Document yrXqBX3mZXor0zxNkeEnaQ456

FILE NAME: Z< DATE: DOC#: Z< DOCUMENT DESCRIPTION :ZZZZW DDZZdZ --..,...... 3 EXHIBIT NO. IS EMIOLOGY OF PRIMARY MALIGNANT MESOTHELIAL TUMORS IN CANADA" A, D. McDoNALD, A. HARPER, 0, A. EL ArrAR, AND J. C. McDoNALD ~, sex, date and diagnostic jClJU4UUl1 obtain quality. j illness sh lung cancel taia reasonably"". advantage that se All fatal malignant mesothelial tumors known to pathologists in Canada be were included, but ""0 tween 1959 and mid-1968 "'ere registered. They numbered 165 (1 per million population per annum): thirds were in males. Occupational and residen tial histories were obtained "blind" from relatives and friends of 90% of the cases and 2 matched control series. An association with definite or probable occupational exposure to asbestos was clearly demonstrated, but only 20% of male cases and one female case had any such contact. Almost ~11 the excess was in the manufacture and industrial application oE asbestos rather than in mining or milling. No association was found with lesser degrees oE occupa tional .exposure or residence in asbestosmining 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. second main q ues mesothelial tumor smoking in the san cu, and, for this 1 cases of this disease ..A field survey , testigators (docto and public health Itlatiws and frien pleted a detailed ( French relating te direct household e tory, and smokin Was given to the , EVlDE:\CE FOR AN ASSOCIATIO:\ BEnVEEN )[A- . lignant mesothelioma and asbestos exposure rests mainly on the remarkable concentration of cases reported by ,\\'agner et al,5 in the crocidolite mining areas of So1.1(h Africa, the casecontrol studies of Elmes et al.i in Belfast. and ::\ewhouse and Thompson2 in London. and the considerable excess mortality due to this disease observed by Selikoff et al.3 in American insulation workers. The survey described here was undertaken to obtain a more ?enerally representative view of the problem m one of the 2 major chrysotile-producing countries of the world. Our aim has been to study all fatal cases known to have occurred in Canada since 1959. of Pathologists or the Quebec Association of Laboratory Physicians inquiring whether I hc\ had seen, any fatal cases of primary mali~Il:tIl'1 tumors of the pleura or peritoneum diagll,,~('d by autopsy or biopsy since 1959. In due (I '11 ,(' we obtained a reply from them all, and. I' hi, was in the affirmative, a personal visi: .\ :,\ made by one of us to review the record~ .1\1(1 to exclude cases which did not meet tlil'~C criteria or about which the pathologist had serious doubt. In all, 165 cases were found: 113 were pleur;tl, 45 peritoneal, 3 pleural :l1ld peritoneal. and 4 pericardial. The diagno~i, was supported by autopsy in two thirds of the cases and by biopsy in the remainder. L:lter. we plan to have material from as mall\' as ~ possible, all err panies were listed of the exact natt' relative was then yolved contact w ttment. copper, n a check list was t: .~bject had e\'~r 1 , following: locomc ing, overhauling, large boilers or st mestic heating' e< .proofing, fireproc .~ prefabricat( .~ buildings; rn or dutch plates; possible reviewed by a panel of patho!ogi~t METHOD During the visit to the pathologist, 2 i 'Ial control cases-one primary and one sec<llId At the end of 1967 we wrote to the 423 ary lung cancer-were selected from the all' . , members of either the Canadian Association topsy or biopsy records, matched for sex and. as closely as possible, for age and date of From the Department of Epidemiology and Health. death. In 2 instances, no adequately match, McGill University. Montreal. Canada. . I A preliminary report on these results was pre ing case of primary lung cancer could be sented at the International Conference on Pneumo found. Two control series were chosen in or, t coSniuopspisoratet dJobhyananegsrbaunrtg frionmAtphreil, In1s9t6i9r.ute of Occu- der .to examine 2 types of question. Primarily. pational and Environmental Health of the Quebec we wished to know whether persons who had Asbestos :\lining Association. . died from malignant mesothelial tumors had Il!: . This survey was made possible by the great help given us by pathologists and members of provincial and differed in their past exposure to asbesto~ -nc! other health departments throughout Canada. \\'e are certain other materials from comparable ,cr f; also much indebted to all those who did the field sons in the general population. Comparabil. work and to the friends and relatives of the deceased for their cooperation, ity demanded that the control series shollhl :q Received for publication April 9. 19;0. comprise persons matched with the cases for 1960 1961 1962 1963 1964 1965 1966 1967 1968 ( Incidenc 19~ ciation of :the: :l!t\ naI:Z:;'l1t lia.:;",."'. cl tiel' -,' .ld, :: , i,,;: e, ,.' ,;:' Jgh.t . __ " e fc:..:n-=!: :tlr:l! :tlLl c1iaznosis -ds of the ~r. LJt-:r. m:!,-', "s 'o~i,> t, 2 :' ~ sec, I th-::- ::.1sex :md. date of y m3tch :ould be ~n in or'rim3.rih, who h:ld nors ?' ~d ~5to-; : ,..1 :lble [1p:!r:: 1s sh:.:,!,j ~o, 4 ~f.\l ,:'\,\:'\T MFSOIHFII.\I. Tt'Mol{, 915 1ge, ,<:X, (};I(<: a Ill! pl.lt<: of ll<:ath, ane! post mortem diagnostic procedure. To insure that ,information obtained from relatives would be ~~qUal quality, it was important that the :-. inal illness should also be similar_ Sec.t;ndary lung cancer seemed to meet these criteria reasonably well and had the additional advantage that se,'eral primary cancer sites were included, but none were in the lung. A second main question was whether primary mesothelial tumors were related to tobacco smoking in the same way as primary lung cancer, and, for this reason, a matched series of cases of this disease was also selected. A field sun'ey was ananged in which in\'estigators (doctors, public health nurses, and public health inspectors) sought out the relati"es and friends of the deceased and completed a detailed questionnaire in English or French relating to occupation, residence, indirect household exposure to dust, family his- , tory, and smoking habits. Special emphasis aw.~aspogsisviebnle,toaltlheemopclcouypearstioonralemhipsltooyrvin. gSocofmarpanies "ere 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. Fina]ly, a check list ",as used, to inquire whether the subjec~ had eYer been employed in any of the followlllg: locomotive repair shop; shipbuilding, overhauling, or breaking; installation of large boilers or steam pipes; insulation of do. mestic heating equipment; building-soundproofing, fireproofing, heat retention, assembling prefabricated buildings, and demolishing buildings; manufacture of brake linings or clutch plates; mining industry; textile in- dllstr~; L<:lllt'll t ilhhl>tr~; dllt l.. ur tI :tIlSP0rt industry. No inter'\'iewer 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 (91 %) of the 493 cases and controls. FI~"l>INCS The distribution of cases by province and year of death is shown in Table 1, and by age, sex, and site in Table 2. ~~ore cases were found in 1966 and 1967 than ill 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 a 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 incidence 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 accounting for much of the difference. Three quarters 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 ~ control series were very similar in age distribution and in the proportion of each for ,,'hich 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 materials in dust or npor form. Whereas all 3 TABLE 1. Year 1960 1961 1962 1963 1964 1965 1966 1967 1968 (1st half) Incidence/million/year 1960-1967 Distribution of Cases by Year of Death and Province Ontario Quebec Other PrO\-ince5 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 46 70 49 165 0.8 1.5 0.9 1.0 fl I )i:::ll ;-,1 -l ~d ;J~r;:o-;- f'~. '-I 'I 1(, 1;' l\ (;{)< j ll',- '~ ;- l ' , ,;,- , I i Iw , ;1 : : n :1" "'"\' ('", l' - ~l t ()' c; ,: : '(" , , : 'I ",>" ! I 11' J1 " 'c ',' ']', ",I IT ;] ('f- 'I( " n' 1''] ,' ,,,' ,I 'C)"( '1'\ ." (', 1:1 ( 1';);1 '0[1 .,,,' : CC' (;1' 1('\ 1; I" ! : ') ;: I' (~ ) flf) (~O 31 .c'. ) , \ . !lli' TABLE 4. Occup,nional Exposure of ~I~n to Cert.lin ~I.ltcri.lls Mesothelial tumors Secondary lung cancer Primary lung cancer Asbestos Cement Copper Fiber glass ~ickel Rubber \\"ood (100 men) 20 11 (4) 6 (2) 6 (3) 5 (2) 3 (1) 18 (1) (96 men) 3 !) (0) 1 (0) 0 0 0 19 (0) (97 men) 4: 8 (0) 1 (0) 0 0 0 16 (0) Total exposures reccrded 75 (13) 31 (0) 29 (0) Definite or probable exposure to the substances named in dust or vapor Corm in men aged 18 or more. The IIIIDber of men who were also definitely or probably exposed to asbestos is given in parentheses. or pr. ,fJ' 1 T:ll.:-: . m:lll:; in~'. fl! .t of ,: ~ or n1i:: e c!i;;. r .. re ,I. It: I~ : -l Illt;~ job for 26. 2';. fug wood, for which there was evidently no difference between the 3 groups, 37 exposures to cement, copper, fiber. glass, nickel, or rubber were recorded for the cases, of which 12 ,.-ere 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 (9:1:1) 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; fib er glass: municipal main tenance work, wood-caulking (ship). Residential histories indicated that 45% of male cases and 38% of female c<ctses 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%). Ko difference was found between cases and both con trol groups after the age of 15 years. Excluding 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 de:.erw: len Ind Exchd :ml:'y cancer (2) (13) (i: (i, (15 (2 ; (~; 1 .8 .5 TABLE 5. Distribution of Cases and Controls According to Their Occupational Exposure to Asbestos ~Iales :'vIesothelial tumors Secondary lung cancer Primary lung cancer Exposure to asbestos Definite Probable -" . Possible Unlikely ~o. % IJ 20.0 20 20.0 60 60.0 Xo. % :r 3.1 22 21.9 71 74.0 I} LI Xo. % 3) 16 16.5 77 79.-t :\11- 100 100.0 96 100.0 97 100.0 ';>-p Males: Distribution of definite and probable groups compared with poss-ible and unlikely: Xl = 21.5,2 dJ., ';'. < 0.001 Females Mesothelial tumors Secondary lung cancer Primary lung cancer Exposure to asbestos Definite Probable Possible Unlikely No. % 2.0 49 98.0 No. % 1.9 51 98.1 No. % 46 100.0 All' 50 100.0 52 100.0 46 100.0 One child in each group dying under the age of 18 has been excluded. I' 't ~I' ",:i! -: l - i I ~: ' i ( ~ t" I ~ :I ~ . i - ~f f ? JI I .\ IILF (), I li,( rib,,( i"" 1( kn,I'" (i ..", ( I.,--i lied I 'lII"'r I ldi 11; (l' or "r..Io.c1 .Il E)\.I'''~llrl (0 . \~l>l'~to~ ;\Iesothelial tumors Asbestos mine or mill 3 Asbestos textile manufacture 4- Brnkelining in"taUation 2 Jnsulation 5 Other occupation;. involving contact with in5ulation material,; 5 Hardware store (handling asbe~t()s sheet and pipe) Filled gas masks wi th asbestos textile Secondarv lung cancer 1 0 0 0 2 0 0 Primar)' lung cancer 1 0 0 0 3 0 0 TOTAl. 21 3 -l * Iricludes one person who worked in brakelining manufacture. 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. Excluding 7 persons (5 cases and one in each control group) who were occupationally exposed themseh'es (definitely or probably), there was one case in a female with definite home exposure and one male with probable home exposure. In addition to ~ persons (one case and 4 with primary lung cancer) who were possibly occupationally exposed to asbestos themseh'es, 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 d, ,e relatives did not differ from that in the, l' trol groups. An analysis of cigarette smoi- ~ habits is shown in Table 8. In both m.1:c" and females, persons in the primary hlllg cancer group had smoked considerably more than those in either the case or secondan lung cancer groups. The latter 2 groups ha~1 almost an identical distribution of smoking habits. The 20 men with definite or prob:1hll' occupational exposure to asbestos showed 110 great difference in smoking habits from Cl'" without occupational exposure. DISCUSSION Though our study is not directly corn P:1rable with those of Elmes et a1.1 in Belfast, and Xewhouse 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 l' 'ttional sample of cases derived from all p:. " of a very large country, whereas theirs ,,". l:' from 2 specific industrial areas, one a sh i pbuilding city and the other from a hospital close to a large asbestos factory. A secont! TABLE 7. Occupational Exposure to Certain l\Iaterials of Men without Definite or Probable Exposure to Asbestos Mesothelial Secondary Primary tumors lung cancer lung cancer Cement only Copper. nickel, rubber, or fiber glass 10 (5) 9* (1) 9 (6) I (I) 8 (2) 1 (0) 19 (7) 10 (7) * Including three men alsl) exp'lsed to cement. The number of men pos,~jbly exposed to asbestos is given in parentheses, 9 (2) -_.~o. '. 10 or less 11-29 30 or 1\10' .,TOTAL* Excludill possibility cases whirl third poin: sure that were coUe( of the gro was not so possible i: Thompson not compa gation wa~ selected 0 ona popul It was n bestos in t: Several Stll exposure I risk of this our series i to match and geogr considered less, it was worth noti asbestos w~ .._lung canc( in the cau~ -: cancers wa ',.", The fine . 'dicate that ..... : 1. Elmes, "0. L.: Difi ", asbestos. Bri 2. NewhotJ noma of pIeubestos in 22:261-269, l 5. Sclikolf. T,, \ h l 1(;:--'.\ ,\;1 :\ 11:: ,< 1I Ill I 1 \ I ... \IO~' .\1, /lu'ltlltll'I (//. !11 V Ir- . I~'-;':; Cigarettes . per day Xii 10 or less 11-29 30 or more TABLE 8. :hcr.tge Daily :'I:umber of Cigarelte" Smoked Male Mesothelial tumors 21 22 17 18 40 -11 19 20 Secondary lung cancer 19 20 11 Z2 37 31J 18 19 Primary lung cancer 4' -I 10 lJ 47 50 34 36 Mesothelial tumors with asbestos exposure 2 10 4 20 U 6j 1 5 Mesothelial tumors 19 58 Q 18 to 20 1 -I Female Secondary lung cancer 36 71 5 JO i J.J. 3 6 Primary lung cancer 11 -17 9 20 11 27 .~ 7 TOTAL- 97 100 95 100 95 100 20 100 SO 100 SI 100 45 100 - Excluding 6 persons under IS year:." oi age and 6 men and 2 women whose smoking history was not recorded [ in cl, > the COi.smokillg .th males ar)' lung bl}' more ,econdar) ::lUpS h;1(1 smokini-, probahle lO\\'ed 1'" 'om ca- . " compalfast, and ndon, it between exposure 'S. Thel': for th: on an all pall~irs wert: ! a shiphospital \ se'cond possibility is that our series was diluted by cases which they would not ha\'e accepted. A third point is that we took great care to insure that the histories of case and control were collected and coded without knowle.dge of the group to which they belonged. This was not so stated in the Belfast SUH'e\, and not possible in the study of Newhouse and Thompson. The findings of Selikoff et a1.3 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 asbestos 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 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. Xeverthe.. less, it was probably sufficiently 50 for it to be worth noting that the history of exposure to asbestos was very similar to that fo,! 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 increase 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 ha~ any such exposure. No difference was found between cases and the 2 control groups regarding lesser degrees of occupational exposure or residence in asbestos-mining areas, but, in 10% of the mesothelial tumors compared 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 industrial 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. ~ine men with mesothelial tumors had worked in occupations unrelated to asbestos but involving contact with copper, nickel, rubber, or liber glass compared with one in each of the control groups. The interpretation of this finding is doubtful. REFERENCES l. Elmes. P. C., McCaughey. W. T. E.. and Wade, O. L.: Diffuse mesothelioma of the pleura and asbestos. Brit. Med. J. 1:550-555. 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. 22:261-269, 1965. 5. Sel!koff, I. J.. Churg. J.. and Hammond, E. C.: Relation between exposure to asbestos and mesothelioma. New Eng. ,. Med. 272:560-565,1965. 4. Selikolf, I. J., Hammond, E. C., and Churg. J.: Asbestos expo~ure, smoking and neoplasia. lAMA 204: 106-112, 1968. 5. Wagner, J. C. 5leggs, C. A., and Marchand, P.: Diffuse pleural merothelioma and asbestos exposure in the north western Cape Province. Brit. J. Industr. Mi'd. li:260-2il. 1960. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -----~--------- -~~-,...-..:~-~-. - - - -