Document a6wBdxz648wGVXjLx9RjyQxM

No -t EPIDEMIOLOGY OF PR 1 MARY MAI.ICNANT age. sex, < mortem di MESOTHELIAL TUMORS IN CANADA* ^ informntic of equal t \. D. McDonald, A. Harpf.r. O. A. Ft. Attar. and J. C. McDonai.p terminal i ontlary hit leiia renso advantage All fatal malignant mesothelial (union Inmni (o pathologists in Canada be(wren ID'iD and mid-l!)(iS were registered- They munhrvcd 1G5 (1 per millinn population per annum); two thirds were in males. Occupational and residen tial histories were obtained "blind" from tclatives and friends of OOCV; of the were inclu second mn mesothelia smoking in cases and 2 matched control series. An association with definite or probable occupational exposure to asbestos was clearly demonstrated, but only 207c of male eases and one female case had any sitrl' contact. Almost all the excess seas in the manufacture and industrial application of asbestos rather than in m in in" or milling. No association was found with lesser degrees of occupa tional exposure or residence in asbestos-mining areas, but there was a small excess of possible domestic exposures. The smoking histories in the mesothelial tumor and main control groups were almost identical and unlike those for cases of primary lung cancer. ccr. and, h eases of the field : vestigators and public relatives an pleted a dc Fiench rel: direct lions tot and : was given t VItlFNCF. FOR AN ASSOCIATION IIFTWTFX MA- E lignnnr. mesothelioma atul asbestos ex posure rests mainly ?m the remarkable con centration of cases repot ted by Wagner et al.5 in the crocidolitc mining areas of South Africa, the case-control studies of Elmes et al.1 in Bel fast. and Ncwhousc and Thompson2 in Lon don. ami the considerable excess mortality cine to this disease observed by Selikolf et al.2 in American insulation workers. The survey de scribed here was undertaken to obtain a more generally representative view of the problem in one of the 2 major chrvsotilc-producing countries of the world. Our aim has been to study all fatal cases known to have occurred in Canada since 1059. nf Pathologists or the Out:bet Association of I.aborntorv Physicians inquiring whether they bat! seen any fatal cases of primary malignant tumors of the pleura or peritoneum diagnosed bv autopsy or biopsy since 1939. In due course we obtained a reply from them all. anil, if this uas in the nfTinnativc, a personal visit was made by one of us to review the records anti to exclude cases which did not meet ihese cti'eria or about which the pathologist had serious doubt. In all, 1G5 eases were found: 1 I I were pleural. -15 peritoneal. " plemal and peritoneal, and -1 pericardial. The diagnosis was supported bv autopsy in two thirds nf the cases and by biopsy in the remainder. Later, we plan to have material from as many as ' ; | * J | I ' | * as possible, panics were of the exat relative wnvot d com cement, cop a t heck list subject hat' foie wing: i ing. overhat large boilci m sr.c henti proofing, fu bling prefa! ing buildin or clutch pi possible reviewed by a panel of pathologists. ' Mf.tiiod At the end of 1007 we wrote to the -120 members of either the Canadian Association During the visit to the pathologist. 2 fatal control eases--one primal y and one secondatv lung cancer--were selected from the antojisv or biopsv records, matched for sex and. 1-iom die lVpaitmi t of Epidemiology and Health, McC'.ili l nivt-iMlv, Mnmvc-ai. Canaria. * A (neliiiiinaiv ieport nn ibr-c results was pre sented at the Internalional Conference on PneumoCnuiosis at Jobaniu-biiig in .April, I9t)9. Smipniictl bv a grant horn the Institute of Occu pational and F.nviinumeiilnl Health of the Out-bee Asbestos Alinin'a A-mii iation. "I 11 is survey was made possible lu the glint help given us by pathologists anti ineinliers of provincial and oilier health departments tlirniighniit Canada. A\'e arc also much indebird to all those who ditl the held work and to the Mends and relatives of the deceased for their cnoperalion. Received for publication April 9, 1970. as closely ns possible, for age and date nf death. In 2 instances, no adequately match ing case of primnrv lung cancer could be round. Two control series were chosen in or der to examine 2 tvpcs of question. Primal ily. we wisiicd to know whether persons who had (1 i -1 from malignant mesothelial tmuois had did'cml in their past exposure to asbestos and certain other materials from comparable per sons in the general population. Comparabil ity demanded that the control series should comprise persons matched with the cases for , 1 i r Inci' No. 4 Malignant Mfsotukual Tumors McDonald ct al. !ii:> age. sex, (Into and j>Iru.c of death, and post mortem diagnostic procedure. To insure that information obtained from relatives would he of equal quality, it was important that the terminal illness should also he similar. Sec ondary hot" cancer seemed to meet these cri teria reasonably well and had the additional advantage that several printarv cancer sites were included, but none were in the lung. A second main question teas whether primalv mcsoihclial tumors were related to 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 in volved contact with wood, rubber, asbestos, cement, copper, nickel, or fiber glass. Finally, a check list teas used, to inquire whether the subject had ever been employed in any of the following: locomotive repair shop: shipbuild ing, overhauling, or breaking: installation of large boilers or steam pipes: insulation of do mestic heating equipment; building--sound proofing, fireproofing, heat retention, assem bling prefabricated buildings, and demolish ing buildings: manufacture of brake linings or dutch plates; mining industry: textile in- dustry; < cment industry: duck or transport industry. No inlet'viewer knew to which gioiqr..the case under investigation belonged, ami the information recorded in the questionnaire was a ho coded blind. Questionnaires were completed for -M7 (91%) of the )!>.'! cases and control Finuings Tin 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 1906 and 1907 than in previous years. Recent interest in these tumors may have contributed to this, and, ns the records in some hospitals were poorer for the earlier years, memory may also have been a factor. With these points in mind, the true rate of increase is difficult to assess. During the 8 com plete years, 1960-1967, the average annual in cidence was 1.0 per million of population. The rate teas appreciably higher in Quebec (1.5) than in Ontario (0.8) or in the rest of Canada (0.9), 1966 and 1967 again account ing for much of the difference. Three quar ters of the cases were aged 50 or more at death, and males predominated by 2.1 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 (Tabic 5). 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 ?. Table 1. Distribution of Cases by Year of Death and Province Year Ontario 1960 1961 1962 1963 1964 1965 1966 1967 1968 (1st half) - 1 4 9 6 7 8 6 5 --46 tciclence/miMion/yenr 1960-1967 0.8 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 Canaria 15 10 13 19 17 19 31 25 16 -- 165 1.0 010 Aye (yea rs) 0 10 2050 4050 <;o70 so- All Total Cancer October 1070 Tabu: 2. ricnr.i Distribute Ml of Mce<olhclial Tumors by Ajje, .Sex. and.Site Peritoneum Pleura and peril'11101101 Pericardium T.ual _ M FMFMFMFM F 11 } 1= -- ------ 2 1 4t 7 4 1 1 -- -- -- 1 .3 () <> 7 4 t -- -- -- 1 !3 *) IS 5 1) 1 1-- 1 1 51 s >0 5 > 5-- 2 -- -- 2S 12 15 5 7 6 -- -- -- -- 22 11 34 i 1 -------- 4 5 SO 33 26 19 1 2 1 3 108 57 113 45 5, 4 165 Vol. L'(i groups were equally exposed to wood dust, relatively mote men in the mesothclial tumor group were exposed to all tire other materials, the greatest excess being for asbestos. Men who were exposed to asbestos tended also to be exposed lo other materials, especially ce ment' and fiber glass (Table d), but these were only responsible for part of the excess exposure to the other materials. The excess of "definite" or "probable" exposure to as bestos (Table 5) in the mesothclial tumor group compared with both control groups was substantial (P < .001), but there was vir tually no difference in the frequency of jobs in which exposure was classified as "possible." In 00% of the cases, however, occupational exposure to asbestos was considered "un likely." Only 2 women in all had any occupa tional exposure to asbestos; there was a definite exposure in the mesothclial tumor group and a possible exposure in the second ary lung cancer group. 'rhe occupations involving definite or probable exposure to asbestos are listed in Table (>. Men employed in asbestos textile nianufacturc, the installation of brake linings, or a* insulators were responsible for most of the excess of cases over controls. Mine or mill workers made little contribution to the differ ence, and only one person, a hardware storeman, had worked with asbestos-cement prodnets. The time between first exposure and death for the 21 cases in the definite or piobablc class ranged from Ifi to af) years; I men and one woman who worked on the job for less than 1 years had intervals of IS, 2fi. 2f>, 29. and 3a years. Materials oilier than asbestos also deserve {\uthcr consideration since several men had worked with more than otic of them. F.xilud- , y i , t ,,j j < ' Table 3. Distribution by Age and Sex of Cases and Controls Males Females Ace 010203040506070- so - Mesothclial tumors 2 (2) 8 (8) 13 M0) 31 (31) 27 (25) 23 (22) 4(3) Secondary luns cancer i (i) 2 (2) 6(6) 14 (11) 26 (22) 35 (32) 20 (19) 4 (4) Primary Inner enneer 1 (0 2(21 24 (20) 24 (2.5) 35 (3 5) 17 (15) 4 (4) Mesothclial tumors i di Hu 4 (3) 6 (6) 9 (8) 8 (7) 12 (11) 11 (10) 5 (4) Secondary hm cancer i (a 2 (2) 6 (5) 10(10) 7 (7) 15 (14) 13 (11) 3 (5) All Mean sr> 10,S (101) 58.7 13 9 108 (97) 59. 1 13.3 107 (9S) 59. 1 12.5 No. of questionnaires completed shown in parentheses ( ). 57(51) 55. S 19.3 57 (55) 57.4 17.3 Trim ary Inner <mncer i a) 3 1 2) 1 t (13) 8(71 12(7) ' 15(15) 3 (2) . 56 (471 58 8 15 5 No. 4 Asl Cei Co, Fil Nil Ru Wo Tot * Definite oi number of men ing wood, h difference bt to cement, c ber were rec were in met to asbestos. * in 19 men, a 2 control gn An analysis Table 7, win a p [reared to tact with co| (9:1:1) rathe seemed unn bestos. The r in the mes. copper: latln Table 5. Maies Kxposure i Den. Pro! PosUnH! All Males: Di-' P < 0.001 Females Exposure Ow. I'r . Pol"nb All" * One child i 'I -1' ' N. I M.u.iu.vant Mesothki.iai. Tumoks McDonald el til. 917 :\sbc>(OS Cement Copper Fiber Nickc! Rubber Wood I'aru: 4. Occupational Exposure of Men to Certain Materials* Me.soihelial tumors Se oik!arv lumi cancer Primary lumj cancer (100 men) 20 17(4) 6 (2) 6 (3) 5 (2) 3 (1) 18(1) (tv, men) 3 > (0) 1 (0) n 0 i) to (0) (97 men) 4 8 (0) 1 (01 0 0 n 16 (0) 'Total exposures recorded 75 (13) 32 (0) 29 (0) * Definite or probable exposure to the substanres named in dust or vapor form in men aged 18 or more. The number of men who were also definitely or probably exposed to asbestos is given in parentheses. ing wood, for which there was evidently no facture, brass foundry; nickel: lathe operator tmd- | difference between the 3 groups, 37 exposures (2), mine worker; rubber: tire manufacture, to cement, copper, fiber glass, nickel, or rub plantation work; fiber glass: municipal main prob- ber were recorded for the cases, of which 12 tenance work, wood-caulking (ship). were in men definitely or probably exposed Residential histories indicated that 45% of intfu- !- to asbestos. The 25 remaining exposures were male cases and 38% of female cases had spent s or in 19 men. and the comparable figures for the their childhood entirely in a rural area com2 control groups were 10 and 9, respectively. paied with -10% of males and 38%, of females >f the An analysis of these exposures is shown in with secondary lung cancer, but the primary mill Table 7. where it may be seen that the excess lung cancers were less often reared in rural :i(Tcr- appeared to be in occupations involving con areas (males 31%,, females 2S%). Xo differ torcI nod- tact with copper, nickel, fiber glass, or rubber ence was found between cases and both con (9:1:1) rather than with cement only, and trol groups after the age of 15 years. Exclud and seemed unrelated to possible exposure to as ing 5 cases (3 mine or mill workers and 2 ; uob- bestos. The relevant occupations of the 9 men textile workers) and one mine and mill incn !> for in the mcsothclinl group were as follows: wotker in each control group, who lived in copper: lathe operator (2), munition manu mining towns, only 3 men and 2 women had 2G, -erve had dud- 1 T.VIU.E 5. Distribution oDCases and Controls According t > Their Occupational Exposure to Asbestos Males Mesothelial tumors Fee- mdary 1 ung cancer Primary luiijj cancer Exposure to asbestos Xo. % Xo. % Xo. C/of ..... 'V ver 1 i 1 1 H i Definite Probable Possible Unlikely All* 1 9J 20 60 100 20,0 20 0 60.0 100.0 'I 3.1 2j 22 22.9 71 74.0 96 100.0 '! 3.1f 4.1 16 16 5 77 79.4 97 100.0 Males: Distribution of definite and probable groups comp;* f,(\ with possible and unlikely: = 21.5. 2 d.f.. P < 0.001 I ;i Females Mcsotheli d tumors Secondary bine cancer Primary lung cancer i. DI ! 1 Exposure lo asbestos Definite Probable Possible Unlikely No. i -- -- 49 0/70 2.0 08.0 Xo. -- -- 1 51 O/0f 19 98 1 Xo. -- '-- -- 46 % 100 0 1 All* so 100.0 52 100 0 4 * One child in each group (lying tinder the age of 18 has been excluded. 46 100 0 .No. I Mai k:\ant Mesotim.i iai. I t mors M<Donald <:t til. 919 T.\nt.r. S. Average Daily Number of C iearettcs Smoked Male Female Cigarettes per day Nil 10 or less 11-20 or more Mesothclial tumors . 21 ? > 17 IK 40 41 10 20 Secondary lung cancer 10 20 21 22 a 7 .10 IS 1<> Primary lung cancer Mesothclial tumors with asbesin* exposm 44 to It 47 so .U 56 2W 4 20 1.5 65 15 Me.-utheliai tumors 20 ss 0 IS 10 20 24 Secondary Primary Innc ennrer lime: cancer .56 71 . 21 47 5 10 o 20 7 14 12 27 .5 h a7 .Total* 97 too <>5 WO 05 mo 20 WO 50 100 51 loo 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.3 are not comparable with ours since their investi gation 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.4 Since our scries of primary lung cancer was selected to match the mesothchal 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 in dicate that primary malignant mesothclial tu mors are tare 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 prob able 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 expo sure or residence in asbestos-mining areas, but, in 10% of the mesothclial tumors com pared with 5% 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 exposuie was in the manufacture and indus trial application of asbestos rather than in mining or milling. Taken in conjunction with tlm lesults of other epidemiologic stud ies, this suggests either that chrysotilc is less associated with mesothclial 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 mesothclial 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 interpreta tion of this finding is doubtful. REFERENCES 1. Elrncs. P. C,, McCaughcy, W. T. E., and Wade. O. L.: Diffuse mesothelioma of the pleura and asbestos, ririt. Med. J. 1:350-353, 1005. 2. Newhouse. M. I... and Thompson, II.: Mesothe lioma of pleura and peritoneum following exposure to asbestos in the London area. Brit. J. Industr. Med. 22-.2G1-2G9, 10(15. 3. Selikoff, I. J., Churg, J.. and Hammond, E. C.: Relation 1'olwccn exposure to asbestos and mesotheli oma. New ling. J. Med. 272:5(10-5(15, I9G5. 4. Selikoff, I. J., Hammond, F.. C,, anti Churg. J.: Asbestos exposure, smoking and neoplasia. JAMA 201:100-112, 1'ltiR. 5. Wagner, J. C,, Sleggs. C. A., and Marchnnd. I'.: Diffuse pleural mesothelioma anil asbestos exposure in the north western Cape Province. Brit. J. Industr. Med. 17:2(10 -271, 1900. -