Document rB2zmpxXaQ4J9pe6YYy3DL4g0

An kpideiniolo^ical Study of Lunic: Cancer in Asbestos Miners DANIEL C. BRAUN, M.D., and T. DAVID TRUAN, M.A., Pimburgh K\*T 'IllCc tile prollolll levd llliTc.-l'e- Ml .he incidence- <*f lung cainar among males became apparent, there I;i\_ been attempts In a'*ii;i.Lti- il \vitli mu- <>r another of thevariou- dements in tin- environment of man. Tile approach Used ly some workers has beut to siispi cl one or several sub-tanees anil tlieit >el aliottt in an intensive 'e-arch for lung cancer among jn-r-on.- who have hail anv cxpo'iire- to thoe materials. In thi- connection. Smith'- write.': "file tendency of authors reporting the coinciilental occurrence of primary him; cancer with >ilieosis or with any other theoretical ctiologic conditions, has liven to eniiilu-i/.e the percentage relation'll:; in extremely 'inall series ot cases, with control e.i'C' which are not in any way comparable. It would seem inevitable that asbestu' should come tinder scrutiny in this manner, becati'c prolonged exposure to this material is known to cause a specific type of pneu moconiosis, .and because persons who 'how thi' form of pncumoconiosi' often come to autop'V and provide a readv source ot m.alerui for study. It w;t' in thi' wav that report' of the simultaneous occurrence ot him; c.mcer and adiesto'is began to accu mulate after the report of a c.i'i- he Lynch and Lilith1-'' m 193?. Within the next in tears, about 1? additional ea'C' were re ported. and in 19?4 Men wether 70 rev iewed all death' from a'bestosi' recorded in Lngland since March. 1924. I.unt; cancer oc curred in Li'i of these eases. (doyne.'1' Acn`|>lt'i for puMiranon tan. 20. 10?.' 'i 'his study u.o made ]>. is 'if dv throne!: a vmntn frn: the Quebec Asbestos Minnie A--viaiinti Medical Direen-r 'Dr. P.rann) and S: itistiral Vi.a-nltant (Mr TniaiA. I in lu> rial lbcicne 'iindatii hi i whose woik i' al'o luouenllv referred hi as establishing a connection In-tween a'bc' tosi' and cancer of the mm;. reported in 1**51 that cancel ot the lum; was present in 14.1rr of a-liestosi' c.i-e- examined hv him. In 1941. Xonlmamt and Surge ' claimed to have produced lung cancer n: mice which they exposed a-bestos do-: Since I9.il. addon II.li '>1 `."MIUT ti! the lung coexisting with ,ibv-tosis have been reportetl. and. according 'o I lucper about 1IM) such ..t'C' had liven repoiteil Up to lu.'5. As a result, an .i"oeialion l>etwicn the two disease' appeal' to have been ac cepted by many author', and 'ever,.! writer' were using the term i'be',o'i' cancer' oi the Inns;. Werlier."' in P'sJ. -;nte-d eate- goricallv that m ~'r to !7'i of eases asbe'tosi-. after a latent period of about !'j to 29 veai'. carcinoma he-iomcs e-stab li-lie'll in the- lung On the other hand, not all author' m eepted thi' alleged ,i"ociation without reservation. Nmpc m I'kVi reported that lie had discovered im ca-c' ol lung cancer among 620 c.i'i' of nsbe'to'is which lie had examined: and m l`42. 1 [olleb and Aiigrist *' expre"i-d the opinion that the number of ivi'i-s of .I'bi'tosi- with lung cancer was too small f,,r statistical evalua tion. In 1947. M'egcluis" re[>orted 12<) radiologieallv diagnosed eases of asbestosis among 47o worker' in Finkind, and found no eases of lung cancer in this group, (loldblatt and (ioldhlult in their section of Merewethcr's latest book.'14 state: "Hut at no stage in all these imprc"ive researches was any clue obtained which might have offered anv support iu the possibility that asbestos could act as a carcinogen. I ht-ri 62-4 HER 0004228 r. t. ii iUNG CANCER IN ASBESTOS MINERS t no reliable criterion by which one can nticipate carcinogenicity and, as is well nown, relatively minute changes in the tructure of a chemical carcinogen are suffiient to diminish or eliminate carcinogenic ction. If asbestos i> indeed to be regarded as a arcinogen, the need is felt to demonstrate ome property which can be regarded as omething more than inertness." These authors advance the theory that, ntil some more experimental evidence of irect carcinogenesis by asbestos or a deomposition product of it can be obtained, sbestos might be considered as a "co-carinogen" which only induces a further deelopment of a preneoplastic condition rought about by something independent of he asbestos, such :i' an endogenous factor. Thus the literature, while tending to supon the thesis that n?bcstosis is in some ray related to the development of lung ancer. is by no means unanimous. Altocthcr, it is perhaps more confusing than nlightening. A careful review shows that he majority of the reports are clinical and tot epidemiological. They lack many elenent' necessary for the application of pidemiological techniques to their content, ,:k1 most of the authors do not make claim 0 having done so. What has happened is hat succeeding authors have drawn concluion.s and generalized beyond the scope of he work? which they quote. Nowhere, for xample, have we found references to a 'ofiliation of aslx*>to> workers, although everal authors who have quoted the oberved incidence of lung cancer m autopsies fersons zoho also had ashrsto.sis imply hat this incidence applies to asbestos work' s, generally. We have likewise been 1 lable to find any study which actuallv nlculated the incidence of lung cancer ;:nong a population of persons who had isbestosis, and not iust those who came to tutopsy. W ith the exception of a paper iv DolI,2s none of those reviewed gave anv lata on exposure and dust concentrations, tnd even Doll's paper merely mentions \raun--Truan I "scheduled" areas, by which is meant, "those areas where processes are carried on which were scheduled under the Asbestos Industry Regulations of 1931 as being dust}'." There is, furthermore, a complete kick of definition of terms as used in the pub lished literature. For example, the term "asbestosis," as used, may refer to changes observable only by microscopic examination of the lung tissue, or it may mean a radiologicallv detectable condition. Most of the published rejiorts obviously included women among their cases, but some of them do not give the number or profiortion of women involved in the study. There is also a lack of uniformity as to what type of exposure most studies have dealt with. Of 99 cases enumerated by Hucpt-r58 in 1955. only 10 appear to have originated in the I'nited States, and 7 in Canada. Some of the earlier reports ap parently included asbestos miners, but it can be assumed, since 82 of the 99 cases had originated in Kngland, and since no asbestos mining operations are carried on in that country, that most of the reported cases have involved workers in the textile or fabricating industries. Such factors as smoking habits, family history of cancer, length of time in the industry, and age of the individual case arc also notably absent in the majority of these reports. With this understanding of the limita tions of the existing literature with respect to epidemiological generalization, it may be of value to consider in somewhat more de tail some representative earlier publications, a few of which were referred to briefly above. f ()ne of the most detailed studies and one which deserves the most serious considera tion is that rejiorted by Doll28 in 1955. This study reviews causes of death among asbestos workers based on coroners' rec ords. It also attempts to estimate the risk by studying records of men who worked for at least 20 years in exposed situations. 635 HER 0004229 JiiWTTi A. M. A. ARCHHES (>! tXIHSTRIAL HEALTH Doll concluded that lung cancer was a spe cific industrial hazard of certain asbestos workers and that, after 20 years of expo sure, the risk is 10 times as great as for the general population. This article is important for several rea sons, in addition to the definite conclusions at which it arrives. For example, it begins by stating that "in view of the infrequency of asbestosis. this large number of cases (61 cases of lung cancer) suggests--but does not prove- -that lung cancer is an occupational hazard of asbestos workers." Neither this article nor any previous one which we have examined presents any fig ures to prove that asbestosis is an infre quent occurrence. Estimates of the number of persons potentially exposed to asbestos dust in the United States alone van- from 10,000 to 35,000. and the incidence of as bestosis of any degree might be higher than Doll imagines. This study, like so many others, involves autopsy records. The number of persons involved in the statistical analysis is only 113, representing only 1.042.25 man-years of life. It is also true that in selecting men who had been employed for at least 20 years, the study automatically excluded those who died from other causes after shorter employment. Another reason why this publication is of importance is a statement which it con tains to the effect that "the strongest evi dence that it (lung cancer) may be a hazard (in asbestos workers) has been produced bv Merewether and by Gloyne." In 1951 Gloyne41 presented a review of 1205 autopsies on persons who had worked in various dusty occupations. This number included 132 asbestos workers, of whom 121 showed "pneumoconiosis"--pre sumably asbestosis. Primary cancer of the lung occurred 17 times in this group, an incidence rate of 14.19c for lung cancer among asbestosis cases coming to autopsx. There were in his series 796 cases with sili cosis, and 6.99c of these also showed pri mary cancer of the lung. The incidence of lung cancer in other forms of pneumoconio sis was 6."9c. and in 169 cases which proved not to have any type of pneumo coniosis it was 8.39c. Gloyne considered "the mortality of the aslx*stos workers" to be "disturbing." First of all. it is obvious that the paper docs not deal with the "mor tality of asbestos workers." and secondly, it must be borne in mind that all of Dr. Gloyne's case.- were submitted to him for study because the findings were unusual for uncomplicated pneumoconiosis. It can reasonably be assumed that cases, including those of asbestosis. m which the findings were not considered unusual were not sent to Dr. Gloyne for examination. As a mat ter of fact, in the same paragraph in which he expresses concern over the incidence rate in asbestosis, Dr. Gloyne himself! points out that the rate for lung cancer! based on necropsies at the London Chesti Hospital was 21.3G while the figures off the Registrar-General showed only 2.49c., He thus recognized that autopsies on a cer tain selected group of cases were not rep resentative of the general population. It would seem, then, that notwithstanding the value of Dr. Gloyne's work, its importance as an index of the prevalence of lung can cer in asbestotics has been misinterpreted by some who have quoted him. All that if really shows is the fact that in a group of 121 cases, selected for special study pri marily because they seemed abnormal by preliminary examination, 17, or 14.19c, had lung cancer. Merewether in 1947. in the report of the Chief Inspector of Factories, reviewed all cases reported between 1924 and 1946 in which asbestosis was the cause of death or a coexisting condition. This work was later extended to include all such cases re ported up to December, 1954. by which time there were 344 deaths, including 205 male) and 139 females. Among them were 55 cases (169e) of cancer of the lung, 41 in males and 14 in females. It is quite possible that a large number of asbestotics who did not die of their asbestosis, or in whose 636 I'i>l. I', Junr. 165/ HER 0004230 I.USC CAXC l-.H IX .1 V/t/v T< is MIXERS death certificate it was not mentioned, may have been missed.- The import of this 169r is enhanced In die simultaneous statement that the incidence of lung cancer in autop sies of the general population is only l^c. 1'he danger of attempting to compare a iate found in .544 ca-'-s with the rate for die general population without respect to age. occupation, and mail}' other variables, such as smoking h.dnls, is obvious. Lynch.7,1 who with Smith had reported the first case in ]'<.55. reported 4 cases of carcinoma of the lung in a series of 49 autopsies on workers m an asbestos manu facturing plant who were shown to have "demonstrable deposits of asbestos in the lungs." This, i,; four-e. is not necessanlv identical with the it-ease asbestosis. Lynch, himself, point' out that, although this is an incidence of S 2'r . "both figures are ton small for very serious statistical types of .'.alculaiion." Nevertheless, later writers have used tin- panel- to strengthen the case for an association of carcinoma of the lung .vith asbestos^. !; is aLo of nucrest that Motz l'3 found onlv the same number of .'ases nt lung' cancer in a series nearlv 10 lines as large, i . 4 in 478 cases of isbestosis. Behrens, as cited by Mercvvether.7" esti- nated tliat. ot dn1) ,w- of nsbe'tosb in the iteiature. 44 show! .'`.s.ociated cancer of he lung- giving an incidence of 14.2'r. I his i. an i Iki-: r .n of generalizing an ncidence oPt.tnud n a group of ca-es vhich. were mid. >vi!>lv> 11 v reported only aa.'c some i|i.'u .bowed lung cancer, to )oss|k;v hundred- asbe'fofics whose vises Were in or repom-d. The '.mie ap- ilies to the oiiriitsion of Telekv.'7' who ippears to hav. reviewed reports of 30 ultopsies on pe'soii' with asbestosis among chub fi cases oi lung .nicer occurred. In- orm.ition from -omve' such as thc'e does lot justify gwnei "liizations with regard to Mortality rads Perhaps no mu ini' written 'O extenively on tile subjeit .1' has T Lieper.'- '<l n 1955 lie review.1 the a. .IS Ss reported rjutt--Tr\um prior to that date and enumerated a total of 99. Eleven of these were those dis cussed by Doll5* and may have been cases covered by other authors. Light were dis covered by Kennaway and Kennavvay41 in an analysis of death certificates, and. unless Merewether's study was incomplete, these cases should have been included in his re port. Of the remaining 80, it is i|uite pos sible that the 31 contributed by Mercvvether and the 17 by < iloyne contain some duplica tion with each other or with those of other Knglish authors. Principles of the Epidemiological Method Dorn3" has pointed out that much of what is wav thought to be pertinent concerning the comparative frequency of lung cancer in different population groups has been de veloped from the analysis of clinical ma terial. particularly surgical and autopsy record', supplemented to s,iine extent by the reported impressions of various clini cians based upon their personal observa tions. More recently, however, attention has turned to the systematic investiga tion of this problem 'w the same methods that have proved -o successful previously in the study of communicable diseases, that is to s.iv. l.v epidemiological methods In order to apply this method of investi gation to ihe problem under discussion, we were of ihe opinion that a study should be planned -. as n, provide i 1 ) a well-defined population group: i2l available data for all memliers of this population, including the healthy as well as the ill: i.5i a sample which is truly representative of the popula tion: l4l reliable and valid observations relating to the piohlein of the study. A serious defect, eouimon to most of the studio which have been reported, is that little or no miormation concerning the healihv people in die group eenis to have U-en available to the author. In order to draw a generalization regarding' all asheslo. workers, ii i- necessary for a study to in clude hvujg per>'>!l' its well as the dead 637 HER 0004231 -I. il. A. A/iCHin-.s- oh IXIHsTKlAl. tit.At TH Limiting the investigation In cases coining ift- autopsy, as has been frequently done in earlier studies, 'till further restricts its use in generalization. The problem with which we are concerned i' whether asliestos miners exq>erieiice more lung cancer titan docs the general [>opulation. The answer necessitates the collection of reliable infor mation on asbestos miners us a group, as well as on the general population. It seems advisable to discii'S the differ ences Ixtweeu the epidemiological approach and that Used in the 'Judies which have liven reported t" date A \erv important consideration is the fact that lung cancer, in 'pile of its increasing numbers, i' still a disease of low incidence: that is. in a given [opulation not many persons will contract this particular disease. This fact requires that large samples or groups must U- stud ied to provide meaningful results. Recognizing the difficulty of obtaining such large samples, most earlier writers deviated from the epidemiological method and sought to circumvent the requirement of observing well persons by ill compar ing the relative frequency of cancer in cari ous sites: 121 comparing the relative frequence of cancer in a group of hospital ized pitieiits: ( 31 comparing (he relative i requeue! of cancer in a group of cases coming to autop-v. Attempting to compare two population groups, looking only at the relative fre quency of cancer in various IkkIv sites, may result in finding a higher percentage i relative frequency i in one of the groups, when, in fact, the mortality rate of cancer of a particular organ is exactly the same m both groups, 't'liis is \erv clearlv dem onstrated in the excellent article bv Dorn.30 The mortality rate from a particular cause is the true measure of comparison. It is apparent that selected groups such as hospitalized patients or autopsv eases may not be in any way representative of a larger group, and that in dealing with such samples, the observer mav easilv find more cases of a given disease than would be found m another group of the same size, but representative of the general [xipulation. It is true that investigation of cases from such a sample can furnish information valuable for research, but the use of this information in drawing generalizations is necessarily restricted. Jt is the obligation of both the investigator and of those who read his re]>ort o> make profier comparisons and to draw only those conclusions which are valid and justified. A g'xnl statistical study of cases of cancer "f the lung occur ring in a group of autopsies can lead to a proper inference concerning the frequency of lung cancer among case' coming to autopsy, hut only to such cases. For m formation from such a study to U- pro jected to some larger group, it is necessary that the autopsies represent a good -ample of that larger group. To assume that such is the case in any particular series is dan-| gerous and likely to be false. ; There is some danger that the figures; reported by some authors may be mi'Con i 'trued as applying to asbestos workers or> even asbestos miners, when, in fact, the! authors in question do not make this gen-, eralization, nor can the generalization be; made for the reasons stated. Close sludv of: the reports reveals that the percentages, cited relate only to die group of autopsies covered by the particular investigation. T he present study, in contrast to the earlier works, has been planned to utilize the epidemiological method. A well defined group of asbestos miners has been estab lished in 'tivh a way that it constitutes ;i good sample of the whole population of asbestos miners m Ouebcc. Data tor all members of this group have been collected and analyzed. Those concerning lung can cer have received most careful considera tion. Details of the methods emploved will be set torth later, but live type of approach is considered to permit of fair comparison; and valid generalizations. Collection and Analysis of Data A preliminary survey of potential source! of information in February, 1956, involve* fi.W l*ol 17. June HER 0004232 lUXG CAXCIiR IX ASBESTOS MIXERS discussions with the physicians in charge of the asbestos companies' programs and ivilh clinicians, pathologists, representatives Dt City and Provincial health departments ind of the Canadian Cancer Society, and Dther interested persons. It was found that morbidity data, although somewhat limited. |cere available from such sources as the hospitals in Montreal and Quebec City, and the 13 cancer detection centers in the Prov ince. However, became of the high morjalitv in lung cancer, it seemed advisable jo depend upon data relating to deaths. These we found to be obtainable at the lital statistics department of the Mini-try >f Health in Quebec City. Front the pre liminary survey. it was apparent that extenlive and detailed information could be fathered with respect to both the persons tmploved in the asbestos mining induslrv md the mortality figures for the general lopulation. Following thi- exploratory survey, the intial effort was directed to the collection tf data relating to all workers who had keen processed through the rlinic at Theljord Mines -nice it- inception in lfJ47. and similar information regarding all workers tt A-lvc-tos. Quc. Data from the clinical ccord- included the age. family and perbnal medical hi-toric-. smoking habits, lumber of years of exposure, nil estimate if weighted exposuir. and the course of he individual - hi-alth -i.atu- or the cause |f bis death. ! From this 'iiionnatiou il was possible a formulate a hort" which could be well efined. should be representative of the hole group, and could be followed for a efiiiitr period of lime. All of the available xperieitee indicaies ;li.it die development if asbeslosis hi less limn fi\c vears of ex- josure must be -omcvvhat rare Aeeordy, the cohort was defined as including (very miner who had a total exposure of jve or more years. and who was on the mployment rolls in 1950. Ofiiec and other onexposed personnel, regardless of length f employment, were not included. This niun--Trmin cohort was then followed by means of the annual physical examination records through a six-year interval, 1950 through 1955. All data regarding this group were then tabulated in order to determine the characteristics of the cohort. For those who survived the entire |>eriod, reference was made to the physical examination results and x-ray findings at the end of the period. Those who had died were tabulated sepa rately, and the cause of death was corroborated by examination of the death certificates. A further search was made concerning those in the original cohort who remained unaccounted for when the living and the known dead had been tabulated. They represent men who bad left employ ment through retirement or resignation. F.venUially, all but a small number of these were accounted for as either living or dead, and in the latter event, the cause of death was substantiated in a similar manner, and the results added to the original list of deaths. Death certificates for the Province of Quebec for the years 1952 to 1955, inclu sive, were reviewed in the department of vital statistics of the Provincial Health Ministry, together with statistical sum maries of the causes of deaths in the Prov ince by counties. All cases in which death was certified as having been due to pri mary cancer of the lung were examined for such information a> place of residence, occupation, date of death, hospital in which death occurred, and whether or not an autopsy was performed. I a>es in which lung cancer was given as ,t cause of death, hut in which it was uni specified as to whether the cancer originated in the lung, were also reviewed in an effort to include all instances of primary carcinoma of the lung in the studv. The staii-tics for the Province of Quebec relate to population, total deaths from all cause-, total deaths from cancer of all type-, and deaths from lung cancer. Thc-e were collected and tabulated by counties and bv -ex for the years 1950 to 1955. inclusive. hS't HER 0004233 A M A. ARCHH'HS Ol IXDLSTR1AL HEALTH From them, death rates fur the general population of Quebec and of individual counties were calculated for specific years and analyzed by cause. Practically all employees of one company are covered by a group policy of lift insur ance which, fortunately, nearly all of then: continue to carry when they retire. A very few are not covered by this policy, and those who leave the industry for one reason or another except retirement usually are no longer covered, but this is likewise a small number. As an additional check upon the information obtained from the clinical record* on this group, the records of the life insurance compiuiy were examined for all death claims paid under the policy, and particular notice was taken of the claims iu which the proof of death was based on cancer of the lung. Deaths from lung cancer among asbestos miners were thus determined from the clinical records in the medical service of the industry and checked by means of the death certificates and insurance companv records. The deaths were then verified individually by reviewing them with the physicians in charge of the medical services. In this man ner, there was established a list of cases in which primary cancer of the lung is eon-idered to have been proved as the cause of death A few cases in which lung cancer is strongly suspected but not proved ns the cause of death were considered separately. Mortality rates have liven calculated using both the "proved" and the total of "proved" and "suspected" cases during the years un der observation. Comparisons were then made between the death rates from the same cause among specific segments of unexposed persons. All lung cancer deaths, both suspected and proved, were carefully ana lyzed to determine possible relationship or correlations between the development of lung cancer and any factor known from the clinical records, such as family history of cancer, personal history of heavy smoking, coexistence of a>bestosis, or exposure to asbestos. In addition to this analysis of deaths oc curring in the cohort and during the years under observation, every known death from cancer of the lung, as well as every case diagnosed but still living, has been tabulated and analyzed. They will lie discussed separ ately from those included m the population and time-interval under study, A comparison of lung cancer mortality in the asliestos-produciiig counties has been made with that in counties which are far removed from the asbe-tos mine' and in which, presumably, no a'lv'tos miners live. Finally, in order to broaden the compari son of death rates in different population groups, the rates have been collected for Canada generally, and for the I nited States, according to the mo't recent published and unpublished material Results and Interpretation The cohort which was constructed accord ing to the criteria dc'cribcd in the preceding section has been considered individually and compared with the general population. Description ot the cohort will he presented here as a preface to the results of the study : Original Cohort Ix*st Person-* Deducted Kiti.tl Cohort Living in 1955 (working ,in> Dead hv 1055 Cancer of him: Chiestiunabie cancrr i> Oilier causes l'r.kno*n causes Smokers Non.sniukers Cnknovtn retired) Imife! b.Q9\ 13J 3.95S 5,771 187 S ] 16< t 4,67] 1.26; 2( Tables 1. 2. 3. and 4 present age, number of years of employment, weighted average exposure, and smoking habits of the cohort A comparison of the exposure to asbestos dust is presented in Table 3. All members of the cohort were placed in one of three categories, representing increasing degrees of exposure based on a weighted average of the years spent at various levels o: (lustiness. The degree of dustiness for eacl job category was determined after consulta tion with persons familiar with the environ incut and conditions in the various worl 640 I'M 'IT, June. I')5< HER 0004234 l A LUNG CANCER IN ASBESTOS MINERS Table 1.--Xumber and Percentage Distribution Table 2.--Xumber and Percentage Distribution b\ by Age Length of Employment Are 20-44............................. ........... 45-54.................................... ................ 55-64............................... ........... 65+..................................... ......... ... Unknown........................... . _____ Totals................... ................ Average Are...................... ....... Number 3.901 1,124 615 315 3 - '..95* 41 Per Cent 66 19 10 5 * 10<> * than 0.5%. Length of Employment 5-9................................................ 10-19................................................. 20-29............................................... 30-39................................................. 40-49................................................. 50+............................................... . . Totals............................ A ventre ve&re of employment .. Number 1,795 2.398 922 `4)3 165 56 5,956 18 I'pr Cent 30 40 16 10 3 1 too Areas. I'ur the puri*>ses of calculation, the assumption has been made that the relation ship between these categories is linear, and that Category 11 i twice a> dusty, and Category HI three times as dust}- as Cate gory- I. ually smoking more than five cigarettes per day. Persons who smoke pipes or cigars exclusively were not considered to be smok ers for the purpose of this study. Table ? presents the year-by-year ex perience of the cohort and indicates the Table 3--Xumber and Percentage Distributum by i.xpjsure Category Taw.v. 4--.VuMiki'r and Percentage Distribution by Snittkinn Habits Exposure Category I II............................................ Ill..................................... 1 nknown............................. Totals....................... Average Kxposum................... t.rss n.ia o.s't N'juW^r 2.M,05310 1 772 6 3.968 ;.o I`*t Cmi: 34 3*. 30 * 100 Mnokius Habits smokers............ Nonsmokers..... f tiktii.un__ Totals............ ... l ess Ilian O.S*r. Nun: her t C73 1.2*5 2U Per Cent 79 2l 10t` The fourth varaMv. smoking habit-, was similarly tabulated and is shown in Table 4 This was included because the informa tion iu- available and bccau-e smoking was regarded as one of the \anables which, beside- ;he cm ironmcii!. could conceivable influence the development of lung cancer. As used in this pre-enlation. the term Smoker refers to a cigarette smoker, habit- number uf deaths each year from specified cause-. In general, a case was considered to be "prosed'' a- one of primary cancer of the lung when the records showed that the diagtio-is had been -upi'orled bv an autopsy or surgical resection of the lung with micro-copic examination of the re moved tissue. In on-' case -o considered, however, diagnosis w.is continued bv bron- T VHI K Veur-by-War Experience . / Cohort and Heath Elites pc tin'oiiO Man-'t ears nf Risk ` |'*ar 960.. 951 ............ 952 ................................... >63............................ 9>5564................................... N<- Alive At Bfcnmmc of Year i'MJ V*_-j o.s'1 4Y.Mm0* proved Prunurv C.i.oi l.ime i ti -j i Totals......... . . .......... Proved ' r-tfi' p*r KO.OOO n^:in-v* of risk* 9 y ~--* ,,>5.;i (niv >*f I v.u h :U'|ecu-'i l'rmv.irv a. of Lun.' < 1 hrI -Hl.M't 2 <j 1i T2 " <; it !> -- 3 Il.w L'nknotvu l 1 u n l " -- Man-Years of Risk *,9* V.o2 Vrftt.;- c >o - .T'jtj. ' __ _ 35.J'I * Total" rate per tCO.Onn tn.m-f. w m ri>k = ^--,-~T -- 34.0 Iratm--Truan 641 HER 0004235 I 1/ .1 .i/a;//!'/' i\ ! ' ,'.v/. i / a.-.ii h` I iho. n - .* t ./,v.j .-r /V.'i" .'rv Laniu i.unt. v.% , i-; _ 'l.4 a , *x i, " H IT ..X \.-x Yt\-- \- wY Y~ *>.Y.-v j.* .* ' i. ii * .*. 11 H \r. N;. l uiT vl. t r.kt 1 * r 11* V it il x..i r \\\ <* III v ir ;ti l* 11 vt ; I > .-r. mi <; IU 1 `i-; i* rj *,i \ ,Y* T x-Jli-.V -5. 1 .> M' *1 ,,"J V * ' fA -w Vur-ij.-x \ \ No \\.> Y* * N 1- ............ \M< * V \. YY< >. \\ \ "llM-<-|l|.\ Will i x I'li.ih/atiMii ..i.i ha -y. In another. iillliMU^h the !V ih* .*W"|* x\. rl.c lia^iiM'i x o! i *! -ui.u* e eaim-r nt :hi liintr 't'VlIY U ha-.- heel! ! a ii-ll'l ^Ik'IIMii T!k i tiu xllMuVt ivr t ihe hm !? w : ajltu u %* nitm' x Ml a liieli tin- i!;: t^n* -'i' i\-!i,.iin.- 'i, lion hi hilt 'fU.>. ft the X -. i<telkv \* v': 11 iv * i.f :!n* huii; 1 here Uiia ih l'ii` xlltii I'ii.'i1' The - rt-'l! `n;.m v< ar- Mi -k" ha-X ll'Cli i" mean tile inne.ltei- mi n.eii .-'t I - -1'. ; r !)h- \ . ;.r im Irr . -I.j i A ;[ M | xt Ii! xiiM i;--., -i ih. anrh- ai:: Hi** \ i*.;r wa* c`i:hum1 A t '-ill \ \ .* : r - i - . ir:' >lk \\ IlIM ihcii -1 uruiM- ; h* m ,ti .i* 1 . :uil'i .`x HUr h.! : ^ .1 Ml t!l*\ C.t :* 1 lean; - .... \\Y \ '.1.'^ i al-nr`. IT-.! ,n \ ii <h ; 1 i 11 VT Y ' H t ' x * ii; xj, a. i t > i `ii liei'II |'li MX-ll '' ' .1 t 11 1 *. itv *ivm u ii; ! .11 *ie o II, T l " . i!V xlit 1 lllir ,h .1' 1 . ' -\! ,.-h *1 1 M- < i: . - '1'111 i -t - ' 1 x] <t i ! t. i IliiiiT \ 1. i , - ;. i 1 ;lit ' i " V* -11 *< i.' i 1 ii.* x, -,M;,e, : .i -ii' Hu rJ .. -< - Ml aiU r;;ii; 1 lit iv-llll, t i, , < ^ i . It ~i aiitf iii-i'i ,r h !ui e -Ii, >i "V..,h-\ ran-' whieli (Ti -i< : i . x - i ll 'It ' 1 if i X.ll! l|*K'. !t :,--i;- III.,! - 1 ( . , ( ' ,;:n<l inf tile |in.tei| i- t !i t'l . , . I-A ", \j. ic-l" rale lia-eii Ml'l rile t' ! *1 * ii.,' a >:i I|MlireS !i r tiu- 1 'r<i\ uuir, .1' e ; l,, x1 u m n ia* -T. .hi* l t m 'hi' 1 m-;i> u \ hi, -a.. 1 1111 i ei-jhl tie.ilh-i tl'MlIl IlllILT r.llKiT , < , ; ^ ill, iiIimii. 111.111V. 1111a lYM*' - N- i r ed. 1 f. hint t \ <. r. ilk I i' Mil -i mal ' x'JxJ It CU^l uim'x uc :v in lll'leii. nuTi-a 'lit' lhi ' figure i" 12. ih t 111:; r! t'.llli'l i r. tCIV 1< .-l (II ilk1 '*?' > letc! Ml .'icnii'.caik'c. Hmvetcr. Ii.at i hit Imimi 1 m-t 12 i.-a..c>. ua- arc iimj .al..nc ilu. Ittei .in-! therefore ilk-hv; < >;lk-i' iiwi ai-'-i"- u.uu;' * ! i ` hate a ii'vflu-r 11 ;< r: a I '; \ l'- : 11 it; i-an.'i-r than -Imc- iii< .feller..; j' !-iii.:;n ' em lint he I'ClCCted \ft crtlk-iv-" till tv-ikV Ml' 12 l .1 'X-' ill till' 11111 .k U.-niil .nerea-n- ilk- rate i* > .i [mhiii ulikl; i;-I in mi Ih- llu- -ivrniletch I'.eia'ii'i ilu- tie :'\k n>)< LI* mil . r;. 11: v . u] ihe a i x 1111na1t. Mxl*x III tills i I"'! H'k!'i. XI tl |< - >Kla>: YfiZ i r* Imc then*. w ill \k 5^rl \ H Ivtit . In < 'lit1 ui MlKYl if :ik- f a 11 c -IM'*, ilk 'i: x' iK'li -11 nr J ^ . 1 i>;< at l Ilf \ 1 IV MM'Tlt -'t tali.-ii. -M l 11 '.in>\^ill in a; i!u|*x\ n ,i>. I ri* t . tl i , e rliln il, Mil ilk .,U x Ih.t' <!U:i 1 h \\. .x -!uv .. ! .i i 1 ^ t . i i ' nl` 1 ! I' uvll 1 tlU >u k i i ha'. ;i H' \ ' . a lilt: - x- x -`1 '-Y m!I\ i 1 a !. .1 x(l|M 1 ix^-i 1 1'. ilierenl' n - .,|,i" i rat it c i < In; xi f v , r Ii >h 'll |IT t - flU . k' 1w\ xiau.vale ll-,; .a a MM.."r. iml In iIm-I i, tl'lfx I|f* j" -W'\ ilu !! I'iiix a .it i.r tin. t*a>r i1 x flK 1nf "iT'te.r t .UK'an "1 Ihe luni;. \ 'f > *U' 1 a -i >t i - , or (lift 1 a - hit nn; tlie-l lit l ea-' "i "f I: t ! ro! In . .\ |"i...il.lt .lilt 'a hm e ,`.II.' e r 1 'Ill ae.1,1 Hit t tt.l' TIM MU'ecT Ilia h * ............ a. eXaiiiiTial ion 111 ilk ihir.i . ., ..hlli'tiyll a: .\.i - 'IlhlClteil in auli l|n| . !ui ' 1 ' h. .Ii imi.i - I '.inreell ,-|. Ill \t lletlk-r Unit; . .'.lit.. 1 tv a. ; na t-ni 1 he death tva t"0 rl'rie.l .. - h. 1 \ Tilt; |n't 11 *ltu* Im ehn.nit nit oca.,-(hli- tt nil ne|ihrui- all' 1 ;'iiluii .Hart a iiuiC' lion, am 1 i-.itilv taim f r t; i ihe hint; ( hi till ha si. o I ih e.e faei. 1 xVV m. mittai raniC'l tn inciuilc ihe-e ihiee ea-e- aniony I m:ii 7 " ''is'.v'.af" /Vniincv (uwer / :/u- /.iiw: X*. 1 i \ v> t.. x nn.fti**- Y.*< V ex lAi;UrO \r. im r.kf. in :i.t vr w f-it. Ul U >r. m ( it. rr nv4 111 JV-YI T - V4 u ll-- Vt Auiop> So Y-x No A5bfS!*5lS N.i No r4_> !'.,l 17. June. !<>?.< HER 0004236 LL'SG CASCER IS ASBESTOS MISERS "proved" instances of lung cancer. On the other hand, they cannot, in fairness, be dis regarded completely. It is for this reason that mortality rates have been calculated both ways. Table 8 gives the rates by age groups. The rates by length of employment are shown in Table 9. During the first 40 years of employment, the rate rises, an observa tion which scents plausible since the men were growing older. However, after 40 years of exposure there are no "proved" cases reported for a total of 240 men dur ing the six years, or about 1440 man-years of exposure. When the "sus|iected" cases are added, one case does show up in this Tmile 8--lung Caneer Deaths by Age Gsoups Table 9.--Lung Cancer Deaths by Length t'f Employment Number of Persons and Number of Lung Cancer Death: Length of Employment 5-9.............. . ... 10-19............... ............. 20-29............... ............. 30-39............... ............ 40-49............... ........... M-e................ ... ... No. of Persons 1.795 2.398 922 003 145 55 No. of Deaths ---------------- Prvved Total 00 11 33 57 01 00 Touts............ 5.9M 9 12 Annual Lunu Cancer l>ea(h Kates per 100.000 Man-Neats ot Exposure Length of Employment Proved Total 5-9................ 10-19.............. 20-29.. . . 30-49___ 40-49. . --................ 00 77 54 54 I3h W3 0 90 0M Dw-r-aU___ . .... 25 '.44 Number of l'ertMjn* ami Number of Lung Cancer Dearh. Age Croup No. of Persons Vo. of IViths I'rmel Total 30-41 . .... 45-M. . . 55-M........................... M+ L nktniu-ji ... J.P01 M2i in* MS 3 1 1 4 0 1 3 0 0 Totals....... \y5.n 9 12 Nonna! Lung C'jiKer Drailt Rute> j er 100.Ci") M.n-Yp.ir* oi Kxj>ourc Atff yr-Mip Proved Dni 20-44. ' 4A-54 55-M . 1 nknnwr . il (hi 44 15 44 sl s| 212 Jti5 ( (> 34 : period. Thi- would produce a rate of 6y per lOU/lOO. again demonstrating the im- j portance of these i|iiestiotiable, but tin! proved, cases to the final conclusion. ! because, if there were no cases m this i number of men with long exposure, and if | asbestos is a carcinogenic agent, it must be i concluded that these 240 men have demon strated considerable resistance This is a bio logical phenomenon which has been observed previously anil is consistent with the theory of an intrinsic or endogenous factor in can cer. The only other explanation would be that the susceptible members of thi' agegroup had died earlier of lung cancer. Table 18. which appears later in thi' -ctmii. in- Bsnun-- Tman dicates that the members of the cohort did not die from lung cancer at a younger age than the general population. The rates by weighted exposure are shown in Table If), and it will be noted that they present strong evidence against asbestos being a carcinogenic agent, for, if exposure to asbestos is in any way con nected to lung cancer, we would expect that the longer and heavier the exposure, the higher the rate that would be found. The *nly possible error in this interpretation could occur if the weighted exposures were inversely related to years of employment. 10--Cii>urr [>,tilhs bv Exp`>sur, C tll. t/,try Number of Perseirw ami NutnUr < '( Lung Cancer Deal V.t;>rsure (. ategory Nn.nr 1 VrS'uis No of Deaths -- Proved Total 1 II. Ill . 1. oWuown.. 2.031 2.1 A) 1,772 4 2 U 4 4 4 n Tit.ils.. . V.lis 9 i: Animal I .ung lancer Death Rates per 100.000 M.n-V'\ir;> ot Kx|v>sure K\p>5nr` Category Proved Tot.i T. U...................... m............ Chkiwtwn . ... .. 33 23 10 H -- 25 3a ;u 37 w __ :u HER 0004237 inawuriw ~ -II r~ -~1 rmirTrif!H--wm --rairTTrajsgaMMBy .1 .if. ./. Jiicim/ > or ixin \tki.u. nr.u.ru Table 11.--Xtimber nr Person., :>i I 'urious U'cighted Exposure ('at, a ,r:ej hy Length of Employment ItfUgttl of Employment Weightr*! K*tun* I.UliV'TlvS 1 11 III 5-9 ii* 19 ji>-w U, 39 nny 5ft 4- T`T 4'dt *51 3U :tnj ji: 21* *.37 Tt J'i7 41 24 21 10 Tnmls 2.1)31 Average years of exposure I7.s *J. 1 so !7.> 1,772 (K.t> I'uknown 0 5 2 1 1 * 5 2*) ft lotdl 1.7*5 2.3fts tt* t** 55 L7.5 in which case the heavirst weighted ex posure i Category !lli would -how the shortest length nf employment Table 11. which lists the inmiber of person. in various exposure categories by lutglh of employ ment indicates that this error Inti - not oc curred. In fact, the average number of rears of employment tor each exposure category is almost identical. Table 12. which develops the rates for smokers arid mmsinnkcr.., is most striking. It shows that not a single case of lung cancer developed among the 1265 nonsmokers and that all cases of lung cancer. l>oth "proved" and "'U'pected." occurred in -mi fker. Table 12 was 'o striking that it was felt diar further verihcatiun was necessary. It was possible that some abnormal distribu'ion mav have occurred, e g, the iioii- I' mile 1.1--\umber mij I Vr,, iit,i.,v / 'istrih-ution f .smokers ontl X onsmokers by C,roups 8iie Group 20-44.. *5-54. ..V-64. . . . '*+... 'uknown.. .. Totals.... Average age.......... Number 3. jum >,l 411 *.4 t.oT'i s:\ jnj 4 .'nill I.2ft5 44.2 t'nknown 12 l 1 2ft 40.7 Tviiie tg- Limit t me. r 1 >. ur/i for Stn- k'.'r.i itmi A ' 'ifMn-'iiTj N'umlier <t lVron. .uni Nuti.lrr <t I.mu* <l aiKrr 1 Vjilis. la >nv>kn.i; No. of LVuhS 1Vr***n$ ProwiJ Tot U ^iiirtkeis ... Non smokers l :.kn*>tvn . *.`.-73 *,* u 2n u 12 0 o Totals 4.'5k y 12 .\nrmnl T.mw O.tm+r Dru't K.i ;<r lu'Mioft M.m Vr tr^ nf F.tfuKiire h-. ookinc ff.irni N. i if IVrllh* 1 -t ll >mnkcts....... V*ii>ir:nkiu>....... 1 nknnwii.................... overall__ 'A 2 V i. "" :w -mokers mav have included i larger percentage of voting men li.iisn' licmlv . ad dilioiuil Tallies, la. 14. and 15 V\v`1V oli* structed to show the distribution . ii *ninkkT> and nonsmokers bv age. length i f eillplovinent. and degree of exposure. Although there are slight differences, thev do not account for the fact that all obsc rv ed cases of lung cancer were in smoker-. In li spe.t to age fTable lai the combined average age ot the smokers \v.'i 4.`J tear:- les. ill.ill that of the nousiiioker s. Table 14 shows that as far length of empli.v ment i- con- Tahi y. 14 -- A uiulu'r 'inti 1 Yri ii / >r.v\Vi/'U/i.*i "f AWfXvrv ,7mi \ otf*>U`>k\rs : v of /. ii^/'ivmfir/ fxuictn of Kmploytn**ut .5-0 HV-tP. . . 20-29. . . .KK4!> M1-4M............. 50- ........ T-'ials.......... Average length of employment.......... Number m'*k<*rs NonMui.ker? l.lo* J77 i # : 420 722 my 13.1 75 .<.< -i.n;:i i ;2,'0 17.n P.J.3 f'uknown 1ft 4 2 4 0ft JO Ift.ft r'eroentuire Distribution \ge Group Smoker Nonsniiiker 20-44.................... 45-54.................. '>4-64...................... 05+........................ . Unknown...,. ... tkv5 19.2 M 3.5 .'4.5 17.7 I6.U 11.8 0.U Totals... 400% 1110% 1'nknown *>.o 21 i.O 10.0 4.0 . 7.0 100% ` Iss tlian 0.05%. hXl CrrconMce Di.irihuiiun I^enclh of Employment Smoker Nonsmoki'r 5-9................ 10-19...................... 2U-W........................ 30-39.......................... 40-49............................ MM-............................ 30.1 42.1 15.4 9.3 2.4 0.7 29.5 33.7 15.7 13.1 5.9 1A Totals......... I0U% 110% fuknmvn Ml.ft 20.1) Ift.ft jn ft 00 0.0 ino% I "of. 17, June. l'tyX HER 00.04238 lung cancer in ASHIiSTOS MINERS Table 15--Number and Percentage Distribution of Smokers and Nunsmokrrj by Exposure Category Ex{*osure Category I n. .Uinnkn. own ToihL*__ e*K<Mre i-ateporv ..... .Number .^niMk^rj N'ousnmkers 1.5.VI 474 i.oVi 452 : .42.*. 3M 1l 4.H73 1.265 1.9 Unknown 4 7 9 0 20 2.3 fvnvnuise Distrhurwui Kiposun f.ate^ury -Mimkrij* Nonsniokcr* [ .i3 2 37 11 :*h.2 35.7 in . . .,> ( nknown *..I Total*...... U7c 1"'% Unknown 20.0 35.0 i5o u.u lore c>*-ned. !ii<- >mi>krr> had worked about 2.5 x-ears less "ti the ax-eragc than the non-moker* With lunger exposure ;m<I greater age. vine would expt ct the nonsmoking group tc 'how a hitjln r rate it lung cancer were due to .t'be'tos I able 15 <hnw< that the average exposure category wa- almost the ',iiiu fur tlie two groups Therefore, this \ .inahlt 'eeui' to he "1 no importance n amounting tor this diltcrenee. The re-tilt of ibis additional analvsis is that not:i of the~e factor' appeal'' to lessen the i ttt. T i t 1 aha' 12. ( - aa ta / tire tt.' I.xrerience :eith //air / the /'r "fi/icc '/ Uuehec, ['<- minion i. amnia. and the ( >iil-'<i States --- In onj, ' 11* make a compari'Oti of the i xpera o. , .uimng a'lic-to' miner' with that r- :al population of the I'rovmce nl tjiieh, , ; iti'tii' x\ere gathered. a> Mated e.urucp tla oftice of tile I )i\ i-i<>ii of Demography m the Provincial Ministry of Health. The data on total deaths, deaths from all forms of cancer, and deaths from cancer of the lung were obtained by sex and by county for the years 1950 through 1955. In addition, all death certificates which specified primary cancer of the lung, and all those which indicated lung cancer but did not specify the origin, were exam ined for the years 19.S2 through 1955. Table 16 gives a tabulation of the number of deaths from lung cancer in the Province and in the cohort for the years 1950 through 1955. and shows the annual rite per 100.000 in these segments. It will be noted from the table that the mortality rale for the "proxed" cases in the cohort is only slightlv higher than the rate for the Province. When the "suspected" cases are included in the calculation, the rate for the cohort rises to 35.8 fer l<K),(HX). which is about 50ri higher than the rate for the Province. This, it will be recalled from the previous dis cussion of the effect of the "suspected" ca>es oil the results, approaches but docs not exceed the significant level. (hie further interesting observation from Table 16 is the rather marked increase in the total number of case- for the Province betxxecu !'*50 and 1<J55. It is assumed that at least part of this increase is due to im proved recognition and reporting of lung cancer during the interval. For this reason, the years l`-*5-4 and 1955 were thought to be more nearly representative of actual condi tions. Kxen so. ir is quite likelv that the general imputation U not studied for lung cancer xxuh rhe s;iine diligence with which 'I' ut; l w* - c p.ir-sufj >/ (r* ith Province <>] QuC^CC --- \umier it r*rMi' 1.11112 itu.vr IVifhs Annual ih: i h.i'tJ 1954 Kttrc p**r I'.IW Torxl uw.ooo >jo i 'hnri I'otai Vro\*-i : 9>.t .( o ti i j t* Province i`i;i 215 2*5 ' excluding w-i***' - uork^ry 3*3 r.; 1 '24 3 2 1 t i 1u2 :vr2 .3V4 l,r>l2 22 13.S 23.3 22.5 i In the nr** fitrii'ps, :* issumed ill n|r Itin* cancer death5 ar*> for men of 20-*- \ear<. I Approxnrufr midpoint "f th** eimtueraiwi population for W*t. and the estimated populanon for 19T4 'Rapport. Div.de la De- JtuotrHphic tNumlwr ahw m r.p-ri u l^iamnc of 19VJ. Fraitn -- HER 0004239 iM Aye Group 30-44 45-54 \v-M 65+ Totals A. M. A. ARCHIVES OF 1KDLSTRIAL HEALTH TaHi.t 17.--Lung Cancer Deaths for the Prcnmce of Quebec l.stmiaicd t population TTT.rvm jir.'.im* 137.1MI IJl.OUU i.33:.unu Number of Deaths WA Total Cmiflfil Total Proved specified Primary Total lYmtird >lcifl*d Primary ------------------ - --- --s---- ------- -- - -- . Total iToved Total Prmed Total Proved 17 13 11 9 IT IT 9 io6n7 36 38 43 t* 26 32 u: V, 32 Uo 17 111 33 51 14* *4 Us M 395 120 191 99 342 IV. 337 152 Ate Group 20-44................ ................. 45-54............................ .................. 55-64............................. .............. . 66+................................... .................. Over-ail......... ................... .................. Death Rales per 100.000 1954 Total Certified Specified Primary Total n > 33.2 73.0 91.7 Pm'vd 1.7 17.S 27.7 27.3 Total 1.4 21.3 50.4 56.2 Proved 1.2 14 4 23.4 24 0 23.6 9.7 15.4 4.0 i 9.'o Total Certified Total *> ! 29.7 45.4 122.3 Proved >2 *7.3 41 .* 44 27.6 V* ' Specified 1Primary Total Proved 2.2 27.7 M7 122 3 1.2 15.4 418 4.e 27.2 12.3 * Data from death certificates. t Estimate for population obtained by applying 1851 percentages for age groups for males to the !>(;! i**pnl:uion for 1954. as cum to RappoTt, Div. de U Demography. this disease is looked for in the miners, and it seems probable that the mortality rates for the Province may be low. This would appear to be substantiated by the fact that the reporting of cases in the cohort showed no such increase over the same period. Table 17 was compiled to show the an nual age-specific lung cancer rate of cases in which the death certificate merely read "cancer of the lung," as distinguished from thosC in which the diagnosis ua confirmed bv autopsy, surgery, or biopsy. The term "specified primary refers to those cases in these two categories in which the tumor was specified as having originated in the lung. It will be noted that, of the total cases reported in 195?, a much higher percentage than in 1954 were specified as primary. The table also shows that a higher percentage of the total cases certified in 1955 were proved, again indicating increasing interest in this disease. A comparison has been made between the age-specific rates shown in Table 17. and those for the cohort, shown in Table 8. An average of the 1954 and 1955 rates for the Province has been used, since the 1955 figure was higher and may have been ex ceptional. This comparison, summarized m fable 18, shows that the observed number of deaths in our sample is not significantly greater than the expected number of deaths, based on the average of the 1054 and 1955 figures tor the Province. It is true that, in the case of the age group of o5 and over, the five deaths provide a figure which is almost significant at the 95' '< level. How ever, it should be noted that this number includes one of the suspected but unproved cases previously reftrred to Furthermore, it is rather likely that the rate for the general population is understated in this age group, for the obvious reason that the exact cause of death in the verv old is not T.vw.f. 18--Comparison of the Admit and Expected K umber of l.un,/ Cancer Deaths by Age Among Asbestos Miners Arc Group Province Total Specified Primary Rale per IOO.OUO 20-44 45-54 5.5-64 654Vn known 1.8 24.5 67.6 89.3 Ohserved No. Etpocred of DeAlh? No of No. of Miner? Deaths Proved Total 3.901 1.124 615 315 3 0t l 1 l3 2 33 4 *i 00 Theeipocied number ts based on the averare of the 19M and 1915 aee-snedfic rates tor the 1`rovmce o( Quebec, t Actually 0.4. 646 !'ol. IT, June. PciH HER 0004240 .]1 i.UXG CAXi ER IX ASBESTOS MISERS Table 1*).--Age Distributu'm of Adult Males for Table 20.--Annual Death Rates per 100,000 for the Province of Quebec, 1951 * Cancer of the Lung in Canada Age Group 20-44.................... 45-54.................... 55-64.................... u+.................. Tout........ fnivnicc ---------------------- TVrnmau \*uin**r Percentage in Cuhort 727.135 l;o.95*2 128.944 L13.4G7 63 16 11 10 in 10 5 UM.4W 100 100 * Rapport, 1944. a matter of the same intensity of interest as it is in younger iicr-nns. Table 18 also .m-wers a question pre viously raided, it -hows that the members of the cohort have died from lung ran ter at an age earlier than the general popu lation. and that -itch .m explanation cannot e offered fur the absence of lung cancer n 240 men with more than 40 years of Nuployment referred to on jiage 64.1. Before leaving this comparison of the Province w ith the miner-, it should be shown that their age distribution- are reaionably the -ante. That this i- the case can ie observed from Table 19. It should fie remembered that the miners etire and con-e<|uently. it can be expected hat the oldest age group will be larger in he general population. '1 lie data presented n Table 2C indicate tfiat the lung cancer ate generalk dei tease- after age 70, Thereore. w<- could expert the rate for all people tver Os to be -mailer than the rate for the 'roup i,tween to and 75. which would applv n the ulde-t group of miners It is felt hat bv u-ing the whole adult male pnpulaioti \m have developed rates for the gen eral population which are somewhat lower han if we had been able to exclude the (triple in the general population over 75. : A comparison betw een the aslxrstos minerhd the population of the Dominion as a fhole was made, using statistical material font -everal sources. Jn one source. Philps 79 gave age- anti -cx-specitic rates for anada for three periods between 1931 and ?52. The rates for males are given in able 20. These figures show strikingly the increase , rates between 1931 and 1952. and this Age Group Under 30 30-34 36-39 40-44 46-49 60-64 65-59 60-64 65-69 TO-74 76-79 80-84 85+ All Ages I93M933 0.2 0.9 2.0 3.0 3.2 8.2 12.7 12.5 15.1 lo.; 15.8 8.2 11.4 2.8 (roupsof Years 1941-1943 04 0.9 34 5.4 12.5 18.9 27.0 33.7 34.5 30.6 30.0 27.9 14.3 7.1 1950-1952 1.0 04 3.0 64 16.7 374 50.7 774 102.9 86.3 83.9 59.7 71.0 15.8 "Mortality from Lung Cancer m Canada." 1931 to 1952- increase is particularly marked after age' 50, confirming an observation previously made, to the effect that until recently lung cancer has probably been underdiagnosed itt the older age groups in the general popu lation. To use these figures for purposes of comparison, it is necessary to combine the rates for certain age groups in order to conform to the age distributions used in this study. Since the exact populations in each age group for the years indicated is not known, this must be an approximation. However, the rates would be somewhat as follows: Ace Orn-jp J5A4 65 4- Rate j 27 pi >ft.0 5 "l hese rates are. in general, lower than tho-e developed for the total fproved and -itspected t case- of lung cancer among the ashe-tos miners. I he ottlv large difference, however, is in the age group of 65 years and over, and it is quite po-sible that the rate for this group may have increased for Canada between !52 and 1954 as it did for the Province of Quebec (Table 17i. A further comparison has been made with an over all rate obtained from the American Cancer Society for respiratory cancer deathin Canada in 1953. This rate, for males, i- 20.8 per 100.000. or more per 100.000 than Phillips' 195*1-1952 rate, and compares with 25.3 per 100 Of to for proved case- and 33.S per 100.000 for total cn-es among the aun--Truan HER 0004241 M7 A. M. A ARCHin.S Of iXIH'STRlAI. IU-.AI.TH Table 21.--Number of Deaths and Death Rates per lOOflOO by Age Croups for the Adult Male Population of the United States Age Group 20-44 45-54 45-61 + Tout Population 24,M4.00H VU65.0IV 6.34O.000 5.470.000 44.412,000 Cases 883 2.279 0.254 8.483 16,599 Kate per 100.000 3.6 36.9 98.4 114.3 37.2 Data from * 'Vital Statistics of the United States." Vol. 1 and 2. 1952. asbestos miners in this study.. It is therefore obvious that there are no important differences between the rates for asbestos miner? and those for the general population of Quebec and the Dominion of C anada. Since it is probable that figures for the United States are more complete and. there fore, possibly more comparable to the data for the miners, age-speci6c rates were com puted from "Vital Statistics of the United States," Volumes I and II, for 1952. These rates have been tabulated in Table 21. It is apparent that these rates compare favorably with those for the asbestos miners as shown in Table 8. Still other rates for the United States were obtained from the American Cancer Society, and for males, these were 25.3 per lOO/XJO in 1953. and 28.0 per lOO.OtX) in 1955. They are not identical with the rate calculated from the figures of the office of Vital Statistics, but this is i>0'sibly because the American Can cer Society rate- are for males of all ages. Nevertheless, they. too. compare favorably with the rates of 25 ior 34 for total cases i obtaining among the asbestos miners. Turning for a moment to a comparison between the asbestos miners and persons who are exposed to asbestos in one form or another i as distinguished from the gen eral population groups just discused, who have no exposure I an interesting observa tion can be developed bv deduction. Hueper 58 has stated that there are about 35.000 persons exposed in the United States, and we have found that the Canadian mines employ about 8000. Elsewhere, it has been estimated that the workers in England who have exposure total between 3000 and 5000. With workers in Africa. Denmark, Nor- way, and other countries, at least 5U.U0O persons must be exposed throughout the world, and it can be assumed that this number has been fairly constant in the 20 years since 1935 when the first case of usbestosis with lung cancer was rc|K>rted. At least 1,000.000 man-years of ex|tosure has thus been accumulated, and this figure can be divided by the approximately 150 cases of lung cancer with a.sl>estosis re ported during the 20-year ieriod. This gives a rate of 15 per 100,000. which is at least indicative that any lung cancer rate which can be calculated fur workers ex posed to asbestos dust > not much greater than that for the unexposed imputation. Comparison Between Eight Counties Ad jacent to the Asbcstos-}>rndueintj Areas and Eight Selected Counties.--To ompare lungj cancer mortality rates in the own ties siir-j rounding the asbestos-producing areas with another group of counties in which no as bestos miners are likely to reside, the rate: were computed on the bads of figure* fo^ the years 1950 through 1955. The vighl counties selected for comparison were Arj genteuil, Chateuiigay, Montmagny. Port neuf. kichlieu. Riv iere du-l.uup. St Hyacinthe, and Terrebonne, mamlv beeausi they represent a wide geographic distribu tion throughout the Province. The cuuniie selected because of their proximity to thj asbestos mine* include Arthabaska, I'eaucq Drummond, l'ronienac. Megantic. Rich mond, Sherbrooke, and Wolfe. Table 2 shows the number of lung cancer death for the years 1950 through 1955 for eac of the-e counties, and a mortality ratq based on the adult male population in 1953 l'o emphasize the comparison. Megantil County ha< been shown separately, as hat the Prov ince of Quebec and also the Proy ince with the eight "asbestos-producing counties subtracted. F'.eeause of its uniqij lung cancer death rate, Montreal et Isle <J Jesus has also lieen listed in order to provifj further comparison. j It is apparent from the table that tl lung cancer death rate for the eight countii 618 HER 0004242 I'ol. 17, June, 19 MP-T* LCXG CAXCER IX ASBESTOS MIXERS Tabi.e 2J.--Xumber vf Lung Cancer Deaths and Rate per 200.000 Man-Years Tourings Megantic Countv Eight "Adjactni" Counties Eight Sflectrd Counties Province o( Quebec Province of Quebec less enrht "adjacent" counties Montreal et Isle <Je Jesus Adult Male . " -- - population 1932 1930 1951 13.100 3ri \ 3 <i.noo 2 10 196 220 l.infi.irti 190 217 394.1X10 a * Male Lung Cancvr Deaths * --- - - -- - . 1952 1953 19M 19.V> 33 l 4 16 4 16 5 18 5 y 243 303 303 337 23* 287 29V 341 156 192 185 235 It is assumed Mini all male Inns etneer deaths occurred after age 20. -------- --- Rate per Total tnn.oho 13 16.9 M 94 49 9.8 1624 22.6 1370 23.8 770 32.3 immediately surrounding the asbestos-pro ducing areas is practically identical with that <if eight counties selected for comparison. While Megantic L>`ttiily has a rate nearly twice that of the combined eight selected counties, it i- lower than the rate for the Province, and considerably lower than the rate for Montreal. The figure for Montreal would certainly be higher except for the very low numbers of deaths reported for 1950 anil l((5l and it would appear that in those years some error in reporting has undoubtedly been made. On the basis of the other years. lOsd and 1151 deaths would be expected to be aUuir 200 greater. This would result in a rale of 40 per 100.000. The only possible conclusion from this comparison is that there is no evidence that the persons who live and work in the coun ties surrounding and adjacent to the as bestos-producing areas have any greater ! incidence of lung eancer than (hose who live elsewhere in the Province. J Comment / .(!! Recorded Lung Cancer ! Cases. ! ivitxi and Head, among the ,-isbcsI ins Miners - Although a simple enumera tion of all the known or suspected cases of cancer of the lung in these areas has no particular value from a statistical point of view, it i' of interest to summarize such cases for the record. There were nine deaths prior to the beginning of the time period covered by the study, including one in which the diagnosis was mediastinal lymphosar coma. During the period covered by this investigation, there were nine proved eases and three suspected cases in the cohort. Through 1956 and to date in 195". there were eight deaths, mx of which were merely suggestive of cancer of the lung and in cluded such diagnoses as mediastinal lymphosarcoma, mesothelioma, cancer of the leg with metastases to lung, abscess of lung, and cancer of the pancreas. One other was diagnosed on the basis of x-ray only. In addition, there are now living four cases in which the diagnostic evidence is strongly suggestive of lung cancer. This is a total of 33 cases of all types, including 10 "sus pected" hut unproved cases, and 4 that are still living. The remaining 19 constitute the total of proved cases of cancer of the lung among the asbestos miners since 1940. The proved cases averaged 59 vears of age at death, and varied between 37 years and 68 years. Their working span covered periods varying from a minimum of 14 years to a maximum of 37 years. Only three men had less than 25 years of em ployment in the industry. Seven among those on whom such information is avail able had a weighted exposure placing them in Category Til. and six worked in an exposure represented by Category I. There were only 17 among these proved lung cancer cases in which we have in formation regarding the presence of asbestnsis. Asbestosis was present in nine, although it was minimal in two. Two path ologists disagreed regarding its presence in another. At least seven of the 19 proved lung cancers, therefore, were not accom panied by asbestosis. Summary and Conclusions Interest in the question of whether there may be an association between lung cancer Braun--Tmatt 640 HER 0004243 A. M. A. ARCHIVES OF tSDLSTRIAE HEALTH and exposure to asbestos has been evident since the report in 1935 by Lynch and Smith of a case in which lung cancer and asbestosis were both present. As additional cases in which the two diseases coexisted were reported, a causal association appears to have been gradually accepted by many authors, although some workers considered the correlation to be inconclusive. The pres ent study was undertaken in an effort to de termine whether a causal relationship did, in fact, exist between exposure to asbestos and cancer of the lung. Since most earlier studies had been limited to enumerating the lung cancers found in certain selected samples, such as cases coming to autopsy or death certificates in which asbestosis was mentioned, it was apparent that they could not fulfill the re quirements of an epidemiological and sta tistical approach to the problem. The present study was. therefore, designed to meet the requirements of this method. After a preliminary survey to explore the availability of reliable information, data were gathered on workers in the asbestos mines in Quebec, based on their medical records. A cohort was defined as a group of asbestos miners having at least five years nr" exposure and who were in the industry in 1950. Data relative to their characteristics were collected and their status at the end of a six-year period of observation was de termined. In the case of those who had 'died, an exhaustive search of death certif icate:- .utd insurance records was carried out in order to determine as nearly as possible the exact cause of death. Mortality rates from lung cancer for the general population of the Province of Quebec and its various counties and for the Dominion of Canada, as well as the I'tiilcd States were calculated from statistics collected in the appropriate places. Comparisons of the rates obtained for asbestos workers and for the other popu lation groups were made according to ac cepted statistical methods. Records were obtained on 6091 persons who fulfilled the criteria of the cohort. It 650 was not [>ossihle to trace 133 of these for the whole period, but 5771 of the remaining 5958 were found to be still living in 1955 or later. Of the 187 known dead, cancer of the lung was considered to have been reasonably proved in 9 and to be strongly suggested in 3. The members of the cohort were studied with respect to age, length of employment, a weighted average of their exposure, and their smoking habits. It wa found that 4673 were smokers within the definition of that term as used in this <tudy. Thirty-four per cent of the cohort were more than 45 years of age. and thirty per cent had been employed for longer than 20 vears Thirty per cent had a weighted exposure which placed them in the category of highest ex-! posure. ' The mortality rate for lung cancer, a-q computed on the basis of nine 'proved"! deaths among the cohort was 25.3 per 100,-! 000. When the three "suspected" case' were, added, the "total" rate for the cohort rose: to 33.8. The importance of the suspected; but unproved cases in determining these rates has been reiterated because it is likely that such cases would not be included in. the statistics for the general population and1 because thev influence the results so mark edly. ' 1 According to the findings in this study, the mortality rate from lung cancer does not appear to increase with length of ex posure or with degree of exposure, a fact which presents strong evidence against the earcinogenicitv of a-lx:-ans. Comparison of the experience among the asbestos miner.' with that of various seg ments of the unexpo.-ed. comparable popu lation shows that the observed number of deaths among the miners is not significantly greater than the expected number. The rate for proved cases among the asbestos miners i 25.3 per 100,0001 compares well with the rate of 22.5 per lOO.Omj for the rest of the Province, and 20.8 per 100,000 for adult males throughout the Dominion of Canada. It also compares satisfactorily with rates /'./ IT, June. WiS HER 0004244 LL'SG CANCER IS ASBESTOS MISERS of 37.2, 25.3, and 28.0 obtained from various sources for adult males in the United States. Finally, in this matter of comparison, it would appear that the world-wide experience of persons exposed to asbestos dust is not worse with respect to lung cancer than that of the unexposed population. The counties surrounding the asbestos- producing areas, in which it i> presumed most of the asbestos miners live, have al most identical mortality rates with those of eight counties widely scattered through the Province, and arc lower than those for the remainder of the Province. and much lower than the rate for Montreal. Since 1940 there haw been IV cases in which rite diagnosis of primary cancer of the iung mac lie inii-iilered to haw been proved Approximated half of these ca-es were a"' tinted unit ..diolo-U, .Ml hut one died in tin recugm/eri 'Yamer-age and at K-.t-r air til! r,I h.ui nth '.he llghteSt ex- i-M-v.r.- (. .lit Of re 1 ' *o * .asjles), ,s ihis t. t )|i Ilk b.l j r w hat at'e 1,,'hewi 1 to he O l i ]| Hi It ; m i < 1 r liable data, it -cents fair in < 'Uxkaif th.i ; til,- 'siie-tii' miners in the 1 ` v mo *r Ollehv v tin iml have a signif- IvVltltlv i:; irhc r i Ira th rate from lung vaiit'fr til.it: J. aiii ,:liir M gment' nt ihe guts i al P-'i'-'da ' \ *i ! ur ilk Jearii rate fro!'i: iuii^r hi, 1 : ' iu l .1 - (' iingu-uis t" the t .s up, ! -11 s 1 ' 11 mil i.uahle ft, that in areas .. 'li !\ :!!< If. i illmt tghniit the- I'ritv iih'r uf < Jlltd'V i.^ - !- t ! than in -" Ue in fan- i7cl 1' - * :li 1: Air 1 'n i\ nit e REFERENCES 1 C..-' 1 'O'iuT-. i\ Bn :i> in.tl Carcinoma: P i 11 a _'un i i-<-. i I iin rnm ( oil Surcreoils -Vi .',"5 S' I" I pop 3 An<r- M 1ou'liioetiiit' C trcui1 i A-- ' i. 11 >- I <I 3 * -ini' ut... .. :i. ,i ot i,, kei'on of J :t,: ii.-Jj,, ,?4; . \,,v , p,.u I' \ 1 'lurtitteuv. to the "! V-lfsi. \-. T.w jirn;,.; pi 5Sl, .-'C. 1'4`t i 4 Anders,. t S i, ,i liit u. J H Silic -is ! and C .uvear h I "Tie. J live 33185-214 (Marti,) ' 5 lla.ut' 1 \.1" -11 -I-. 1 Viii-dic ns .I Mchmrhr ( -i (. - 4i- M u , i. ; r i ! 1 Co B'JIOl----V i nil: 6. Behrens, W.: Experimental Asbestosis, Schweiz. Ztschr. allg. Path. 14:275-297, 1951. 7. Behrens, VV.t Jr.: The Clinical Picture and Pathology of Asbestosis, Ztschr. Unfallmed. u. Berufskrankh. 45:129-140 (June 15) 1952. 8. Berblinger, VV.: Increase of Lung Cancer and Diseases Due to Dust Inhalation. Med. 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