Document GmVRRg2YDnMK5RO2gQYep607x

Braun and Truan Published Paper Exhibit No. T-142 Date: June 1958 Description: AMA Archives of Industrial Health, 17:634-653. An Epidemiological Study of Lung Cancer in Asbestos Miners Published Conclusion: "On the basis of what are believed to be complete and reliable data, it seems fair to conclude that the asbestos miners in the Province of Quebec do not have a significantly higher death rate from lung cancer than do comparable segments of the general population." Deleted from Draft Conclusion, p. 76: "Despite this, the results suggest that a miner who develops the disease asbestosis does have a greater likelihood of developing cancer of the lung than a person without this disease. We suspect, however, that under-reporting of asbestosis cases had led to a fallacious finding in this connection." [emphasis added] Reprinted Irani the A. Sf A. Archives ol Industrial Health June 1958, Vat. 17, pp. 634-453 Copyright 1958, l>v American Medical Association ' . wn FROM Wf I j| If II PWlNTII+'S EXHIBIT 'Is , T'/<-/2 An Epidemiological Study of 4400 Fifth Lung Cancer in Asbestos Miners Pittsb- F0UNDATI0N "rh 13, Pa. DANIIL C MAUN, M.O., m4 T. DAVID T*UAN, M.A., PHtsbiirfli Ever since the pronounced increase in the incidence of lung cancer among males became apparent, there have been attempts to associate it with one or another of the various elements in the environment of man. The approach used by some workers has been to suspect one or several sub stances and then set about in an intensive search for lung cancer among persons who have had any exposure to those materials. In this connection, Smith42 writes: "The tendency of authors reporting the coinci dental occurrence of primary lung cancer with silicosis or with any other theoretical etiologic conditions, has been to emphasize the percentage relationship in extremely small series of cases, with control cases which are not in any way comparable." It would seem inevitable that asbestos should come under scrutiny in this manner, because prolonged exposure to this material is known to cause a specific type of pneu moconiosis, and because persons who show this form of pneumoconiosis often come to autopsy and provide a ready source of material for study. It was in this way that reports of the simultaneous occurrence of lung cancer and asbestosis began to accu mulate alter the rejort of a case by Lynch and Smithin 1935. Within the next 10 years, about 15 additional cases were re ported, and in 1954 Merewether 78 reviewed all deaths from asbestosis recorded in Eng land since March, 1924. Lung cancer oc curred in 165c of these cases. Gloyne,81 Accepted for publication Jan. 20, 1958. This study was made possible through a grant from die Quelnrc Asbestos Mining Assignation. Medical Director (Dr, Braun) and Statistical Consultant fMr. Trims), Industrial Hygiene Foundation. 634 whose work is also frequently referred to as establishing a connection between asbes tosis and cancer of the lung, reported in 1951 that cancer of the lung was present in 14.1% of asbestosis cases examined by him. In 1941, Nordmann and Sorge78 claimed to have produced lung cancer in mice which they exposed to asbestos dust. Since 1951, additional cases of cancer of the lung coexisting with asbestosis have been reported, and, according to HueperM about 100 such cases had been reported up to 1955. As a result, an association between the two diseases appears to have been ac cepted by many authors, and several writers were using the term "asbestosis cancer" of the lung. Werber,** in 1952, stated cate gorically that in 7% to 17% of cases of asbestosis, after a latent period of about 1 Ys to 20 years, carcinoma becomes estab lished in the lung. On the other hand, not all authors ac cepted this alleged association without reservation Saupe 80 in 1939 reported that he had discovered uo cases of lung cancer among 620 cases of asbestosis which he had examined; and in 1942, Holleb and Angrist ,s expressed the opinion that the number of cases of asbestosis with lung cancer was loo small for statistical evalua tion. In 1947, Wegelius 88 reported 126 radiological!)' diagnosed cases of asbestosis among 476 workers in Finland, and found no cases of lung cancer in this group. Goldblatt and Goldblatt in their section of Merewether's latest book,44 state: "But at no stage in all these impressive researches was any clue obtained which might have offered any supjwrt to the possibility that asbestos could act as a carcinogen. There / r/jl O Qs H /.CAC CANCER IN ASBESTOS MINERS is no reliable criterion by which one cais .uiticijMlc carcinogenicity and, as is well known, relatively minute changes in the structure of a chemical carcinogen are suffi cient to diminish or eliminate carcinogenic action. If asbestos is indeed to be regarded as a carcinogen, the need is felt to demonstrate some property which can be regarded as something more than inertness." These authors advance the theory that, until some more experimental evidence of direct carcinogenesis by asbestos or a de composition product of it can be obtained, asbestos might be considered as a "eo-carcirrogen'* wfifcfi only induces a' further de-' velopment of a preneoplastic condition brought about by something independent of (he asbestos, such as an endogenous factor. Thus the literature, while tending to sup port the thesis that asbestosis is in some way related to the development of lung cancer, is by no means unanimous. Alto gether, it is perhaps more confusing than enlightening. A careful review shows that the majority of the reports are clinical and not epidemiological. They lack many ele ments necessary for the application of epidemiological techniques to their content, and most of the authors do not make claim to having done so. What has happened is that succeeding authors have drawn conclu sions* arref generalized' beyond- the scoj/e of the works which they quote. Nowhere, for example, have we found references to a population of asbestos workers, although several authors who have quoted the ob served incidence of lung cancer m autopsies of persons luho also had asbcs/osLS imply that this incidence applies to asbestos work ers, generally. We have likewise been unable to find any study which actually calculated the incidence of lung cancer among a population of persons who had asbestosis, and not just those who came to autopsy. With the exception of a paper by Doll,25 none of those reviewed gave anv data on cX|>osure and dust concentrations, and even Doll's paper merely mentions "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 dusty." . There is, furthermore, a complete lack 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 radio logically detectable condition. Most of the published reports obviously included women among their cases, but some of them do not give the number or projwrtiem-of' wowien 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 Hnq>ers* in 1955, only 10 ap[ear to have originated in the United Stales, and 7 in Canada. Sonic of the earlier reports apjvarently included asbestos miners, but it can be assumed, since 82 of the 99 cases had originated in England, 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 historv of cancer, length of time in the industry, and age o? the individual case are also- notably abxmr in the*majority of these reports. With this understanding of the limita tions o; the existing iiterature 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. One of the most detailed studies and one which deserves the most serious considera tion is that reported 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 bv studying records of men who worked for at least 20 years in exposed situations. B roun--Truan /V 6J5 .4 M a AR<.nni.s 01 ixnrsTKiAi. hi.ai.tii Dull 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 [Arsons potentially exposed to asbestos dust in the United States alone vary 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 vears, the study automatically excluded those who died from other causes after shorter employment. Another reason why this publication is if importance is a statement which it con tains to the effect that "the strongest evi dence that it flung cancer) may be a hazard (in asbestos workers) has been produced bv Merewether and bv Gloyne " In lb 51 Giovne11 presented a review of 1203 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 14.1% for lung cancer among asbestosis cases coming to autopsy. There were in his series 796 cases with sili cosis, and 6.9% of these also showed pri mary cancer of the lung. The incidence of lung cancer in other forms of pneumoconio sis vyas 6-7%. and in 169 cases which proved not to have any type of pneumo coniosis it was 8.3%. Gloyne considered "the mortality of the asbestos workers" to be "disturbing." First of all, it is obvious that the paper does not deal with the "mor tality of asbestos workers," and secondly, it must be borne in mind that all of Dr. Gloync's cases 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, in 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 [>oints out that the rale for lung cancer based on necropsies at the London Chest Hospital was 21.3% while the figures of the Registrar-General showed only 2.4%. He thus recognized that autopsies on a cer tain selected group of cases were not rqresemntive 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 hint. All that it really shows is the fact that in a group of 121 caw. selected for special studv pri marily beenuv"they seemed .*bi**wm;d bv prelimmarv examination. 17. or 14.1 r) . had lung cancer Mcrow eliter ' ' in 1^47. m ihi riqmrt of the L'-'r' i i y ,i. v.; 11 r o". I'aciunes. reviewed all caw- re|Kirted between 1924 and 1946 in which asbe-tosis 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 males and 139 females. Among them were 55 cases (16%) of cancer of the lung. 41 in males and 14 in females ft is quite possible that a large number of asbestotics who did not die of their asbestosis, or in whose 636 I'ol. IT, June. ;w.v G-v/ Y-*- o I.C\C CASCr.R IS ASISESTOS MISERS death certificate it was not mentioned, may prior to that date and enumerated a total have been missed. The import of this 16% ` of 99. Eleven of these were those dis is enhanced by the simultaneous statement cussed by Doll ** and may have been cases that the incidence of lung cancer in autop covered by other authors. Eight were dis sies of the general jiopulation is only 1%. covered by Kennaway and Kennaway " in The danger of attempting to compare a an analysis of death certificates, and, unless rate found in 344 cases with the rate for Merewether's study was incomplete, these the general population without respect to cases should have been included in his re age, occupation, and many other variables, port. Of the remaining 80, it is quite pos such as smoking habits, is obvious. sible that the 31 contributed by Merewether Lynch,10 who with Smith** had reported the first case in 1935, reported 4 cases of carcinoma of the lung in a series of 49 and the 17 by Gloyne contain some duplica tion with each other or with those of other English authors. autopsies on workers in an asbestos manu facturing plant who were shown to have "demonstrable deposits of asbestos in the Principles of the Epidemiological Method luagsT This, of course, is not necessarily identical with the disease asbestosis. Lynch, himself, points out that, although this is an incidence of 8.2%, "both figures are too small for very serious statistical types of calculation." Nevertheless, later writers have used this paper to strengthen the case for an association of carcinoma of the lung with asbestosis. It is also of interest that Klotz a found only the same number of cases of lung cancer in a series nearly 10 times as large, i. e., 4 in 478 cases of asbestosis. Dorn 30 has pointed out that much of what is now 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 records, supplemented to some 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 by the same methods that have proved so successful previously in Behrens, as cited by Merewether,7* esti the study of communicable diseases, that is mated that, of 309 cases of asbestosis in the to say, by epidemiological methods. literature, 44 showed associated cancer of the lung--giving an incidence of 14.2%. This, is- an Illustration of generalizing an incidence obtained in a group of cases which were undoubtedly reported only be cause some of them showed lung cancer, to possibly hundreds of asbestotics whose cases were never reported. The same ap plies to the conclusion of Teleky,8-' who appears to have reviewed reports of 39 autopsies on persons with asbestosis among which 6 cases of lung cancer occurred. In formation from sources such as these does not justify generalizations with regard to mortality rates. Perhaps no one has written so exten In order to apply this method of investi gation to the problem- under discussionr, vr were of the opinion that a study should be planned so as to provide (1) a well-defined population group; f 23 available data for all members of this population, including the healthy as well as the ill; (3) a sample which is truly representative of the popula tion; (4) reliable and valid observations relating to the problem of the study. A serious defect, common to most of the studies which have been reported, is that little or no information concerning the healthy people in the group seems to have been available to the author. In order to draw a generalization regarding all asbestos sively on the subject as has Hueper.611* workers, it is necessary for a study to in In 1955 he reviewed the cases ** reported clude living persons as well as the dead. B rflwn--Trunn f,.V /-V A. M. A. ARCHIVES Of INDUSTRIAL Ht-.Al TH Limiting the investigation to cases coming to autopsy, as has been frequently done in earlier studies, still further restricts its use in generalization. The problem with which we are concerned is whether asbestos miners experience more lung cancer than does the general population. The answer necessitates the collection of reliable infor mation on asbestos miners as a group, as well as on the general population. It seems advisable to discuss the differ ences between the epidemiological approach and that used in the studies which have been reported to date. A very important consideration is the fact that lung cancer, in spite of its increasing numbers, is still a disease of low incidence; that is, in a given population not many persons will contract this particular disease. This fact requires that large samples or groups must be 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 (1) compar ing the relative frequency of cancer in vari ous sites; (2) comparing the relative frequency of cancer in a group of hospital ized patients: (3) comparing the relative frequency of cancer in a group of cases coming to autopsv. Attempting to compare two population groups looking only at the relative fre quency of cancer m various bodv sues, may result in finding a higher percentage ' rv.titnc t -enuenev i in one of the groups, v- hen r. : a -:. t'w mortality rate of cancer of a particular organ is exactlv the same in both groups This is very clearlv dem onstrated in the excellent article by 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 autopsy cases may not be in any way representative of a larger group, and that in dealing with such samples, the observer may easily find more cases of a given disease than would be found in another group of the same size, but representative of the general population. 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. It is the obligation of both the investigator and of those who read his report to make proper comparisons and to draw only those conclusions which are valid and justified. A good statistical study of cases of cancer of the lung occur ring in a group of autopsies can lead to a proper inference concerning the frequency of lung cancer among cases coming to autopsy, but only to such cases. For in formation. Lroro- suck * study to- be pro jected to some larger group, it is necessary that the autopsies represent a good sample 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 rq>orted by some authors may be miscon strued as applying to asbestos workers or even asbestos miners, when, in fact, the authors in question do not make this gen eralization, nor car. the generalization be made for the reasons stated. Close study of the reports reveals that the percentages cited relate only lo the group of autopsies covered bv the particular investigation. The present study, in contrast to the earlier works, has been planned, to uuIlzc the epidemiological method A well-defined group of asl>estos miners has been estab lished in such a wav that it constitutes a g> iod -ample ot the whole population of asbestos miners in Quebec. Data lor ali members of this group have been collected and analyzed. Those concerning lung can cer have received most careful considera tion. Details of the methods employed " ill be set forth later, but the tvpe of approach is considered to pe*rmit of fair comparisons and valid generalizations. Collection and Analysis of Data A preliminary survey of potential sources of information in February, 1956, involved 638 Vol 17. lure. 19SX /W -T ofo /.r.\<; < /./? / s' -ts///.v7'ov m/xi.ks discussions with the physicians in charge of the asbestos companies' proprams anil with clinicians, pathologists, representatives of Citv and Provincial health de|iannieiits and of the Canadian Cancer Society, and other interested persons. It was found that morbidity data, although somewhat limited, were available from such sources as the hospitals in Montreal and Quebec City, and the 13 cancer detection centers in the Prov ince. However, because of the high mor tality in lung cancer, it seemed advisable to depend u|>ou data relating to deaths. These vee found to l>e obtainable at the < iud. statistic? department of the M'inicrn: of Health in Quebec City. From the pre liminary survey, it was apparent that exten sive and detailed information could be gathered with respect to both the persons employed in the asbestos mining industry and the mortality figures for the general |>opulation. Following this exploratory survey, the initial effort was directed to the collection of data relating to all workers who had l>een proceed through the clinic at Theiford Mines since its inception in 1947. and similar information regarding all workers at Asbestos, Quc. Data from the clinical records included the age. familv and per sonal medical histories smoking habits, 'amber of rears of cx.|it'iire." art estimate of weighted exposure, and the course of the individual's health ~t.atlis nr the can-c of his de.vh From iht- i a: ormat ion it wa- pnv-ible to tormulatc a "cohort" which could l>e well defined, should be representative of the whole group, and could be followed for a definite period of time. All of the available experience indicates that the development of asbestosis in less than five years of ex posure must be somewhat rare. Accord ingly, the cohort was defined as including every miner who had a total exjvnsure of five or more years, and vvho was on the employment rolls in 1950. Office and other nonexposed personnel, regardless of length of employment, were not included. This cohort was then Pillowed 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 period, 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 had left employ ment through retirement or resignation. F.ventuallv, 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 tn the department of vital statistics of the Provincial HeaJth Ministry, together with statistical sum maries of the causes of deaths in the Prov ince by counties All cases in which death ivtrs certified as having been due to pri mary cancer n; the lung were examined for 'uch in formal ion as place of residence, occupation date of death hospes.' m which death occurred and whether or not an autopsy was performed. Cases in which lung cancer was given as a cause of death, but in which it was not 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 study. The statistics for the Province of Quebec relate to population, total deaths from all causes, total deaths from cancer of all types, and deaths from lung cancer. These were collected and tabulated by counties and by sex for the years 1950 to 1955, inclusive. B raun--Truoi 639 /*/ & `Y'=* F a m. a a kc I urns vi ixdlstrial hlauii From them, death rates tor 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 gTOup policy of life insur ance which, fortunately, nearly all of them 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 records on this group, the records of the life insurance company were examined for all death claims paid under the policy, and particular notice was taken of the claims in 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 company records. "r'he deaths were then verified individually oy reviewing them with the physicians in charge of the medical sendees. In this man ner, there was established a list of cases in which primary cancer of the lung is con sidered to have been proved as the cause of death A few cases in which lung cancer is strongly suspected but not proved as the cause o: death were considered separately. Mortality rates have been calculated using both the "proved" and the total of "provedand "suspected" cases during the wars 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 asbestosis, 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 be discussed separ ately from those included in the population and time-interval under study. A comparison of lung cancer mortality in the asbestos-producing counties has been made with that in counties which are far removed from the asbestos mines and in which, presumably, no asbestos miners live. Finally, in order to broaden the compari son of death rates in different population groups, the- rates- have- beerr- collected---for Canada generally, and for the United States, according to the most recent published and unpublished material. Results and Interpretation The cohort which was constructed accord ing to the criteria described in the preceding section has been considered individually and compared with the general population. Description of the cohort will be presented here as a preface to the results of the study : Original Cohort [urtt Persons Deducted Final Cohort f.ivinc n 19SS (worLm^ and retired) Head by 1955 Cancer of lunt Q>ue*i*on.dWe cancer m Iihil* t Mker causev . l nknnwn reuses, 'sniokcr< N un>noWcr\ [ 'nkuo* tt 6.Ml I3J S.958 $,771 187 9 2 ',696 *.673 1,26$ :o Tables !. 2. 2. and 4 present age. number of wars of emplovment. wetgh'ed average exposure, and smoking habits of 'he 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 ex|>osure based on a weighted average of the years s]>ent at various levels of dustiness. The degree of dustiness for each job category was determined after consulta tion with persons familiar with the environ ment and conditions in the various work I'oi IT, yum-. JV5X /*-V Ll'XG CASCEH JS ASfthSTOb MISERS TaJL 1--Sumber and Percentage Dutr \ button by Age Table 2.--Sunibcr and Percentage Distribution by i Length of Employment Ace 30-44............................................... ............ 44-6A.......................................... ............ 6A-6C............................................. ............ 64+................. ........... ............. ............ Avtnct ........... ............. ................... ............ Number 3.W! 1.134 6)5 114 3 4,954 4) * Lees (Itu 0-5%. Per Cent to ik 50 4 -- 500 Length of Employment 5-6 ............................................................ . 10-19.......................................................... . -.............. ............................................ . 90-39........................................................... . 40-4k............................................................ . 60+............................................................. . Touts........................................ . Avm you* ot employment_____ . Number 1.795 139* 972 tea 1*5 44 4.644 11 Per Cent 90 4106 to1 I too areas. For the purposes of caJculation, the assumption has been made that the relation ship between these categories is linear, and that Category II is twice as dusty, and Category HI three times as dusty as Cate gory I. uaJly 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 5 presents the year-by-year ex perience of the cohort and indicates the Table J ---Number and Percentage Distribution by Exposure Category TaJSLE 4.--Number and Percentage Distribution by Smoking Habits Eipoeure Category l.................. ...................................... .. II..................... ......................................... MI..................... ......................................... Uakpowri......... ......................................... Touts.......................................... A rente Esposure.................................. Number 2.03) 2.150 I.T72 5 S.MS 2.0 * Less thsn O.J70. Per Ceot 34 36 30 100 Smoking Babiu 6oxiken..................................... ............... Noturnovers.............................. ............... ............... Tot*!*........................ . ............... Number 4,673 1.364 20 4.644 ` Leu thsn or%. Per Cent 79 21 100 The fourth variable, smoking habits, was similarly tabulated and is shown in Table 4. This was included because the informa tion was available and because smoking was regarded as one of the variables which, besides the environment, could conceivably influence the development of lung cancer.. As used in tnis presentation, the term smoker reie's to a cigarette smoker, habit- number of deaths each year from specified causes. In general, a case was considered to be "proved" as one of primary cancer of the lung when the records showed that the diagnosis had been supported bv an autopsv or surgical resection of the lung wuh. microscopic- examrtiraricm of the re moved tissue. In one case so considered, however, diagnosis was confirmed by bron- Tabll 5--Vca^-hy } car experience iCni.'rt ana Death Rates per 100000 Man-Years cf Risk Ceuse of Death 't ear No. Alv At Bectanioc of 5 ear Proved Primary C*. of Lung Suspected Primary C. of Lunt Olher Causes 1950.............................. . 1951............................. .... 1952 ............................. 1953............................... .... 1954............................... .... 1956................... 5.9to 5.942 3.446 4.448 1 3 Q 2 1 3 2 12 0 i: 0r 1 34 0 33 0 36 Touts........... "Proved*' rate per 100,000 oin-vcan of risk - 9 9 2$.5 3 1W Unknown 1 1 0 0 4 0 6 Men-Veen ot Risk 4.050 4.932 4.903.5 5,6666 4.829 4.790.4 16.271.4 'Tour' ratt per 100,000 man-years o( risk - jj'g-'j""* 34.0 Braun --Truan o A M. A ARCH II 'Eh OP 1XDUSTR1AL HEALTH Table 6.--"Proved" Cojcj of Primary Cancer of the Lung Cue So. I 2 l 4 5 6 7 8 9 A*e 06 65 U W 4| 61 * 37 68 Smoker Vu Yu Yu Yu Y'es Yu Ym Yes Yes Exposure 36 JT. lo C*i. It 34 >7. IQ Cel. I 37 yr. in Cu. 1 33 yr. Uj Ci. I 23 yt. in C*i. II 33 yr. in Cu. Ill 30 jt. in Cu. 11 10 }T. in Cat. 1 38 yr. In Cat. Ill Died 10*12-51 V- 3-Si 7-20-Si 8-20-30 -51 4-30-A3 11-72-53 8- 5-54 3- -65 Autopsy Yes Yu No Yes Yes Yes Yes Yu Brooch. Mbeiiotts Yu So No No Yes Yes Yes No No choscopy with visualization and biopsy. In another, although there was no autopsy, the diagnosis of primary cancer of the lung seems to have been beyond question. The term "suspected" primary cancer of the lung was applied to those cases in which, the diagnosis' remains^ irr doubt* but' some of the evidence points to cancer of the lung. There were three such cases. The term "man-years of risk" has been used to mean the number of men at risk for the year under observation. A person who lived throughout the year was counted as a full man-year of risk, but.one who died during the year was counted as one-half a man-year. Deaths occurring in the cohort, and in which lung cancer is considered to have been proved as a cause, are shown in Table 6. In Table 7 are shown three deaths which have been considered as "suspected" lung cancer cases. An indication of the importance of these "suspected" cases in interpreting the results of the calculations is desirable before fur ther discussion of the mortality rates which are dented in later tables For example, it happens that the rate found for the proved cases is close to the "expected" rate based on the general population figures for the Province, as will be shown later, and on this basis we should find eight deaths from lung cancer among the cohort. Actually, nine cases were observed. If, however, the 3 additional "suspected" cases were in cluded, increasing this figure to 12, the total would be very dose to the 95% level of significance. However, having found just 12 cases, we are not above this level, and therefore the hypothesis that asbestos miners do not have a higher mortality from lung cancer than does the general population can not'be rejected. Nevertheless, the occur rence of 12 cases in this sample would increase the rate to a point which approaches the significant level. Because of the tre mendous importance of the questionable cases in this respect, some detail regarding them will be given here. In one of these cases, the suspicion of cancer of the lung is based upon the x-ray interpretation, and, although no autopsy was performed, the death certificate indicates that death was due to lung cancer. It is well known that the x-ray appearance of fibrosis, especially if a localized density or a superimposed tuberculous lesion is pres ent, can simulate that of a tumor, and by itself, does net lustifv the inclusion of this case is- nne ef "proved" cancer of the itmg A case was certified as having died bv ri.'j-oii or hydrothorax, possibly due to lung ' bin agaw. there v.a- m, surgeri and no postmortem examination. In ih* third cam . although it was subjected to autop.-v. two pathologists disagreed as to whether lung cancer was present. The death was certified as having been due to chronic myocarditis with nephritis and pulmonary congestion, and possibly cancer of the lung. On the basis of these facts, it seems unwar ranted to include these three cases among Table 7.--"Suspected" Primary Cancer of the Lung Cue No. 1 3 3 Ate 49 46 65 Smoker Ye* Ye Yes Exposure 33 yr. In Cel. Ill 33 yr. In Cu. IH 42 yr. In C*t. II Died 10-25-50 7- -53 9-30-55 Autopsy No Yes No Asbesums No Yes No Vo! 17, June. )95S f 0 U XC CAXC1.R IX . /.S"fl/: V7"Os' MIXI.RS "proved" instances of lung cancer. On the (iiher hand, they cannot, in fairness, be dis regarded completely. It is for this reason that mortality rates have been calculated Kith ways. Table 8 fives the rates by age groups. The rates by length of employment are shown m Table 9. During the first 40 years of employment, the rate rises, an observa tion which seems 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- yearsr or about- l44G-manyears~ of exposure. When the "susi^led" cases are added, one case does show up in this T.sm.E 8.--Lung Cancer Deaths by Age Croups Table */--Lung Cancer Deaths by Length of Employment Number of Person s anti Number of Lung Cancer Death- I*nnh of Employment 5-9................................ . 10-19................................ . 20-79................................ . 30-.19........ ....................... . 4(1-49................ 40+............................ Persons 1.7V5 2.308 922 603 185 55 No. of Deaths Proved Tout! 00 11 32 57 01 00 Tuuli ... 5.95b 9 12 Annual Lunc Cancer Death Rates per 100.000 M an Year* of Exposure Lanxth of Employment Prorod Tuial 5-*-..-:.......................... 10-19............................... 30-29................................. 30-39................................. 0-49................................. 50+ ................................ 0a 7 M 54 138 m 0 90 00 Orer-all.......... 25 34 Number of Persons And Number of Lung Cancer Deaths Age Group " No. of Persons No.nffM*ihs Prm*l Total 20--44 ............... .. . .. 4V54....................... . vi-M..................... -Sri-......................... . t nknown. . .. Totals__ .. 3.901 1.124 fili 315 3 i.VSb 1 1 s i u 9 1 3 3 5 0 12 Annual Lun r Cancer Death Rair p*' Man ^ eat of E x|C5ure Age group I'rox r>l 20-44.. . . 45-54.. . 55 -4A . . . . . I klri . 1 fi W rn wn .. 4 Ml.Sl jri/i User all.. 25 100.000 Total 4 44 M| 0 34 i .ertod T hu. would prnt luce ti ra te (if 0Cj per lUD.UUU, again demonstrating the imporianctr of these quc<l! icnable. but unproved, cases to the final conclusion, l*ecause. if there were no cases in this number of men with long exposure, and if asbestos is a carcinogenic agent, it must be concluded that these 240 men have demon strated considerable resistance. This is a bio logical phenomenon which has been observed previously and is consistent wuh the theory of an intrinsic or endogenous factor in can cer. The only other explanation would be that the susceptible members of this age group had died earlier of lung cancer. Table 18. which appears later in this section, in- dicales 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 10, 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 only possible error in this interpretation couid occur if the weighted exposures were inversely related to years of employment, i * ki i ! 0 - Fur..: C anrer Deaths Cv Fzp l e.V'V'Tv Number o* Pr-sm* an,! Number cf Lung Cancc* Deatr* Exposure Category No of Persons No of Deaths -- -- -............. - -- Proved Total 1.................... II................................... Ilf.................................. Unknown...................... 2.031 2.1.'-A 1.772 3 4 3 2 0 4 4 4 0 Totals____ .. 5.95h 9 12 Annual 1. ung Cancer Dealh fLaies per 100,000 Man A ears of Exposure Exposure Category Prord Tota I................... ...................... ... U .................. ................................... til.................... ................................... Unknown......... ........................ ........... .33 23 19 0 31 37 0 Overall ................................... 25 34 H raiifl -- Trwu1 /'-V A. M. A. ARCHIVES OF INDUSTRIAL HEALTH TablT 11 --.Vum6rr of Persons m Various Weighted Exposure Categories by Length of Employment Length of Employment 5-9 10-19 2i-29 SO-39 40-49 30 + u eiehted Einruuir Categories I 11 lit rato: 490 6A3 8AJ 831 314 363 243 247 216 137 76 67 41 34 21 10 Totals 2.031 Average vear* of exposure i:s 2.130 IT.* 1,772 16.6 kiK>*n 0 1 2 1 l 0 3 29.0 Tout) 1.795 2.39* 922 603 185 55 5,958 17 J in which case the heaviest weighted ex posure (Category III) would show the shortest length of employment. Table 11, which lists the number of persons in various exposure categories by length of employ ment indicates that this error has not oc curred. In fact, the average number of years of employment for each exposure category is almost identical. Table 12, which develops the rates for smokers and nonsmokers, is most striking. It shows that not a single case of lung cancer developed among the 1265 non smokers and that all cases of lung cancer, both "proved" and "suspected," occurred in smokers. Table 12 was so striking that it was felt that funner verification was necessary. It 'V3f tXjiSlbl e that some abnorma 1 distnbunor, mav ha\e occurred, e S- the non- ~ 9LL J -- `.'ufnixrr Jjtd P ercnrtagf Distribution 5n; t '.f end .^.iTtsmokcrjr by Ag C CrOUpS .. *4 i.-M . `--.-4 A'- -- \ ntio" ;i . TOLSlS . . Aversce a;c.... .. . .. Number ?mokf' Nonsmoker it ? t11 \(4 2 224 20: 150 0 4.673 39.3 1.265 44.2 Untnovn 12 4 2 1 l 20 0.7 Table 12.--Lung Cancer DeaJh for Smokers and Nonsmokers Number of Persons and Number of Uin( Cancer Deaths % by Smoking Hahi'f No. of Detibs J'ersons Proved Total Smoker*.......................... 4.673 9 13 Nonsosokers................. ljti 0 0 Uokaowp....................... 20 0 0 ToUlS............. 5.958 9 13 Annuil Lunf Cancer Death Rues per 100.000 Min Vuri of Exposure by Smoking Habits No. of Deaths Prored Tout Smokers..................................... Nonxmokers..^................... .............. Unknown.................................. 0 43 0 0 ............... ............ 34 smokers may have included a larger percentage of young men. Consequently, ad ditional Tables, 13, 14, and 15 were con structed to show the distribution of smokers and nonsmokers by age, length of employ ment, and degree of exposure. Although there are slight differences, they do not account for the fact that all observed cases of lung cancer were in smokers. In respect to age (Table 13) the combined average age of the smokers was 4.9 years less than that of the nonsmokers. Table 14 shows that as tar as lenglh or* employment is con- TKBIT. 14--Number and Pcrccr.tooe Distribution of Smokers and Nonsmokcr/ by Lrnoth of Employment L*nth nf Enjp)o\"meni 5-9........................... 119... ...................... ?>29.. . . . 30-39.......................... *0-49...................... 50-r............................. Totals.......... A*erwe lenrth of ecDDlorcoem.......... Number Smokers Nonsmoker s 1.40 t.W.T 772 433 110 33 irr 19* i 75 22 4.673 17 0 1.265 19.3 Un Ic no n !C 4 -A 4 0 Q 20 10.0 Perreauge Distribution Aye Group Smoker Nonsmoker 20-^4..................... ........ 45-S4.................. .. . ........ i>-64.._................. . ... 95-*- .................. ........ Unknown............ 68.5 19.2 6.6 35 54.5 17.7 16.0 118 0.0 Touls... ........ lOO'Te 100 % Unknown 60.0 20.0 10.0 5.0 5.0 100 % Less then 0 05%. (V4-4 Percentage Disiirlbuiton Leneth of Employment Smoker Nonsmoker 5-9 ....................... ........ 10-19....................... 20-29...................... ........ 30-39....................... ........ 40-49....................... ........ 50+........................ ........ 30.1 154 93 2.4 0.7 29.S 13 7 is.: 13 1 S.fi 1.6 Totals... ........ 100% 100% Unknown 50 0 20 0 10 0 20.0 00 0.0 100% Vot. 17, June, 19SS LUNG CANCER IN ASBESTOS MINERS Table 15--Number and Percentage Distribution of Smokers and Nonsmokers by Exposure Category Exposure Catatory I................................. . 11................................. . IU................................. . UokXMWQ................... . Totals............ . Avano irposuso oatacory___________ . Number S lookers Nonamokers 1.353 1.6*1 1,423 4 474 432 UI 1 4.673 . 2.0 1.9 UOlkDOtt'D 4 7 9 0 X U Demography in 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 1952 through 1955. PemoUft Distribution Erpostu* Cateforr Smokers Nonamokers 1......................................... II......................................... UUnki.n...o...w...n............................................. Totals........ 33.2 36.2 0.130.5 100% 37.3 35.7 206..17 100% Unknown 90.0 35.0 04.30.0 100% cemed, the smokers had worked about 2.3 years less on the average than the non smokers. With longer exposure and greater age, one would expect the nonsmoking group to show a higher rate if lung cancer were due to asbestos. Table IS shows that the average exposure category was almost the same for the two groups. Therefore, this variable seems to be of no importance in accounting for this difference. The result of this additional analysis is that none of these factors appears to lessen the effect of Table 12. Comparison of the Cohort Experience with that of the Province of Quebec, Do minion of Canada, ana' the United States.-- In order to mane a comparison of the experience among asbestos miners with that of the general population of the Province of Quebec, statistic? were gathered, as stared earlier, in the office of the Division of 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 rate per 100,000 in these segments. It will be noted from the table that the mortality rate for the "proved" cases in the cohort is only slightly higher than the rate for the Province. When the "suspected" cases are included in the calculation, the rate for the cohort rises to 33.8 per 100,000, which is about 50% higher than the rate for the Province. This, it will be recalled from the previous dis cussion of the effect of the "suspected" cases on the results, approaches but does not exceed the significant level. One further interesting observation from Table 16 is the rather marked increase m the total number of cases for the Province between 1950 and 1955 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 1954 and 195? were thought io be more nearly representative or actual condi tions Ever. so. :s quite iikdv that the genera1 r" : s rr; stud.vd tor lung cancer with, the same diligence with which Table 16--Companion of Cohort with Province of Quebec Laof Cfcnctf Deaths Anna*! Number of -- - -- - Rate per Persotu 1930 1931 1932 1953 1954 1955 TouJ 100.000 Province 1,190.000 194 230 245 303 303 357 1,624 Cohort Tout Proead 5.VZ3 t 3 2 0 3 1 3 12 1 202 \ 39 pTortnca 1.192.000 193 219 245 300 302 354 1.612 (exrludlnf aabeatos work an) r.e 33 8 2V3 22.5 Id th PrortDce (lnrti. it has b*a assumed tU male lunc cancer deaths art for men of 204- vnn. Approximate midpoint of it* enumerated population for 1951, tod tbe estimated population lor 1(54 (Rapport, Dir. dc la D< morrepbie). iNumber iltvt \t> cohort tt betfnnlnf of 1(52. Braun--Trutm 645 / -2- `Y'Dl o A|e Group 30-M 45-54 55-64 &S+ Touts A. M. A ARCHIVES OF INDUSTRIAL HEALTH Table 17.--Lung Cancer Deaths far the Province of Quebec* populaiton 777.000 2Q2.U00 IJT.UU0 121.000 1.227,000 Number of Death* 1954 Toul Certified Toul Proved Specified Primary Toul Proved 17 13 11 9 67 36 43 29 100 31 69 32 111 U 66 29 295 130 191 99 1955 Tout Certified Specified Primary Toul 17 60 117 146 Pro rod 9 35 37 54 Tout 17 116 14 Prored 9 57 54 542 155 337 152 Af Group 20-44............................................................. 45-54............................................................. 55-44............................................................. 66-K............................................................. Over-all........................................................ Death Rates per 100,000 ISM Total Certified Specified Primary Total Proved Total Proved 23 13.2 710-- l-7 1.7 I7fi 23.7 27 J 1.4 21.3 AO'.f" ' 56.2 1J 14.4... 23.4 24.0 23J 9.7 15.4 6.0 1955 Total Certified Specified Primary Total Proved Total Proved 2.2 2SL2 05.4 122.3 J.2 17.1. 4L6 44.6 2.2 25,764.7 122.3 1.3 Iff*" 41.4 44.6 27.6 U.5 27.2 124 * Data from death oertlficaus- de laf Estimate lor population obtained by applyiac 1951 perceauces for ace croups (or males to the total population lor 1954, u given id Rapport, Div. Deoographie. . 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 those in which the diagnosis was confirmed by autopsy, surge.'}', 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 1955, 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 195S figure was higher and may have been ex ceptional. 646 This comparison, summarized in Table 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 1954 and 1955 figures for the Province. It is true that, in the case of the age group of 65 and over, the five deaths provide a figure which is almost significant at the 95$c level. How ever, it should be noted that this number includes one of the suspected but unproved cases previously, referred 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 very old is not Table !8--Comparison of the Actuai and Expected Number of Lung Cancer Deaths by Age Among Asbestos Miners At* Group province Toul Specified Pnrnarv Rate per 100.000 20-44 4S-M 35-64 6MUnknown 1.6 24.5 67.6 89 3 No. ol Miners Erpecied No ol Deaths Observed No. of Deaths Proved Toul 3.901 1.124 613 313 -3 0t 1 1 2 13 2 33 ..2 45 00 The eipected number ks booed on the ,t,rut ol the IBS) eod IS1 on-ipecifie rsiei lor the Prorinoo of Quebec, t Actiiolly 0. Vol. 17, June, MS /j nn.i, ng'^ tfr LCSC CASCER IS ASBESTOS MISERS Table 19 --Age Distribution of Adult Moles for Table 20--Annual Death Rates per 100,000 f-'r the Province of Quebec, 1951 m Cancer of the Lung in Canada Alt Oroup 20-44....................... . 48-64....................... . Si-64....................... . 66+........................ .. Toul............ Number 777.136 ISA.952 128.944 113,467 1,138,498 reirenufe 63 16 11 10 100 Terre meet in Coboa 86 10 10 5 100 Rapport, 1984. a matter of the same intensity of interest as it is in younger persons. Table 18 also answers a question pre viously raised. It snows that the members of the cohort have not died from lung can cer at an age earlier than the general popu lation. and that such an explanation cannot be offered- for the absence of lung- cancer in 240 men with more than 40 years of employment referred to on page 643. Before leaving this comparison of the Province with the miners, it should be shown that their age distributions are rea sonably the same. That this is the case can be observed from Table 19.. It should be remembered that the miners retire and consequently, it can be expected that the oldest age group will be larger in the general population. The data presented in Table 20 indicate that the lung cancer rate generally decreases after age 70. There fore. we could expect the rate for all people over 65 to be smaller than the rate for the group between 65 and 75. which would apple :o the. oldest, group of, miners, It is felt that by using the whole adult male popula tion. we ha\e developed rates for the gen eral population which are somewhat lower than, it wc had been able to exclude tnc people in the general population over 75 A comparison between the asbestos miners and the population of the Dominion as a whole was made, using statistical material from several sources. In one source, Phil lips T gave age- and sex-specific rates for Canada for three periods between 1931 and 1952. The rates for males are given in Table 20. These figures show strikingly the increase in rates between 1931 and 1952, and this Ate Oroup Urvler 30 30-34 36-39 40-44 46-49 60-64 S6-S9 60+4 66-60 70-74 78-79 80-84 IA+ All Aft* 1031*1933 0.2 0.9 2.0 3il 6.2 8.2 12.7 12..S 16.1 10.7 16.8 11.4 24 Oroup* of Yoon 1941-1943 OJ 0.9 3.2 6.4 12 6 18-9 77.0 J3.: 34.6 106 30.0 77 4 MJ 7.1 1960-1962 1.0 04 Ju 6.6 16.7 rj 69.7 77,| ICE 6*4 83.9 69.7 71.0 16.8 * '"Mortality from Lunp Ctnccr In Cunadj." 1UI 10 193?. increase is particularly marked after age 50, confirming an observation previouslymade, to the effect that until recently lung cancer has probaBTv' Been underdiagnosed in 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 Apr Group 20-i t 4 S 54 55-64 65 + Rate S 27 60 90 95 These rates are, in general, lower than thos^' developed for the toral f proved1 and' suspected I cases of lung cancer among the asbestos miners. The onlv large difference, howev er, is ir. the age group of 65 vears and over, and it is quite possible that the rate for this group may have increased for Canada between 1952 and 1954 as it did for the Province of Quebec (Table 17). A further comparison has been made with an over-all rate obtained from the American Cancer Society for respiratory cancer deaths in Canada in 1953. This rate, for males, is 20.8 per 100,000, or 5 more per 100,000 than Phillips' 1950-1952 rate, and compares with 25.3 per 100.000 for proved cases and 33.8 per 100,000 for total cases among the Braun--Trutm 647 n A. M. A. ARC HI I ES OF INDUSTRIAL HEALTH Table 21--A umber of Deaths and Death Rates f,ti 100,000 by Age Groups for the Adult Mate Population of the United States* Aft Group 30-44 46-W ii-C* Toul Population 24.544 000 .Ott.Uti 6.34fl.0u0 5.670.000 44.619,000 ClM5 1979 6.264 6.463 16.599 IUIC per 1 3.6 36.9 966 114 J 37.2 * D>u Irom "Vlul SuttstKX of tbe L'nlied Staler." Vol. I knd 2. l5i asbestos miners in this study. It is there fore obvious that there are no important differences between the rates for asbestos miners and those for the general [>opulation of Quebec and the Dominion of Canada. 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-specific 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 S. Still other rates for the United States were obtained from the American Cancer Society, and for males, these were 25.3 per 100,000 in 1953, and 28.0 per 100,000 in 1955. They are not identical with the rate calculated from the figures of the office of Vital Statistics, but this is possibly because the American Can cer"Society rares are far maics of aif ages Xevertheic?-. they. too. compare favorably with the rare; of 25 for 3J for total cases) 'btam.mc amonc rhe 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 fas distinguished from the gen eral population groups iust discused, who have no exposure) an interesting observa tion can be developed by deduction. Hueper 5* has stated that there are about 35,000 f*ersons 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 643 way, and other countries, at least 50,000 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 asbestosis with lung cancer was reported. At least 1,000,000 man-years of exposure has thus been accumulated, and this figure can be divided by the approximately 150 cases of lung cancer with asbestosis re ported during the 20-year period. This gives a rate of 15 per 100,000, which is at least indicative that any lung cancer rate which can be calculated for workers ex posed.. to- asbestos1 dust* is- not- much- greater" than that for the unexposed population. Comparison Between Eight Counties Ad jacent to the Asbestos-Producing Areas and Eight Selected Counties.--To compare lung cancer mortality rates in the counties sur rounding the asbestos-producing areas with another group of counties in which no as bestos miners are likely to reside, the rates were computed on the basis of figures for the years 1950 through 1955. The eight counties selected for comparison were Argenteuil, Chateaugay. Montmagny, Portneuf, Richlieu, Riviere-du-Loup, St. Hyacinthe. and Terrebonne, mainly because they represent a wide geographic distribu tion throughout the Province. The counties selected because of their, proximirv to the* asbestos mines include Arthabaska, Beauce Drummond. Fromenac. Megantic. Rich mond, Sherbrooke and Wolfe Table 22 shows :h; nurr.U-r o: mng cancer deaths for the years 19c0 through 1955 for each of these counties, and a mortality rate, based on the adult male population in 1952. To emphasize the comparison, Megantic County has been shown separately, as has the Province of Quebec and also the Prov ince with the eight "asbestos-producing" counties subtracted. Because of its unique lung cancer death rate, Montreal et Isle de Jesus has also been listed in order to provide further comparison. It is apparent from the table that the lung cancer death rate for the eight counties Veil. 17, June, 10SS / <=> I f Ll'XC CAS'CER IX ASBESTOS MIXERS Table 22.--Xumber of Lung Cancer Deaths and Rate per 100,000 Man-years Counties Monatle County Etbi "Adiaoctu" Counties Elfbt SeWciod Couotiei Prtmcx* o( Quebec ProTtaee of Quebec Us elfbt "edteoeot" counties Monueel it IsU de Jesus Adult Mile - Population 1032 1930 13.100 07.600 63.000 1,196.000 3 6 2 196 1,100.000 394,000 100 3 Meie Um* Center Deaths 1031 1 3 10 230 217 7 1032 3 9 3 343 ZM 136 1933 3 16 11 303 357 192 1934 I 4 3 303 290 113 1933 4 16 0 337 341 235 * It is uwiMd that all male lunj ceooer deaths occurred after ai X. Total 13 34 40 1624 1370 770 R1a0t0e.00p0er 101*4 04 22.6 233246 immediately surrounding the asbestos-pro ducing areas is practically identical with that of eight counties selected for comparison. While Megantic County has a rate nearly twice that of the combined eight selected counties, it is lower than the rate for the Proviace. arrch considerably Tower than the rate for Montreal. The figure for Montreal would certainly be higher except for the very low numbers of deaths reported for 1950 and 1951, and it would appear that in those years some error in reporting has undoubtedly been made. On the basis of the other years, 1950 and 1951 deaths would be expected to be about 200 greater. This would result in a rate 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 anv greater incidence of lung cancer than those who live elsewhere in the Province. Comment, on. All Recorded Lung-CancerCates, Lhing and Dead, amono the Asbes tos Miners --Although a simple enumera tion of al! the known or suspected ca^es of cancer of the lung in these areas has no particular value from a statistical point of view, it is 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 inves'igation, there were nine proved cases and three suspected cases in the cohort. Through 1956 and to date in 1957, there were eight deaths, six 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" but 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 years 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 III, and six worked in an exposure represented by Category I. There were only 17 among these p-ovrd lung cancer cases in which we ha\e in formation regarding the presence of asbestosis. Asbestosis "'as 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 bv asbestosis. Summary and Conclusions Interest in the question of whether there may be an association between lung cancer Braun--Truan 649 A. M. A. ARCHIVES OF INDUSTRIAL 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 fn 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 of exposure and who were in the industry in 1950. Data relative to their characteristics were collected and their status at the end of a Cx-year period of observation was de termined In the case of those who had died, an exhaustive search of death certif icates .and insurance records was earned our 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 United 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 was not possible 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 was found that 4673 were smokers within the definition of that term as used in this study. Thirty-four per cent of the cohort were more than 45 years of age, and thirty per cent had been employed for longer than Z0' years. Tfifrry per cent had a weighted exposure which placed them in the category of highest ex posure. The mortality rate for lung cancer, as computed on the basis of nine "proved" deaths among the cohort was 25.3 per 100, 000. When the three "suspected" cases 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 and because they influence the results so mark edly. 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 carcinogenicity of asbestos Comparison of the experience among the asbestos miners with that of various seg ments of the unexposed, 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 (25.3 per 100,000) compares well with the rate of 22.5 per 100.000 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 rate' 650 VoL 17, June. J9SK / 7 rf-L-0 LL'XC CAXCER IX ASBESTOS MIXERS 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 asbestosproducing areas, in which it is presumed most of the asbestos miners live, have al most identical mortality rates with those of eight counties widely scattered through the Province, and are lower than those for the 6. Behrens, W.: Experimental Asbestosis, Schweiz Zischr .dig. Path 14:275-297, 1951. 7. 'Behrens. W., Jr.: The Clinical Picture and Pathology of Asbestosis, Ztsclir. Unfallmed u. Berufskrankh 45:129-140 (June 15) 1952. 8. Berblmger, W.: Increase of Lung Cancer and Diseases Due to Dust Inhalation, Med. Klin. 27:1337-1342 (Sept. 11) 1931. 9. Berenblum, I.: Irritation and Carcinogenesis, Arch. Path 38:233-244 (Oct.) 1944. 10. Bohne: Asbestosis, Deutsche med. Wchnschr. 62:928-930 (June 5) 1936. 11. Bohme, A.: Results of Periodical Examina tions of Workers in an Asbestos Factory, Beitr. Silikose Forsch. 11:34, 1951. remainder of the Province, and much lower than the rate for Montreal. Since 1940 there have been 19 cases in which rhe,-diagncrsfs' of primary- cancer'-ofthe lung may be considered to have been proved. Approximately half of these cases were associated with asbestosis. All but one 12. Bowles, O.: Asbestos-Milling, Marketing and Fabrication, Information Circular No. 6869, U. S Department of the Interior. Bureau of Mines, 1935, pp. 1-26. 13. Breslow. L.; Hoaglin, Li; Rasmussen, G., and Abrams. H. K.: Occupations and Cigarette Smoking as Factors in Lung Cancer, Am. I. Pub. Health. 44:171-181 (Feb.) 1954. ' died in the recognized "cancer-age" and at 14. Bristol. L. 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