Document 0q6R4e41MYZk8Bq6JX6w3Vkbb

P . -- . - - "ii--iittiiBf fraiilir'--*--l**,'-i-*f-- /> J M _ M W - ? / ? ftW aiflBiMrfete So. 4 EPIDEMIOLOGY OF PRIMARY MALIGNANT joe. sex, date and mortem diagnostic MESOTHELIAL TUMORS IN CANADA* information obtair of equal quality, A. D. M c D o n a l d . A. H a r p e r . O. A. E l A t t a r , a n d J. C. M c D o n a l d t-rminal illness sh ondary lung cancel tcria reasonably tv- advantage that se- All fatal m alignant m esothelial tum ors know n to pathologists in C anada be tw een 1959 a n d mid-196S w ere reg istered . T h e v n u m b e re d 165 (1 p e r m illio n p opulation p er annum ): two thirds w ere in males. O ccupational an d residen were included, but second main quesi mesothelial tumor tia l histo ries w ere o b ta in e d `'b lin d " fro m relativ es a n d frie n d s o f 90FJ o f th e smoking in the sam cases and 2 m atched control series. A n association w ith definite or probable cer, and, for this r occupational exposure to asbestos was dearly- dem onstrated, b u t onlv 20fo of m ale cases an d one fem ale case h ad any such contact. Almost all the excess was in the m anufacture and industrial application of asbestos rath er th an in m ining o r m illing. N o association was found w ith lesser degrees of occupa tional exposure or residence in asbestos-mining areas, bu t there was a sm all excess of possible domestic exposures. T h e sm oking histories in the m esothelial tum or and m ain control groups were alm ost identical and unlike those for cases of prim ary lung cancer. cases of this disease A field survey v vestigators (doctor and public health relatives and friend pleted a detailed q French relating to direct household ex torv, and smoking was given to the oc Evidence for a n association betw een m a - of Pathologists or the Quebec Association of Iignant mesothelioma and asbestos ex Laboratory Physicians inquiring whether thev posure rests mainly on the remarkable conh ad seen any fatal cases of primarv malignant as possible, all emp panies were listed w of the exact nature centration of cases reported by AVagner et al.5 tumors of the pleura or peritoneum.diagnosed relative was then as in the cxocidolite mining areas of South Africa, by autopsy or biopsy since 1959. In due course volved contact wit! the case-control studies of Elmes et al.1 in Bel we obtained a reply from them all. and, if this cement, copper, nicl fast, and Xewhouse and Thompson2 in Lon was in the affirmative, a personal visit was a check list was use don, and the considerable excess mortality due made by one of us to review the records and subject had ever bee to this disease observed bv Selikoff et al.3 in to exclude cases which did not meet these following: locomoth .American insulation workers. The survey de criteria or about which the pathologist had ing, overhauling, or scribed here was undertaken to obtain a more serious doubt. In all, 165 cases were found: large boilers or steal generally representative view of the problem 113 were pleural, 45 peritoneal. 3 pleural and j mestic heating equi in one of the 2 major chrysotile-producing peritoneal, and 4 pericardial. The diagnosh j proofing, fireproofin countries of the world. Our aim has been to was supported by autopsv in two thirds of the ] bling prefabricated study all fatal cases known to have occurred cases and by biopsy in the remainder. Later, ing buildings; mam in Canada since 1959. we plan to have material from as many as or clutch plates; mi possible reviewed by a panel of pathologists. M ethod During the visit to the pathologist, 2 fatal control cases--one primarv and one second At the end of 1967 we wrote to the 423 ary lung cancer--were selected from the au members of either the Canadian Association topsy or biopsy records, matched for sex and, Year fro m t' e Departm ent of Epidemiology and Health, McGill L n:'.er-:t*.. Montreal. Canada. * A prehrr.m ar. report on the-e result, was pre- s-med at t/.e International Conference on Pneum o- cornoMs at Johanne-bor^r in A pril. I960. S u p p o r t e d hr. a snarit f ro m t h e I n s t i t u t e o f O c c u pational ar.d Ensironrnental H ealth of the Quebec A -be-tos Mmir.-r A --o c i a t i o n . " I b i s -ur.c-s u a s m a d e poss ible b-. t h e g r e a t h e l p 2 A e n us b-. p a t c o ! o c b - o a n d m e m b e r s of p r o v in c ia l a n d o-her health departments throughout Canada. We are a. o m uc h indebted to all there who d id the field work and to t ie friends and relatives of the deceased for tiic-ir r o e r i o n . K e c e n e d for p u b licatio n A pril 9, 1970. as closclv as possible, for age and date of death. In 2 instances, no adequately match ing case of primary lung cancer could be found. Two control series were chosen in or der to examine 2 txpes of question. Primarily, we wished to know whether persons who had died from malignant mesothelial tumors had differed in their p>ast expiosure to asbestos and certain other materials from comparable per sons in the general population. Compiarability demanded that the control series should comprise persons matched with the cases for 1960 1961 1962 1963 1964 1965 1966 1967 1968 (1st h In cidence/m il 1960-1967 914 .mnjmnyygiiji HHfB.imtxmyn. n -in*1 X No. 4 M al ig n a n t M so t h l ia l T lm ors McDonald et al. 915 T age, sex, date and place of death, and post dustry; cement industry; dock or transport mortem diagnostic procedure. To insure that industry. information obtained from re-lathes would be No interviewer knew to which group the of equal quality, it was important that the case under investigation belonged, and the AIJJ terminal illness should also be similar. Sec information recorded in the questionnaire ondary lung cancer seemed to meet these cri was also coded blind. Questionnaires were teria reasonably well and had the additional completed for 447 (91%) of the 493 cases and advantage that several primary cancer sites controls. be were included, but none were in the lung. A Iion second main question was whether primary den- mesothelial tumors were related to tobacco F indings ib e smoking in the same way as primary lung can The distribution of cases by province and ab le cer, and, for this reason, a matched series of vear of death is shown in Table 1, and by age, of cases of this disease was also selected. sex, and site in Table 2. More cases were vas i in A field sur-vcv was arranged in v, Inch in found in 1966 and 1967 than in previous vestigators /doctors, public health nurses, vears. Recent interest in these tumors may upam al lelial for and public health inspectors) sought out the have contributed to this, and, as the records relatives and friends of the deceased and com in some hospitals were pxaorer for the earlier pleted a detailed questionnaire in English or vears, memory may also have been a factor. French relating to occupation, residence, in With these points in mind, the true rate of direct household exposure to dust, family his- increase is difficult to assess. During the S com torv, and smoking habits. Special emphasis plete years, 1960-1967, the average annual in was given to the occupational historv. So far cidence was 1.0 per million of population. Association of g whether thev nan,' malignant leum diagnosed 1. In due course all, and.Jf this sonal visit seas .he records and aot meet these aathologist had es were found; 1. 3 pleural and The diagnosis >vo thirds of tlie mainder. Later, >m as manv as . as possible, all emplovers 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 was used, to inquire whether the subject had ever been emploved 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 clutch plates; mining industry; textile in- 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 ing for much of the difference. Three quar 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 pathologists. j iiologist, 2 fatal nd one second 'd from the auted for sex and, ;e and date of rquatelv matchnicer could be re chosen in or ation. Primarilv, ersous who had lial tumors had to asbestos and , Table 1. Year 1960 1961 1962 1963 1964 1965 1966 1967 196S (1st half) Distribution of Cases by Year of Death and Province O ntario Quebec O th er Provinces Canada - 6 9 15 1 6 3 10 4 4 5 13 9 3 7 19 6 8 3 17 7 7 5 19 8 14 9 31 6 13 6 25 5 9 2 16 romparable pern. Comparabilol series should th the cases for 4 i { 46 70 49 Incidence/million /vear 1060-1067 O S 1.5 0 .9 165 1.0 916 Cancer October 1970 Table 2. Pleura Ace ( years t Ml F 0- -- 10- > 20- -- 30- 7 40- 9 50- IS 60- 26 7 0 - 15 SO- 3 -- 1 4 4 4 3 5 5 4 All so 33 Distribution of M esothelial Tumors by Ago. Sex. and Sire Peritoneum Fleura jnd peritoneum Pericardium Total MFMFMFMF -- 1-- -- ---- -- 1 ---- -- -- -- 1 -- -- -- -- ---- -- 4 1 1-- -- -- 1S6 4 1-- -- -- 1 13 9 11 4 1 -- 1 1 31 S 2 5-- 2-- -- 28 12 7 6 -- -- -- -- 22 11 i 1-- -- ---- 45 26 19 1 2 1 3 108 57 T otal 115 45 3 4 165 ' ol- '-N groups were equally exposed to wood dust, relatively more men in the mesothelial tumor group were exposed to all the other materials, the greatest excess being for asbestos. Men who were exposed to asbestos tended also to be exposed to other materials, especially ce ment and fiber glass (Table 4b 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 3) in the mesothelial tumor eroup compared with both control groups Was substantial (P < .0011, but there was vir tually no difference in the frequency of jobs in which exposure was classified as "possible." In 60% of the cases, however, occupational exposure to asbestos was considered "un likely." Onlv 2 women in all had any occupa tional exposure to asbestos; there was a definite exposure in the mesothelial tumor group and a possible exposure in the second ary lung cancer group. The occupations involving definite or prob able exposure to asbestos are listed in Table 6. Men employed in asbestos textile manu facture, the installation of brake linings, or as insulators were responsible for most of the excess of cases over controls. Mine or mill workers made little contribution to the differ ence, and onlv one person, a hardware store man, had worked with asbestos-cement prod ucts. The time between first exposure and death for the 21 cases in the definite or prob able class ranged from 16 to 50 years; 4 men and one woman who worked on the job for less than 4 vears had intervals of 18, 26, 26, 29, and 33 years. Materials other than asbestos also deserve further consideration since several men had worked with more than one of them. Exclud- T able 3. D istribution by Age ar.d Sex of Cases and C o n tr o l M aies F em ales M eyjthei'ip Jcetscdarv Primr-.- M esotheli Secondarv Age tumors lun? cancer lung cancer tumors lung cancer 0- i a) i (i; i a) i O) 10- 2 (2) i d) 20- 2 {2) 4 O) 2 f2) 30- 8 (S) 6 (6) 2 (2 , 6 (6) 6 f5) 40- i3 n o ) 14 M l) 24 '20) 9 (S) 10 <T0) so- 31 f 31) 26 (22) 24 0 3 ) 8 (7) 7(7) 60- 27 (25) 35 0 2 ) 35 0 3 ) 12 n i ; 15 f 14) 70- 23 f22) 20 M9; 17 M 5) 11 (TO; 13 <T1) SO- 4 (5) 4 (i) 4(4) 5<4) 3 0) All M ean SD 108 r lo i > 58.7 13 9 108 (07) 59.1 13 3 107 0 8 ; 59.1 12.5 N o. of cju eitio r.n jires com pleted sho-An in p aren th eses f ). 57 f51) 55.8 19 3 57 (53) 57.4 17 3 Primary lung cancer 10) 3(2) 1 4 (13) 8 (7) 12 (7) 15 ( 15) 3 (2) 56 (47) 58.8 15.5 1 No. 4 * Derir.itt number of i ing wood difference to cerneni ber were were in i to asbesto in 19 mer 2 control An anah Table 7, ' appeared tact with (9:1:1) ra seemed u bestos. T1 in the n copper: 1. T able M ales Expos! 1 1 i ! Male: 1 P < 0.001 F em ale Expost 1 I 1 I * One ch' Vol. V, Total F 1 1 4 6 9 8 12 II 5 57 165 ; in tlie second- lefinite or problisted in Table i textile manuake linings, or for most of the Mine or mill an to the differhardware storeas-cement prod- exposure and efinite or prob iO sears: 4 men on the job for s of IS, 26, 26, No. 4 M alignant M lsothliial 7 lmoks M r D onald el al. Table 4. sbcstOS Cement Copper Fiber elass Nickel Rubber Wood Occupational Kx;*o- :rc of M en to Certain Material* M ev /' heKil tu *77or* Secondary lun^ canter Primary June c a rter {100 men ) 2<i 17 f4) 6 (2) 6 (5) 5 12) 3 (1) 18 f l ) (96 men; 3 9 f0; 1 (0) 0 0 0 19 (0) 97 m enj 4 8 (0; 1 (0) 0 0 0 16 (0) Total exposures recorded 75 f 13; 32 (0) 29 ((), * Definite or probable exposure to the substances named in dust or vapor form in men aged number of men who were also defi nitely or probably exposed to asbestos is z' ven in parentheses. 9J7 ing wood, for which there seas 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 anahsis of these exposures is shown in Table 7, where it may be seen that the excess appeared to be in occupations insolving con tact with copper, nickel, fiber glass, or rubber (9:1:1) rather than with cement only, and seemed unrelated to possible exposure to as bestos. 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 main tenance work, wood-caulking ('ship). Residential histories indicated that 45% of male cases and 3S% of female cases had spent their childhood entirely in a rural area com pared with 40% of males and 3S% of females with secondary lung cancer, but the primary lung cancers were less often reared in rural areas (males 31%, females 28%). Xo differ ence was found between cases and both con trol groups after the age of 15 sears. 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, onlv 3 men and 2 women had os also deserve veral men had 1them. Exclud- 1 I I Primary lung cancer 71) 5 (2) 14 (15) S (7) 12 (71 15 (151 t 5$. S 15 5 T a b le 5. Distribution of Cases and Controls According to Their Occupational Exposure to Asbestos Males: Mesothelial tumors Secondary lung cancer Priman.- lung cancer Exposure to asbestos Definite Probable Possible Unlikely No. "1 9J 20 60 % 20 0 20.0 60.0 No. % j 3.1 2J 22 2 2 .9 71 7 4 .0 1No. % 4,1 16 16.5 77 79.4 All* 100 100 0 96 100.0 97 100.0 Males: Distribution of definite and probable groups compared with possible and unlikely: v = 21.5, 2 d-f., P < 0.001 F em ales Mesothelial tumors Secondary lune cancer Primary lung cancer Exposure to asbestos Definite P ro X ib le Possible U n lik ely Xo. % 1 2.0 -- -- 49 9S.0 Xo. % -- -- 1 1.9 51 Q S.l No. % -- -- -- 46 100.0 All* 50 100.0 52 100 0 * One child in each group dying under the age ot IS has been excluded. 46 100 0 m m m m v ipmpipu^ iwwiiim(uj,!w.pi.4-,.wipljwp.i mmm t i l ll~ f i)l^ C ancer October 1970 No. 4 Tari e 6. D istribution of Occupation? Classified Cnder D efinite or Probable K \;v>un' to Asbestos > M eseth e'ial Secondare Primarv tumors June cancer lunc cancer Asbestos mine or mill Asbestos textile manufacture Brakeiininc installation Insulation Other occupations involving contact with insulation materials Hardware store (handling asbestos sheet and pipe) Filled cas masks with asbestos textile 3 4* >5 5 i i i 0 0 0 2 0 0 i 0 0 0 3 0 0 Cigarette? per day _ Nil 10 or less 11-29 SO or more T otal* * Excluding Total 21 * Includes one person who worked in brakelining manuiacture. 3 4 ever lived within 20 miles of an asbestos mine. One of die 5 was a case. 3 had second ary lung cancer, and one had primary lung cancer. The possibilitv of contact as a residt of some other member of the familv bringing home dustv clothes from occupations involv ing the use of asbestos was also examined. Ex cluding 7 persons (5 cases and one in each control group') who were occupationally ex posed themselves (definitely or probably), there was one case in a female with definitehome exposure and one male with probable home exposure. In addition to 5 persons (one case and 4 with primary lung cancer) who were possible occupationally exposed to as bestos themsehes, 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 possible exposed at work to asbestos brought home dustv clothes. Thus, excluding tho?e persons with definite or probable occu pational exposure, there were 15 persons with mesothelial tumors. 8 with secondare lung cancer, and 10 with primarv lung cancer, who had had at least possible home exposure to asbestos dust. The frequence of cancer reported in close relatives did not differ from that in tire con trol groups. An anahsis of cigarette smoking habits is shown in Table 3. In both males and females, persons in the primary lung cancer group had smoked considerably more than those in either the case or secondarylung 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. D iscussion Though our study is not directly compa rable with those of Elmes et al.1in Belfast, and Newhouse and Thompson2 in London, it seems fairlv 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 na tional sample of cases derived from all parts of a verv i. rge countrv, whereas theirs were xrom 2 specific industrial areas, one a ship building citv and the other from a hospital close to a large asbestos factory. A second possibility cases which third point sure that 1 were collec of the groi was not s o : possible ii Thompson not compa: gation was selected fo1 on a popul. It was n bestos in tl Several stu exposure i risk of this our series < to match and geogr considered less, it was worth not asbestos w. lung canct in the can cancers w: The fin dicate tha T aele 7. Occupation a! Exposure to Certain M aterials of M en w ithout Derr.i *e or Probable Exposure to A sbestos Mevcthefial Seeordarv Primary t r-.ors lunz cancer lu n j cancer Cement onlv Cor,:ver, nickel, rubber. or f.ber glaas 10 fS) 9* <2) 9 <C> \ <T) 8 (2) 1 h>) 19 (7) 10 (7) 9 f2) * Irclu d in s three men aI=o exposed to cem ent. The number of men p o sn l y exposed to abe=tos is giver, in parentheses. 1. Elmes, O. L.: Di asbesto?. Br 2. Nev.ho liorna of pU asbestos in 22:261-20? 3. Selikofi < ` WmwHimui..' Jj. ii I I'JPMI f 1' W1j ,[,i tub i > | n * '^m|.m p.1ir*" Vol. ir, >rted in dose t in the con ette smoking i both males irimary lung lerablv more or secondary ? groups had of smoking or probable s showed no :s from cases ctlv compaBelfast, and London, it ice between os exposure teirs. There is for this, ed on a na m all parts theirs were me a shipa hospital A second M a l ig n a v i M usotu li jal T i. moks * M<Donald et al. 919 T a lle 8. A verage ILu! y Nurr.ber of Cigarette-, Smoked M ale Fem ale C.'i ' re tte s M esothe'N l Secor/ y t jrr.orb c;i e;T Me^theia tjrn o r- with Prim ary cancer expo- J re Mfc-othe!ial u rrib f' Secondary ]jn? caacer Prim ary 1,n.r cancer N il *0 or ie-s 11-29 3{) or m ore ?1 77 i7 n 40 41 19 20 19 20 21 22 37 39 18 19 44 10 11 47 50 54 36 2 10 4 20 13 65 15 29 52 9n 10 20 24 36 71 5 10 1 14 36 21 47 9 20 12 2, 1/ 1 nO Cm Total* 97 IV) IV) 95 IV) 20 100 50 IV) 51 100 45 IV) ` E xclu d in g 6 persons under 15 years o f age and 6 men and 2 women whose sm oking history was ryj\ recorded issibilitv is that o u r series was d ilu t e d b\ cases which they would not base 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 tire group to which thev 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.123 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.45Since our series, of primarv lung cancer seas selected to match the mesothelial cases in age. sex, and geographical distribution, it cannot be considered representative in itself. Neverthe less. it was probablv sufficiently so for it to be worth noting that the history of exposure to asbestos was vers similar to that for secondary lung cancer. Anv 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 mesothelial tu- mors are rare in C a n a d a . a n d it is somewhat doubtful whether there has been a true in crease in incidence since 1939. 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 anv 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 mesothelial 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 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 stud ies, 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 necessarv. 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 tire control groups. The interpreta tion of this finding is doubtful. REFERENCES 1. Elm es. P . C.. M cCauehev. W. T . E.. and Wade. O. La Diffuse mesothelioma of the pleura and asbestos. Br i t . -Med. J. 1:550-555, 1965. 2. N ew house, M. L., and Thom pson. H : Mesothe liom a of pleura and peritoneum following exposure to asbestos in the London area. Brit. J. Industr. Med. 22:261-269 1965. 5. Selikoff. I. J.. Churg, J,, and H am m ond. E C.: Relation between exposure to asbestos and mesotheli oma. .Yen* F ig . J. -Med. 272:560-565, 1965. 4. Selikoff. I. J.. Hammond, E. C.. and Chursr. J.: Asbestos exposure, smoking and neoplasia. JAMA 204:106-112. 1P6S. 5. Wagner, J C,, Slesgs. C. A., and Marchand. Pa Diffuse pleural mesothelioma and asbestos exposure in the north western Cape Province. B n !. J. fedt-sir. .Med. 17:260-271. 1960.