec nary Asbestos Mining Association : died from malignant mesothelial tumors had enrat pevrat This survey was made possible by the great help differed in their past exposure to asbestos nd ow given us by pathologists and members of provincial and certain other materials from comparable cr other health departments throughout Canada We are Comparabil a also much indebted to all those who did the field sons in the general population 1 work and to the friends and relatives of the deceased ity demanded that the control series should for their cooperation Received for publication April 9 1970 comprise persons matched with the cases for 1965 1966 1967 1968( Incidenc 1960- 914 ciation of ether they nalizment liagnosed ue c ad 5 visi 3 e se ogist had e found zural and diagnosis rds of the er Later man 35 ogistogsists t: 1 2 sec 1 the au- sex and date of y match could be en in or- rimarily who had nors d estos 2 able r- apara . $ shotad case for No. 4 _ MALIGNANT MESOTHELIAl MESOTHELIAl MESOTHELIAl Tumors M. Donald et al 915 915 age sex date and place of death and post- mortem diagnostic procedure To insure that Nerminalinformation obtained from relatives would be equal quality it was important that the Nerminal illness should also be similar Sec- ondary ondary lung cancer seemed to meet these cri- teria reasonably well and had the additional advantage that several primary cancer sites primary were included but none were in the second main question was whether mesothelial tumors were related to lung A tobacco smoking in the same way as primary lung can- cer and for this reason a matched series of cases of this disease was also selected A field survey was arranged in which in- vestigators doctors public health nurses and public health inspectors sought out the relatives and friends of the deceased and com- pleted a detailed questionnaire in English or French relating to occupation residence in- direct household exposure to dust family his- tory and smoking habits Special emphasis was given to the occupational history So far as possible all employers or employing com- panies were listed with dates and a note made of the exact nature of the work done The relative was then asked whether each job involved contact with wood rubber asbestos cement copper nickel or fiber glass Finally a check list was used to inquire whether the subject had ever been employed in any of the following locomotive repair shop shipbuilding overhauling or breaking installation of large boilers or steam pipes insulation of do- mestic heating equipment building proofing fireproofing heat retention assem- bling prefabricated buildings and demolishing buildings manufacture of brake linings or clutch plates mining industry textile in- dustry cement industry dock or transport industry ' No interviewer knew to which group the case under investigation belonged and the information recorded in the questionnaire was also coded blind Questionnaires were completed for 447 % of the 493 cases and controls FINDINGS The distribution of cases by province and year of death is shown in Table 1 and by age sex and site in Table 2. More cases were found in 1966 and 1967 than in previous years Recent interest in these tumors may have contributed to this and as the records in some hospitals were poorer for the earlier years memory may also have been the factor With these points in mind the true rate of increase is difficult to assess During the 8 complete years 1960-1967 the average annual in- cidence was 1.0 per million of population The rate was appreciably higher in Quebec 1.5 than in Ontario 0.8 or in the rest of Canada 0.9 1966 and 1967 again account- quar- ing for much of the difference Three ters of the cases were aged 50 or more at death and males predominated by 2.4 to 1 Under 50 there was little difference in the sex distribution The case and 2 control series were very similar in age distribution and in the propor- tion of each for which the questionnaire was completed Table 3 Table 4 shows the number of men aged 18 years or more who were occupationally exposed up to 10 years before death to asbestos and certain other ma- terials in dust or vapor form Whereas all 3 TABLE 1. Distribution of Cases by Year of Death and Province Year . Year Ontario Ontario 1960 - 1961 1 1962 4 1963 9 ~ 1964 6 1965 1966 1967 1968 1st half 7 8 6 5 : 46 Incidence 1960-1967 0.8 1960-1967 Quebec 6 6 4 3 8 7 14 13 9 70 1.5 Other Provinces 9 3 5 7 3 5 9 6 2 49 0.9 Canada 15 10 13 19 17 19 31 25 16 165 1.0 a sap C rof - especially especialy se the insid te they they ng insd excs excess excess E ng q S te oy io cof Co Zo 7 ce a ie 7 a see jene of 40yedang 40yedang 40yedang 40yedang Lad e 3525 . i. ia L co ee woe = a mae vy <a u u : 1 1 Mesobeiral Mesobeiral Mesobeiral Mesobiral Mesobeiral < SOLD SOLD pot - e me cohcy 28. 24/20 24/20 24/20 as a omy Marignant Mrsomittat Tumors 6 McDonald McDonald et al 917 TABLE 4. Occupational Exposure of Men to Certain Materials Mesothelial tumors Secondary lung cancer Primary lung cancer ; Asbestos me Cement Copper Fiber glass Nickel Rubber Wood 100 men 20 17 4 62 63 52 31 18 1 96 men 3 90 10 0 0 0 19 0 97 men 4 80 10 0 0 0 16 0 Total exposures recorded 75 13 32 0 29 0 * Definite or probable exposure to the substances named in dust or vapor form in men aged 18 or more The sumber of men who were also definitely or probably exposed to asbestos is given in parentheses SEC or prot 1 Tal ie manu ings or of th or mill e difer re sta it men job for 26. 26 ing wood for which there was evidently no difference between the 3 groups 37 exposures to cement copper fiber glass nickel or rub- ber were recorded for the cases of which 12 were in men definitely or probably exposed to asbestos The 25 remaining exposures were in 19 men and the comparable figures for the 2 control groups were 10 and 9 respectively An analysis of these exposures is shown in Table 7 where it may be seen that the excess appeared to be in occupations involving contact with copper nickel fiber glass or rubber 9 rather than with cement only and seemed unrelated to possible exposure to asbestos The relevant occupations of the 9 men in the mesothelial group were as follows . copper lathe operator 2 munition manu- facture brass foundry nickel lathe operator 2 mine worker rubber tire manufacture plantation work fiber glass municipal maintenance work caulking ship Residential histories indicated that 45 of male cases and 38 of female cases had spent their childhood entirely in a rural area compared with 40 of males and 38 of females with secondary lung cancer but the primary lung cancers were less often reared in rural areas males 31 females 28 No differ- ence was found between cases and both con- trol groups after the age of 15 years Exclud- ing 5 cases 3 mine or mill workers and 2 textile workers and one mine and mill worker in each control group who lived in mining towns only 3 men and 2 women had deserve en had Exclud imary cancer 1 TABLE 5. Males Distribution of Cases and Controls According to Their Occupational Exposure to Asbestos Mesothelial tumors Secondary lung cancer Primary lung cancer Exposure to asbestos Definite . . : ; Probable Possible Unlikely All No. i1 9 20 60 100 % 20.0 20.0 60.0 100.0 No. 1|* 2 22 71 96 % 3.1 22.9 74.0 100.0 No. % _ 1 4.1 3 16 16.5 77 79.4 97 100.0 P Males Distribution of definite and probable groups compared with possible and unlikely x= 21.5 2 d.f. Females Mesothelial tumors Secondary lung cancer Primary lung cancer Exposure to asbestos a Definite { Probable Possible Unlikely No. % 1 2.0 49 98.0 No. _ _ 1 51 % 1.9 98.1 No. % _- _ 46 100.0 All 50 100.0 52 100.0 * One child in each group dying under the age of 18 has been excluded 46 100.0 aa, Mate, 6 ETE IREe e IFee Se ed 7a ar af 2s ae Ae ae IEcpiseny A Nl Be er A lee a 918 CANCER October 1970 : LABLE 6. Distribution of Occupations Classified Under Definite or Probable Exposure to Asbestos Mesothelial tumors Asbestos mine or mill 3 Asbestos textile manufacture 4 Brakelining installation 2 Insulation 5 Other occupations involving materials 5 contact with insulation materials 5 Hardware store handling asbestos sheet and pipe 1 Filled gas masks with asbestos textile t lung Secondary lung cancer Primary lung cancer 1 1 0 0 0 0 0 . 2 3 .0 0 - 0 0 TOTAL 21 3 4 . * Includes one person who worked in brakelining manufacture Ve 26 ~ ever lived within 20 miles of an asbestos mine One of the 5 was a case 3 had secondary lung cancer and one had primary lung cancer The possibility of contact as a result of some other member of the family bringing home dusty clothes from occupations involving the use of asbestos was also examined Ex- cluding 7 persons 5 cases and one in each control group who were occupationally exposed themselves definitely or probably there was one case in a female with definite home exposure and one male with probable home exposure In addition to 5 persons one case and 4 with primary lung cancer who were possibly occupationally exposed to asbestos themselves there were 26 persons with a possible home exposure 14 cases 6 with secondary lung cancer and 6 with primary lung cancer The category of possible home exposure was given in households where a person possibly exposed at work to asbestos brought home dusty clothes Thus excluding those persons with definite or probable occupational exposure there were 15 persons with mesothelial tumors 8 with secondary lung cancer and 10 with primary lung cancer who had had at least possible home exposure to asbestos dust The frequency of cancer reported in cl se relatives did not differ from that in the . . trol groups An analysis of cigarette smok habits is shown in Table 8. In both males and females persons in the primary lung cancer group had smoked considerably more than those in either the case or secondary lung cancer groups The latter 2 groups had almost an identical distribution of smoking habits The 20 men with definite or probable occupational exposure to asbestos showed no great difference in smoking habits from cases without occupational exposure DISCUSSION Though our study is not directly compa- rable with those of Elmes et al.,,in Belfast and Newhouse and Thompson2 in London it seems fairly clear that the difference between cases and controls regarding asbestos exposure was less in our findings than in theirs There are several possible explanations for this The first is that our study was based on a mational sample of cases derived from all p s of a very large country whereas theirs we we from 2 specific industrial areas one a ship- building city and the other from a hospital close to a large asbestos factory A second TABLE 7. Occupational Exposure to Certain Materials of Men without Definite or Probable Exposure to Asbestos Cement only Copper nickel rubber or fiber glass Mesothelial tumors 10 5 Secondary lung cancer 96 Primary lung cancer 82 92 11 10 19 7 10 7 * Including three men also exposed to cement The number of men possibly exposed to asbestos is given in parentheses 92 30 or mor TOTAL * Excludin possibility cases which third poin sure that were collec of the gro was not so possible i Thompson not compa gation was selected fo on popul It was n bestos in t Several stu exposure | risk of this our series to match and geogr considered less it was worth noti ~ asbestos w .. lung cance . in the caus cancers wa 3s The fin dicate that _~ 1. Elmes 0. .: Diffi asbestos Bri _ 2. Newhou lioma of ple asbestos in 261-269,1 261-269,1 3. Selikoff Vol 26 in cl ' the co smoking th males ary lung bly more .econdary oups had smoking probable lowed o om cas - compaIfast and ndon it between exposure rs There for thi on all part eirs were e a shiphospital \ second No. 4 : MALIGNANT MESOTHELIAL TUMOR McDonald McDonald et al 919 : x 7 ad *3 Cigarettes per day . Nil 10 or less 11-29 30 or more TABLE 8. Average Daily Number of Cigarettes Smoked Male Female Mesothelial tumors 21 22 17 18 40 41 19 20 Secondary lung cancer 19 20 21 22 37 30 18 19 Primary lung cancer Mesothelial tumors with asbestos exposure t+ 10 11 47 50 34 36 2 10 + 20 13 65 1 5 Mesothelial Mesothelial tumors 29 58 9 18 10 20 2 + Secondary lung cancer 36 71 5 10 7 14 6 Primary Primary lung cancer 21 +7 9 20 12-27 12-27 3 7 TOTAL 97 100 95 100 95 100 20 100 50 100 51 100 45 100 * Excluding 6 persons under 15 years of age and 6 men and 2 women whose smoking history was not recorded possibility is that our series was diluted by cases which they would not have accepted A third point is that we took great care to in- sure that the histories of case and control were collected and coded without knowledge of the group to which they belonged This was not so stated in the Belfast survey and not possible in the study of Newhouse and Thompson The findings of Selikoff et al.are not comparable with ours since their investigation was based on an occupational group selected for its exposure to asbestos and not on a population sample It was not our aim to assess the role of as- bestos in the etiology of primary lung cancer Several studies have shown that occupational exposure may be associated with increased risk of this tumor especially in smokers Since our series of primary lung cancer was selected to match the mesothelial cases in age sex and geographical distribution it cannot be considered representative in itself Neverthe*. less it was probably sufficiently so for it to be worth noting that the history of exposure to asbestos was very similar to that for secondary lung cancer Any contribution from asbestos in the causation of this series of primary lung cancers was therefore not apparent CONCLUSION The findings from this national survey indicate that primary malignant mesothelial tu- mors are rare in Canada and it is somewhat doubtful whether there has been a true in- crease in incidence since 1959. An association between these tumors and definite or probable occupational exposure to asbestos was clearly demonstrated but only a minority of male cases 20 and one female case had any such exposure No difference was found between cases and the 2 control groups re- garding lesser degrees of occupational exposure or residence in asbestos areas but in % of the mesothelial tumors compared with % of the secondary lung cancer group there was at least a possible domestic contact with asbestos dust Probably our most noteworthy finding was that almost all the excess in occupational exposure was in the manufacture and indus- trial application of asbestos rather than in mining or milling Taken in conjunction with the results of other epidemiologic studies this suggests either that chrysotile is less associated with mesothelial tumors than other forms of asbestos or that something in addi- tion to asbestos is necessary If there is an additional factor our findings imply that it is not cigarette smoking Nine men with mesothelial tumors had worked in occupations unrelated to asbestos but involving contact with copper nickel rubber or fiber glass compared with one in each of the control groups The interpretation of this finding is doubtful REFERENCES 1. Elmes P. C. McCaughey W. T. E. and Wade 0. .: Diffuse mesothelioma of the pleura and asbestos Brit Med J. 850-353 1965 2. Newhouse M. L. and Thompson H Mesothelioma of pleura and peritoneum following exposure to asbestos in the London area Brit J. Industr Med 261-269 1965 3. Selikoff I. J. Churg J. and Hammond E. C Relation between exposure to asbestos and mesotheli- oma New Eng J. Med 560 5615965 4. Selikoff I. J. Hammond E. C. and Churg .: Asbestos exposure smoking and neoplasia JAMA 106-112 1968 5. Wagner J. C. Sleggs C. A. and Marchand P Diffuse pleural mesothelioma and asbestos exposure in the north western Cape Province Brit J. Industr Med 260 2711960