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X Reprinted from the A. M. A. Archives of Induct rial Health June 1958, Vol. 17, pp. 634-6S3 Copyright 195S, by American Medical Association FROM An Epidemiological Study of L a'PafstJ Lung Cancer in Asbestos Miners DANIIL C MAUN, M.O., and T. DAVID TIUAK, M.A., Ptmfcwfti Ever since the pronounced increase in the incidence of lung cancer among male* 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, Smith** 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 after the reforr of a case by Lynch and Smith** in 1935. Within the next 10 years, about 15 additional cases were re ported, ami in 1954 Merewether T* reviewed all deaths from asbestosis recorded in Eng land since March, 1924. Lung cancer oc curred in 16% of these cases. Gloyne,41 Accepted for publication Jan. 20, 1958. This study H-a< made possible through a grant from the Quebec Asbestos Mining Association. Medical Director (Dr. Tlraun) and Statistical Consultant (Mr. Truan), Industrial Hygiene Fondation whose work is also frequently re, as establishing a connection between asbes tosis and cancer of the lung, reported in 1951 that cancer of the lung was present in 14.19b of asbestosis cases examined by him. In 1941, Nordmann and Sorgen 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 1^5 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 * in 1939 reported that he had discovered no 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 canerr was ino small for statistical evalua tion. In 1947, Wegelius** reported 126 radiologiailly diagnosed cases of asbestosis among 476 workers in Finland, and found no cases of lung cancer in this group. Goldbiatt and Goidblatt in their section of Merewether's latest book,44 state: "But at no stage in all these impressive researches was any due obtained which might have offered any supjwrt to the possibility that asbestos could act as a cardnogen. There 634 ' /r/* l.f.\G CAS'CT.R JK ASMiSTOS HIKERS is no reliable criterion by which one rais .uinci|Mte carcinogenicity ami. 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 decuni|suiun product of it can be obtained, asbestos might be considered as a "co-car cinogen" which only induces a further de velopment of a preneoplastic condition brought about by something independent of the 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 and generalized beyond the $co) of the works which they quote. Nowhere, for example, have we found references to a refutation cl asbestos workers, although several authors who have quoted the ob served incidence of lung cancer tit autopsies of persons iuho also had asbestosis 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 cime to autopsy. With the exception of a pa|cr by Doll,** none of those reviewed gave any data on cx|>osurc 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, funhennurc, 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 radiologically detectable condition. Most of the published reports obviously included women among their rases, but some of them do not give the number or proportion 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 Huqxsr ** in 1953, only 10 appear to have originated in the United States, and 7 in Canada. Some of the earlier reports apparently 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 history of cancer, length of time in the industry, and age of the individual case are also notably absent in the majority of these reports. With thi- understanding of the limita: mu- #:' :hc existing literature with respect io epidemiological generalization, it may be .it value to consider in somewhat more de tail ome representative earlier publications, a few of which were referred to briefly above One of the most derailed studies and one which deserves the most serious considera tion is that reported by Doll** in 1955. This study reviews causes of death among asbestos workers based on coroners' rec inK. It alvi attempts to estimate the risk lv studying records of men who worked for at least 20 years in exposed situations. Broun--Tntan /V 635 O A M A AHUtn l..s Ol l.\ HI 'iTNIAl. HI.AI.Tll Dull concluded '.hat iung cancer was a spe cific industrial hazard of certain asbestos workers and that, after 20 years of expo sure. the risk is 10 times a* 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 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 2t) 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 flung cancerl may be a hazard i in asbestos workers) has been produced h\ Merewether and by Glovne " In 1951 Gioyne<l presented a review of 1205 autopsies on persons who hail 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 vya- 6.7%. and in 169 cases which proved not to have any type of pneumo coniosis it was 8.39c- 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. Gloyne'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 {loints out that the rate 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 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 it really shows is the fact that in a group of 121 cti'-e'. selected for special studv pri marily licciiu-r they seemed abnormal bv preliminary examination. 17. or I4.IG. had lung cancer Mercwclhc- ' m 1C|47. i:i thi n-;mri of the t_: * !:*;...tut i,: r-.ictunes. rc\ tewed all caw> rc|irted between 1924 anil 1946 in which asbestosis was the cause of death or a coexisting condition. This work was later extended to include all such cases re|iortcd up to l^eccmber, 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. It is quite possible that a large number of asbestotics who did not die of their asbestosis. or in whose 6J6 I'ol 17, Jumr. JP.tf 4. I.VSG CASCT.R IS ASBESTOS MISERS death certificate it was not mentioned, may prior to that date and enumerated a total have been missed. The import of this \b% ' 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 oncer in autop covered by other authors. Eight were dis sies of the general imputation 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 Tate 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," 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 lungs." 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 w 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 * 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," 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 14.25. This is an illustration of generalizing an In order to apply this method of investi gation to the problem under discussion, we were of the opinion that a study should be incidence obtained in a group of cases which were undoubtedly reported only be cause some of them showed lung cancer, to planned so as to provide (1) a well-defined population group: <2) available data for all members of this population, including the possibly hundreds of asbestotics whose healthy as well as the ill; (3) a sample cases were never reported. The same ap which is truly representative of the popula plies to the conclusion of Teleky,** who tion; (4) reliable and valid observations appears to have reviewed reports of 39 relating to the problem of the study. 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. 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 Perhaps no one has written so exten draw a generalization regarding all asbestos sively on the subject as has Hueper.114* workers, it is necessary for a study to in In 1955 he reviewed the cases * reported clude living persons as well as the dead. Braum--Tman A.V /-V , A. M. A. ARCHIVES Oh 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 berween 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; f3) comparing the relative frequency of cancer in a group of cases coming to autopsy. Attempting to compare two fiopulation groups, looking only a: the relative frequenev of cancer in various body sites, may resui: m finding a higher percentage T'eouencvi in one of the groups. Ah--* f. :vrt, the o.mrroiify rate of cancer of a particular organ is exactly the same in both groups This is very clearly dem onstrated in the excellent article by Dorn.*0 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 from such a study to be pro jected to some larger gToup, 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 rqwrted 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 can the generalization be made for the reasons stated. Close study of the reports reveals that the percentages cited relate only to the group of autopsies covered by the particular investigation. The present study, in contrast to the earlier works, has been planned to utilize the epidemiological method A well-defined group of asliestos miners has been estab lished in such a way that it constitutes a good 'ample of the whole population oi asbestos miners in Quebec. Data for all members of this group have been collected anti analyzed. Those concerning lung can cer have received most careful considera tion. Details of the methods employed will be set forth later, but the type of approach is considered to permit of fair comparisons and valid generalizations. Collection and Analysis of Data A preliminary survey of potential sources of information in February, 1956, involved 636 VoI 17. Jour. I9.V /W /./'At, t'.-l\( I.B IX .4SHI.\Tt>S MIXI.Ks di>aiaaioris with the physician* ill charge of the asbestos companies' program* and with clinicians. pathologists, representatives of City and Provincial health de|>anmriii* and of the Canadian Cancer Society, and other interested ]txis. Jt was found lhal morbidity data, although somewhat limited, were available from such sources as the hos|)itals iu 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 ui>on data relating to deaths. These \ve found to l>c obtainable at the vital statistics deiwrtmcui of the Mutism ttf 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 |>ersnns employed in the asbestos mining industry and the mortality figures for the general population. Following this exploratory survey ihe initial effort was directed to the collection of data relating to all workers who had leen proce-sed through the clinic at Thetford Mines since its inception in 1947. and similar information regarding all workers at Asbestos. Que. Data from the clinical records included the age. family and ]>ersonal medical histories smoking hahits. number of years of exposure, an estimate of weighted exposure, and the course of the individual's health status nr the cause of his devh From thi- information it wa- |m*siblc to formulate a "cohort" which could 1< 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 ex|v>sure ot five or more years, and who was on the employment rolls in 1950. Office and other nonexposed personnel, regardless of length of employment, were not included. This 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 period, reference was made to the physial examination results and x-ray findings at the end of the jieriod. 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. Kventually. all but a small number of these were accounted for as either living or dead, ;uul in the latter event, the cause of death was substantiated in a similar manner, and the result* 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 a? having been due to pri mary cancer of the lung were examined for -uch information as place of residence, occupation da:>- of death hnp:;;..' " which death occurred and whether or not an autopsy was jierformed. 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 lo population, total deaths from all causes, total deaths from cancer of ail types, and deaths from lung cancer. These were collected and tabulated by counties and by sex for the years 1950 to 1955, inclusive. Broun--Truan 639 /*/ 6 7^ * a m a AKCiuri.s ur isdlstrial HLA/.ru From them, death rates for 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 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, "''he deaths were then verified individually oy 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 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 "proved" and "su-pected" cases during the wars un der observation. Comparisons were then made between the death rates from the same cause among specific segments of unex;iosd persons. All lung cancer deaths, both suspected and proved, were carefully ana lyzed to determine possible relationship or correlations between the develo|mcnt 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 10 (his 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 been collected for Canada generally, and for the Un'ted 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 Lott Person* iMluctcii Final Cohort Ijeni* in 1955 4iw| rriirnl) 1 v*d by 1955 Cantor of lunt lOtuMe cancer 'mk- Oftier ciuftet l nknnmn 'MinAtr* Nansiiioker) (*nkitoii 6.091 in $.958 $.771 is; 9 j 169 6 4.673 1.265 :o Tables 1, 2. .1 .iiib - r'ren; age. number oi vears of employment wvgh ed average cx)>osurf, and 'inokmg habits of 'he cohort. A com|iariM)n of the exposure to asbestos dust is presented m Table 3. All members of the cohort were placed in one of three categories, represent mg 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 l';l. //, Jim,-. JV5* f-3-/ ? 7^-0 LUNG CANCER IS ASRhSTOb MISERS TaSLC 1 --S'umber and Percentage Distribution TaJLX 2.--Number and Percentage Distribution by by Age Length of Employment AC 30*44.................................... O-H..................................... 39-H..................................... 63+ ...................................... .......... Numbtr 3.W 319 .......... 3.93ft Per Cull Aft IV 10 3 too * Lxm tlias 0.3%. Land!) at Employment 3-0....................................... 10-19................. ..................... 30-39............ .......................... 10-91.................................... 40HH............ ......................... *0+........................................ Totals.......................... Anm nmiwpiortDL.... Norntar 1 fU 13M B 1A& i.*S 10 Far Cam 40 14 130 1 100 areas. For the purposes of calculation, the assumption has been made that the relation ship between these categories is linear, and that Category II is twice as dusty, and Category III three times as dusty 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 S presents the year-by-year ex perience of the cohort and indicates the Table 3.--Number and Percentage Distribution by Exposure Category Tabu: 4--Number and Percentage Distribution by Smoking Habits Eidhun Cauory nl..................................................................... Ill....................................... Ubxdovti............................. Touts...................... ............ A rant* Esposurt........................... NiimHar 1031 IBM J.0 ' Lea then 0.3%. rar Cast 34 3ft 30 100 Smokiot Habits Staokan........ ................ Noutsokan........ ......... Unknown..................... * Vtu Mao 0J%. 1 i Noubar CS7J 1BU 30 10M Par Cast 7$ 21 m 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 innuence the development of lung cancer. As used in this presentation, the term smoke- refe'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 by an autopsv or surgical resection of the lung with microscopic examination of the re moved tissue. In one case so considered, however, diagnosis was confirmed by bron- Tasle 5--Ycar-b\-Ycor Experience <.; Cnhert and Death Rates per 100.000 Mon-Years of Pise Cmwot DotB Ymf No. Alirr At Bacmniac ar Vaar P*ad Primary Ca. ot Luns SuiDKtad Primary Ca. of Lun| Outer Causal 1030......................... 1911.......................... ....................... 1033......................... 1934......................... 1933......................... Touts......... 3.0* 3.043 3.IBS 3.MS 3.110 1 3 0 9 1 3 3 13 0 17 0r 1 34 0u 0 3mfbt 3 109 "Provad" nu par 100.000 min on of ran- -- 23.3 Unknown 1 1 0 0 4 m0m ft Man-Vasn s< Risk 3.030 9.033 9.900.3 iJOft-1 3J39 M3,7U90M.3 js.rrt.s Tsui" iw per 100.000 nun-yurt ot rat jjjffj-1" *** Broun-- Truan /* o Cue So l 2 3 4 4 6 7 $ 9 A St A ARCHIVE.1 OF INDUSTRIAL HEALTH Tabu 6--"Proird" Cases of Primary Cancer of the Lung Aft Smoker 06 Yu 63 Yu 63 Yu 99 Yu a Yu 61 Yu M Yu 37 Yu U Yn Cipotura M n. In Cu. It M yr. in Cu. I 37 yr- u Cu. 1 31 yr- m Ctt. 1 Syr-la Cu. It 33 yr. in Cu. Ill 30 yr. in Cu. It 10 yr. is Cu. I 3t yr. is Cu. Ill DmO 10-13*31 6- 3*36 7-30-43 6-30-30 -31 00*33 11*22*33 6- 3-44 >- -66 Autopsy Yu Yu No Yu Yn Yu Yu Yu Brooch. Astitsiosu Yu No No No Yts Yos Yti No No choscopv 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 in 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 discu"on of the mortality rates which ?re derr. rd m later tables For example, it happen- 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 close to the 959c 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 nut iutify the inclusion of thi< case a< nnc of "proved" cancer of the ituig A -r.'.iu! ca*e was certified a having died h\ oja-on <>: hydrothorax. po'sibly due li< lum; > ' blit acnir. the'e wa- no surgerj .md nc postmortem examination. In th** third c.i'i.. although it was subjected to autop>y. 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 Ta*iz 7.--"Suspected" Primary Cancer of the Lung Con No. 1 3 3 Aft 4494 43 Snokor YYdu Yu tiyoum 1332 yyrr.. lion CCoott.. lIiltl <3 yr. to Cu. II DW4 10-24-40 97-*30^-6433 Autopsy No NYots tibituaa No Yu No 642 Pol 17, June. 195t I.l At, C.IXCI.R IX .-/.VW/:'STDS Ml.M RS "proved" instance:. of lung cancer. On the other hand, they cannot, in fatrnc.ss, be dis regarded completely. It is for this reason that mortality rales have been calculated Itoih 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 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 years, or about 1440 man-years of exposure. When the "susiiected" cases are added, one case does show' up in this T.s nee 8.--Lung Canter Death* by Age Groupt 1 able ') --Luno Cancer Deaths by Length "J Employment Number of Perwm*. aui Number of Lung Cancer Death* of tmiikoymetu No of I'orsoos No. of Death* i Framed Total 150--10$.............................................. 2l.TJVMS 30-39.......................... 9B .................................... 403 40-49......... ........ 404*..................... 55 0I 3 5 o 0 0I 1 T i 0 Touts ... 55.9.9550b 9 13 Annual Ung Cancer Death Rates per 100.000 M an N ears of Exposure Loneth of Emptoymeni Froeil Tull! 5-9........................ ..................... 10-19......................... 90-39.......................... 30-39........................ 40-*9.................................................. 40+ ......................... ....................... 0 0 0 o 54 193 90 0 OTortoli............................... 35 34 Numhrr of Persons and Number of I-un (asm Deaths Age Ufvui> * Vo. of imm No. nt [MUM l*mved Total 30-M................. VSS..................... *4-04................................... 1 nknown . .. J.90I 1.194 MS 315 3 1 i i 4 u l i 3 & 0 Touts.... 4.95a a 13 Annual l.unr Cancer Death Rate* per 100.000 .Man Years of Etioture Age group Ito'iM Total -44................. 45-54... 45*4M............... r*s+ . . I'nlsnown.. ........ 44 IS 44 Al At 313 3A5 ii 0 (Jicr-ull.. 2: 34 i.eriod Tni would produce a ra tc of 6 per lOO.UiJO, again demonstrating the imlonance of these questionable, but un proved, cases to the final conclusion, liecaus-.*. 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 inen have demon strated considerable resistance. This is a bio logical phenomenon which has been observed previously and 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 this age group had died earlier of lung cancer. Table 1R. which appears later in this ection, in- Hmun--Truan 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 10, and it will be noted that they present strong evidence against asbestos taring 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 oniv possible error in this interpretation could occur if the weighted exposures were inversely related to years of employment, Tki !0 - l.unr t'nnf,-r Deaths by Exposure Ca:ei.<ry Number o* P-an! Number : Lung Cancer Dear F.tnosure Category \n of 1`croons No of Donths Prouort Total 1................ tl............................ til.......................... Unknown.................. 3.031 2.1* i.m 5 4 3 3 0 4 4 4 0 Touli........... 3.95a 9 13 Annual lung Cancer Death Rates per 100.000 Man Years of Exposure F.iOfttuft Coittorr Protod Too f .................................... It .................................... in..................................... .......... Unkaowti............................. 19 u 31 3f;t 0tor-oil................... .......... 35 34 643 /'-V A M. A ARCHIVES OF INDUSTRIAL HEALTH Table 11 --X umber of Persons m Ko riant Weighted Exposure Categories by Length of Employment " cientod Eipneur* Caieeorm lantih or -- ------ Eaptorment t u lit S-f 10-10 *-a 30-30 40-10 SO 4- TOT 40$ 400 A3 m $41 114 Ml 242 247 2ia ii: 76 67 41 a 91 10 ToUlS IMI Aormc< Mtr* of ipotttf* 174 2.140 IM I.JTJ IM Unknoo'n 0 1 2 1 t 0 4 204 Toul 1.704 2.20$ m 603 164 44 4.05$ 17J 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 nonsmokers 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 'as oorsibie that some abnormal distribu tion mat' ha\e occurred, e. g.. the non- T.sle o--.Vumi>rr and Percentage Distribution 5:-er~r ana Xonsmokers by Age Croups * :* '> *V; r .* '41 4 ! W4 t r.tno^n . .. .. T oiali.......... a;c................ Vuabtr Smokr* 3 W 411 |{<4 2 Nontmofce? Mt 224 203 1400 4473 1.265 44 J Unrnowr 12 4 2 l l 40.7 Table 12--Lung Cancer Death for Smokers and Nonsmokers Number of Persont end Number of Lun( Conccr Death, by Smoking Hibitt No ol Dootbs I'onons Provo# Total Smokers............... Nonasokon.......... Udkdo.q.............. 4.073 1.365 20 00t 102 0 Totals........ 5.$5I $ 12 Annual Lunf Cancer Death Haiti tor 100.000 f L*notore by Smoking Habm Man.Yean No. o( DooDn Prorod Tool SNmoooakmono.k.a..n........................... (inlnm................ 32 43 00 0 0 Ooer-oll......... 34 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 far as length of employment is con- Table la--Number and Percentage Distribution of Smokers and Nonsmokers by Length of Employment length nf Emslormem 5-0..................... l*M6......... 30-20.................... 30-35..................... 40-49................, 40-4-....................... Totals........ AWUI Itutb or captortnom........ Nurotar Smokers VontrooLtri 1.40 3TT 1.967 43h 722 433 14a no 33 m?m\ 4.$n 1.264 j:.o Unknown 1C 4 4 0 0 30 lfi.0 Ptrrvauf* Distribution Ate Group Smoktr Nownoktr 20~M.................................... 44-M........................... S3-*........................... *4+ ........................ Unknown.................. M-5 19.2 14 3.5 * 44 ^ 17.7 160 114 0.0 Totals........... 100% 100% Unknown MO 200 tO.O 5.0 54 100% * Lm than 0 05%. (U4 PorvtMOft Distribution Loneih of Enpbjrawm Smoker Xontmokor 4-6....................... 10-19....................... 20-29....................... 30-39....................... 40-4$....................... 50+........................ 13.4 a* 0.7 29.6 33 7 13.7 13.1 4.9 1J Totals........ 100% 100% Unknown 40.0 30.0 10.0 200 00 0.0 100% Vot. IT. June. I95S Sjy LUNG CANCER IN ASBESTOS MINERS Table 13--Number and Percentage Distribution of Smokers and Nonsmokers by Exposure Category Emotur* Cuetorr t..................... II........................... UIalflc.D...o..w...Q.............................. Totals....... mutortyrp..o..f.l.u..n.... Number Sotoksn Konsmektn 1l.4M11I 1.43ft 474 m4ft3 41 4.(73 1J0S 3.0 14 Uokaowp 4* 9 0 .0 90 U Ptmsaiac Datrtbottoo Emotur. Coioiorr Smoktri Nonssok.n III............................ ...... CIoUc.a.o..w..o.............. ...... 33.3 0.1 r34a.7 a0..?1 Totali........ 100% 190% Uakpown 30300f.t.0040 100% cemed, the smokers had worked about 2.3 years less on the average than the nonsmokers. With longer exposure and greater age, one would expea the nonsmoking group to show a higher rate if lung cancer were due to asbestos. Table 15 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 or the Cohort Experience with that of the Province of Quebec, Do minion of Canada, and the United States.-- In order to make a comparison of the experience among asbestos miners with that of the general population of the Province of Quebec, statistics were gathered, as stated earlier, in the office of the Division of 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. 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 annua! 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 effea 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 in the total number of cases for the Province between 1950 and 1955. It is assumed that at least pan of this increase is due to im proved recognition and reporting of iung cancer during the interval For this reason, the years 1954 and 1955 were thought to be more n-am representative of actual condi tions F.' ; 'puite likes that the ger.er.,1 ; r.'-; i.e-j for iung cancer n -r the same diligence with which ftottnm Cobon Total Rioted Rtomte. lotrludlac asbasiaa TaUX 16.--Comparison of Cohort unth Province oj Quebec Laac Cuar Doatbt HfMOl IMO IUI 1993 Iftftl I0M lUft 1,101.000 III 30 M3 301 303 1ST 9.90 t 3303 1 3 1 3031 3 1,193400 m 311 34ft 103 AnnotJ Rale per Total 100.000 1.834 r4 12 1413 131 34.3 S4 la tut frortaci Sror*v it has bass usumrt all mak luas eaacar OaatM tit tor ssa el 30* *oan. Appretuaaia midpoiat ol lit. ratsowrtied populationlor 1991, aad taeoniaaiad population lor ISM (Rapport, Dir. Ot li DtlaoraphHl. (Number allot la cotton si bostnnlns of 1133. Braun--Tmem / i. i f* * Aft Croup 46-M M-64 s+ Touts A. M A ARCHIVES OF INDUSTRIAL HEALTH Taile 17--Lung Cancer Deaths for the Province of Quebec Population rrr.ooo ZS.U00 13T.UJ0 121 .(DO 1.277,000 Number of DaalJit IBM Toul CarttOad SpactAod Primary Taul Prorad Toul Prevad 17 n n 67 M 43 100 36 OB 111 u 06 -- m 120 Ul 9 SI 21 IB IIU Tout Cart)Aad SpoolAa<1 Primary Total Prarad Total Prarad 1J 9 17 9 00 16 33 117 14 67 116 M 1U 67 64 H *o UA 337 163 Aft Oroup 30+4............................... ................ 46-64................................ 6^+4..................... .......... ................. 66+................................. ................. Overall........................... DaaU Katas par 100,000 1964 Toul Certified Specified Primary Toul 2J 7X0 91.7 --re Proved 1.7 17J 27.7 27J " 9.7 Total 1.4 714 60.4 664 16.4 Prarad 14 14.4 23.4 34.0 3.0 1966 Total CoruAad Sport Aad Primary Total Prarad Toul Prarad X2 29.7 16.4 1224 amara 27.1 1.2 X2 17.3 77.1 4L6 64.7 44.6 12X3 MHO 1X6 37J 1.2 16J 41.6 44.6 mature IU * Du tram Math ormAeaur t Enuaau lor population obuinod By applylnj Mil paireaufia lor Mi fTBup> tor molts is tbo mul population tor IU4. u gists 10 Rapport. Dir. dt 1* Dtmognphit. 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 bythe 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, 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 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 1955 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 95level. 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 Taill 18--Comparison of the Actual and Expected Number of Lung Cancer Deaths by Age Among Asbestos Miners Atf Oraup Prarlnm Toul SpanAad Pnmarr Halt per 100.000 20+4 4MM 66-64 AWUoknorrn 1.S so 67.6 MJ Obarroad No. Ereread of Daatbi No. 4l No. of Mlnm Daaitn * Prerod Total 3.101 1.124 616 316 3 Ot 1 t 2 13 3 11 ..2 4 6 00 Tha alpaeod (lumbar U Bared os Ilia arormat ot tha lM aad IIU an ipaciht raiai lor tha Prorinca ot Quabac. t Actually 0.4. Vot. 17, June. 19St LLXC CASCER IS ASBESTOS MISERS Tale 19 --Apt Distribution of Abull Males for Table 20--Annual Death Rates per 100000 the Province of Quebec, 1951 Cancer of the Lung m Canada * Aic Oraup ai-M............... l>M.................... 44-*e............... w-h.......................... Tout_____ Number :r.iu Itt.til *** ua.tn rmvnuii I* u io ioo In Cohort I* m t in * lUpport. 10*4. a nutter of the same intensity of interest as it is in younger persons. Table 18 also answers a question pre viously raised. It .iows 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 apply to the oldest group of miners. It is felt that by using the whole adult male popula tion ue ha\e developed rates for the genrrr' : "` jia:ion which are somewhat lower than if we had been able to exclude tnpeople 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 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 An Oroap UiMtrr 30 20-M 14-11 40-44 44-11 20-2* 52-V9 60-64 65-60 70-74 72-70 0-44 KMau Am 102M023 0.2 0.0 2.0 la SJ 1.2 12.7 124 IV1 10.7 144 J 11.4 24 OfbUDt Of YtAfl 1041-1042 OJ 04 24 2.4 12 2 114 774 0.7 244 06 20.0 274 H4 7.1 1020-1022 1.0 04 2.U 04 167 274 20.T 774 105 6 64 04 20.7 714 124 * "Morulliy Item Lane Ctnnr in Canulu." IUI u> 1*45. increase is particularly marked after age 50, confirming an observation previously made, to the effect that until recently lung cancer has probably been underdiagnosed in the older age groups in the general impu tation. 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 Are Group 20- * i 4J S4 55-64 65 + Rat* S * 69 9095 These rates are. in general, lower than those developed for the total (proved and suspected ) cases of lung cancer among the asbestos miners. The only large difference, however, is in the age group of 65 years and over, and it is quite possible that the rate for this group may ha\e increased for Canada between 1952 and 1954 as it did for the Province of Quebec (Table 17). A further comparison has been made w ith 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 Brou 647 v A M. A ARCH11 ES OF ISDUSTRIAL HCALTH T.\*ce 21 --Xiimber of Death] and Death Rates 100.000 by Aae Groups for the Adult Male Population of the United States * a Qreup 90-44 45-M tor Taut Population 34.544,000 4.540.QUO 5.470.000 44,414,000 Com M 1*74 4.354 4.445 14.540 lure pv ii J.4 54.4 91.4 114 J n.a * Dtu frets "Viui Sutuua at tb Cured Sum." v|. 1 ana 11MZ 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 population 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 8. 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 rates are for males of all ages. N'evcnhcicis they. too. compare favorably with the rate- of 25 for 34 for total cases! ant one the asbestos miners Turnmc t'jr 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 just discused. who have no exposure) an interesting observa tion can be developed by deduction. Hueper s* has stated that there are about 35,000 yiersons 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 648 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 asbestos 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, Chateaugav. 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 proximity to the asbestos mines include Anhabaska. Beauce Drummond. Frontenac. Megantic. Rich mond. Shcr&r'V'ke ar.d Wolfe Table 22 shows th, nur.U-r of lung cancer deaths for the years 1950 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 Vol. 17, June. 195t / LCXC CAXCER IX ASBESTOS MIXERS Table 22--Xumber of Lung Cancer Deaths and Rate per 100.000 Mon-Years CsoBUtl Mk Lent Ctnar Dmihs Aduit Mol* Pooulnoon 1U2 1M0 1M1 1952 1413 1954 Mmatic Count* EMM A<Jim Coubiiu EtCM Moetad Counu*t protioe* o( Quotas 13.100 tt.too 13.000 UM.000 ] 7 1M I J 1 SO 34S3ft II3tI 301 4flt 309 4 )ft 337 frovUMt 01 Quctac ka tfM "odMoat" oouniMi Mostml ot Ilk do Joou* 1.100.000 JM.000 10 I *17 7 aMsi ainr 2li9fftt 341 22ft * It k ----* u*i tii oak Iunt eoootf diuk oaaund Mur too JO. Total 1ft ft* 143*94 IftTO no Jut* ntf 100.000 iM S994Ji at 32J 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 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 1930 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 any greater incidence of lung cancer than those who live elsewhere in the Province. Comment on All Recorded Lung Cancer Cases, Living and Dead, among the Asbes tos .Ifiners--Although a simple enumera tion of all the known or suspected caes of c.mc*r 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 inve,ieation, there were nine proved cases and three suspected cases in the cohort. Through 1956 and to dale in 1957, there were eight deaths, six of which were merely Bratm--Tman 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. Onlv 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 prowd lung cancer cases in which we have in formation regarding the presence of asbestosis. 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 649 A M. A. ARCHIVES OF INDUSTRIAL HEALTH and txposure 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 , runes in Quebec, based on their medical records A cohort was defined as a group of asbestos miners having at least five years of exp^ure and who were in the industry in 1950 Data relative to their characteristics were collected and their status at the end erf i t-.x-ye.tr period of observation was de termined In the case of those who had <K'd an exhaustive search of death csrtifwate; and insurance records wa; carried out m order to determine as nearly as possible the exact cause of death. Mortality rates f rom 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 6S0 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 20 years. Thirty 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 Ihe 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 no: appear to increase with length of ex posure or with degree of exposure, a fact wh-ih .-"`ns 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 rat$ 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* Vol. 17. /umr. 19.V t7 o LL'XC CAXCER IX ASBESTOS MIXERS of 3".2, 25.3. and 28.0 obtained from various sources for adult males in the United S;aies. Finally, in this matter of comparison, it would appear that the world-wide experience of persons exposed to asbestos dust is not 6. Llclirens, W. Experimental Asbestosis, Schweiz Ztsclir allg. Path 14:275-297. 1951. 7.i Behrens, \V,, Jr.: The Clinical Picture and Pathology of Asbestosis, Ztsclir Unfallmed u Berutskrankh 45:129-140 (June 15) 1952. 8. Berblmger, \V.: Increase of Lung Cancer worse with respect to lung cancer than that and Diseases Due to Dust Inhalation, Med. Kim. of the unexposed population. The counties surrounding the asbestos- producing areas, in which tt is presumed most of the asbestos miners live, have al 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. most identical mortality rates with those of 11. Bohme, A.: Results of Periodical Examina eight counties widely scattered through the tions of Workers in an Asbestos Factory, Beitr. Province, and are lower than those for the 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 the diagnosis of primary cancer of the lung may be considered to have been 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. L.; Rasmussen. G.. and Abrams. H. K.: Occupations and Cigarette proved. Approximately half of these cases Smoking as Factors in Lung Cancer, Am. I. were associated with asbestosis. All but one Pub. Health 44:171-181 (Feb.) 1954. died in the recognized "cancer-age" and at 14. Bristol, L. J.: Roentgenologic Aspects of least one-third had only the lightest ex Silicosis and Asbestosis, A. M. A. Arch. Indtist. posure i Category II to asbestos dust. Health 11:189-195 (XIarch) 1955. 15. Cancer of the Lung: An Evaluation of the > On the basis of what are believed to be Problem, Proceedings of the Scientific Section, complete and reliable data, it seems fair to Annual Xfeeting. American Cancer Society. Inc.. conclude that the asbestos miners in the Nov. 3-4, 1953, Nev York. American Cancer Province of Quebec do not have a signif Society, lne., 1956 icantly higher death rate from lung cancer than do comparable segments of the general population Furthermore the death rate from lung cancer in the areas contiguous to the asbes 16 Cartier. P. Asbestosis Cancer of the Lung, in discussion on Smith. W. E.: Survey of Some Current British and European Studies of Occupa tional Tumor, Problems. A. M A Arch Indust. Hyg 5 262-263, 1952 17 Cartier, P.: Some Clinical Observations of tos operations i- comparable to that in areas Asbestosis in Xfine andMill Workers, A M A widely scattered throughout the Province of Arch lndust Health 11:204-207 (March) 1953 Quebec and i- lower than in some urban ized area- within the Province. 18 Clerens. J : Research into Pulmonary Asbes tosis in Belgium. Arch be!ce med Scc-.aie 357563 (Nov ' 1931 REFERENCES 1 A!*<<:i" Escolar. R - Bronchial Carcinoma Renew oi 200 Cases. I Internal Coll Surgeons 26 375-379 (Sept ) 1956. 2. Allen, XI. L.: Bronchiogenic Carcinoma As sociated with Pneumonoconiosis: Report of 2 Cases. J. Indust. Hyg. 16:346-347 (Nos-.) 1934. 3. Cartier. P.: A Contribution to the Study of Asbestosis. Arch. mal. profess. 10:589-595, 1949. 4. Anderson. C S, and Diblc, .1. H.: Silicosis and Carcinoma of the Lung, .[ Hyg. 38:185-204 (March) 1938. 5. Baader, E W.. Asbestosis, Deutsche med. Wchnschr. 65 407-108 (Mareh 17) 1939. ! CNne- Ar<s - ' and h.'io,-* L*r:- 1 .370. 1931. J 20 Comn. G J . Dv-yet, H C.\ Maier, H C.; Pardee. H. E. B., and Wynter, E. L The Effects of Tobacco Smoking. Panel Meeting, Bull. New York Acad. Med. 32:133-156 (Feb) 1956 21 Cohan, E. XI.: Lung Cancer and Economic Status, Cancer 8:1126-1129 (Nov-Dec.) 1955. 22. Cooke. W. E.: Pulmonary Asbestosis, Brit. M. J. 2:1024-1025 (Dec. 3) 1927. 23. Cureton, R. J. R.: Squamous Cell Carcinoma Occurring in Asbestosis of the Lung, Brit. J. Cancer 2.249-253 (Sept.) 1948 24 Cutler. S. J.: Schneiderman, XI. A., and Greenhouse, S. W.: Some Statistical Considera- B rtnm--Tnan 651 /V A. U. A. ARCHIVES OF INDUSTRIAL HEALTH tiixii in the Study of Cancer in Industry, Ant. J Pub Health 44:1159-1166 (Sept.) 1954. 25. Davies. D. F.: Current Status of Lung Cancer Research: Some Pathogenetic Aspects. CA 6.169-174 (Sept.) 1956. 26. Desmeules, R; Rousseau, L.; Giroux, M., and Sirois, A.: Asbestosis and Pulmonary Cancer, Sematne de hop. Paris 23:1820-1823 (Aug. 7) 1947. 27. Doll, R: Bronchial Carcinoma: Incidence and Aetiology (Milroy Lectures, abridged), Brit. M. J. 2:521-527 (Sept 5); 585-590 (Sept 12) 1953. 28. Doll. R_: Mortality from Lung Cancer Among Asbestos Workers, Brit. J. Indust Med. 12:81-86, 1955. 29. Donnelly, J.: Pulmonary Asbestosis, Am. J. Pub. Health 23:1275-1281 (Dec.) 1933. 30. Dorn. H. F., and Cutler, S. J.: Morbidity from Cancer in the United States, Pub. Health Monograph No. 29, P. H. S Publication No. 418, U. S Public Health Service, 1955, 121 pp. 31. Dom, H. F.: Cancer Morbidity Surveys: A Tool for Testing Theories of Cancer Etiology, Am. .1. Pub. Health 45:615-621 (May) 1955. 32. Egbert, D. S., and Geiger. A. J.: Pulmonary Asbestosis and Carcinoma: Report of a Case with Necropsy Findings, Am. Rev. Tuberc. 34:143-150 (July) 1936. 33. Ellman, P.: Pulmonary Asbestosis: Its Clinical, Radiological, and Pathologial Features and Associated Risk of Tuberculosis Infection, J Indust Hvg. 15:165-183 (July) 1933. 34 Ellman. P : Pulmonary Asbestosis. Proc Roy Soc Med. 34:557 (July) 1941. 35. Feil. A. Pneumoconiosis in Asbestos Workers. Presse med. 39:1872-1874 (Dec 19) 1931. 36 Fuliou. W E.: Dooley, A.; Matthews, J L.. and Houtt. R. L.. Asbestosis: Part III. The Effects of Exposure to Dust Encountered in Asbestos Fabricating Plants on the Health of a Group of Workers. Special Bulletin No. 42. Perjtsyi.a-.ui Deparrment of Labor and Industry. Bureau oi Indus*. Standards, Sept. 20, 1935 37 Gardner. L U. and Cummings, D. E: Studies on Experimental Pneumoconiosis: Inhala tion of Asbestos Dust; Its Effect upon Primary Tuberculous Infection. J. Indust. Hyg. 13:65-81 (Feb ); 97 (March) 1931. 38. Gilliam. A. G.: Mortality Trends in Lung Cancer, Cancer 8:1130-1136 (Nov.-Dee.) 1955. 39. Gilliam, A. G.: Mortality Attributed to Lung Cancer in the Large Cities of the United States in 1948 and 1949, J. Nat. Cancer Inst. 15:1307-1312. 1955. 40. Glovne, S R.: Two Cases of Squamous Carcinoma of the Lung Occurring in Asbestosis, Tubercle 17:5-10 (Oct.) 1935. 652 4|. Gloyne, S R: Pneumoconiosis: A Histo logical Survey oi Necropsy Material in 1205 Cases, Lancet 1:810-814 (Apnl 14) 1951. 4Z Gloyne, S. R A Case of Oat-Cell Car cinoma of the Lung Occurring in Asbestosis, Tubercle 18:100-101 (Dec) 1936. 43. Gloyne, S. R-, and Merewether, ERA: Asbestos, Occupation and Health, Supplement to Encyclopedia on Occupation and Health, Geneva, International Labor Office, 1938. 44. Goldblatt, M. W., Goldbiact, J.: In dustrial Carcinogenesis and Toxicology, in In dustrial Medicine and Hygiene, edited by E R A Merewether. London, London, Butterworth & Co., Ltd., 1956, VoL 3, pp. 185-188. 45. Haenszel, W. M.: Epidemiological Tests of Theories on Lung Cancer Etiology, Pub. Health Rep. 71:163-172 (Feb.) 1956. 46. Hammond. E. C. * Lung Cancer and Com mon Inhalants, Cancer 7:1100-1108 (Nov.) 1954. 47. Hammond, E C. Etiology of Bronchiogenic Carcinoma, CA 6:156-168 (Sept) 1956. 48. Holleb, H. B,, and Angrist, A: Bronchia genic Carcinoma in Association with Pulmonary Asbestosis: Report of 2 Cases, Am. J. Path. 18: 123-135 (Jan.) 1942. 49. Hornburger, F.: The Co-Incidence of Primary Carcinoma of Lungs and Pulmonary Asbestosis: Analysis of Literature and Report of 2 Cases, Am. J. Path. 19:797-807 (Sept.) 1943. 50. Horn, D. Is Lung Cancer on the Increase? Evaluation of Presen: Day Evidence: Cancer of the Lung, Proceedings of the Scientific Section, Annual Meeting, American Cancer Society. Inc., Nov. 3-4, 1953. 51. Komig. F. Clinical Considerations on the Question of Industrial Cancer of Asbestos Work ers, Ztschr Krebsforsch 47.281-287, 1938 52. Hueper, W. C. Cancer in Its Relation to Occupauon and Environment, Bull. Air. Soc Control Cancer 25:63-69 (June) 1943. 53. Hueper, W. C.: Significance of Industrial Cancer ir the Problem o: Cancer. Gccup Med. 2 190-200 (Sept ) ]<*/. 54 Hueper. W. C : Environmental and Occupa tional Cancer, Public Health Service. Supp 209. U. S. Public Health Service, 1949. 55. Hueper, W. C.: A Methodology for Environ mental and Occupational Cancer Surveys, Public Health Monograph No. I, P. H. S Publication No. 12, U. S. Public Health Service, 1950. 56. Hueper, W. C.: Environmental Lung Cancer. Indust. Med. 20:49-62 (Feb.) 1951. 57. Hueper, W. C.: Occupational and Environ mental Pulmonary Cancers with Special Reference to Pneumoconiosis, Proceedings, 7th Saranac Symposium on Pneumoconiosis, 1952. 58. Hueper, W. C.: A Quest into the Environ mental Causes of Cancer of the Lung. Pub. Vol. 17. Jw*. 19St LUNG CASCER IN ASBESTOS MINERS Health Monograph No 36, P H. S Publication No 432. U. S Public Health Service, 1955. 59. Hueper. \V. C.: Environmental Causes of Cancer oi the Lung other than Tobacco Smoke, Dis. Chest 30:141-158 (Aug.) 1956. 60 Isselbacher, K. J.; Klaus, H.. and Hardy. H. L.: Asbestosis and Bronchogenic Carcinoma: Report of One Autopsied Case and Review of Available Literature, Am. J. Med. 15:721-732 (Nov ) 1953. 61. Kennaway, E. L, and Kemuway. N. M.: A Study of the Incidence of Canaer of the Lung and Larynx, J. Hyg. 36.236-267 (June) 1936. 62. Kennaway, E. L., and Kennaway, N, M.: Studies of Incidence of Cancer of the Lung and Larynx, Brit. J. Cancer 5:153-158 (June) 1951. 63 Klotz, M. 0.: Association of Silicosis and Carcinoma of the Lung. An. J. Cancer 3S:38-49 (Jan.) 1939. 64 Lania. A J ; McConnell, W. J., and Fehnel, J W.: The Effects of the Inhalation of Asbestos Dust on the Lungs of Asbestos Workers: Pre liminary Study, Pub Health Rep. 50:1-12 (Jan. 4) 1935 65. Lanza, A. J., editor' Silicosis and Asbestosis, New York and London, Oxford University Press, 1938. 66. Lew, E. A.: Use of Life Insurance Com pany Records for Cancer Studies, A. M. A. Arch. Indust. Hyg. 5:198-203 (March) 1952. 6* Linzbach, A. J., and Wedler, H. W.: Occu pational Cancer among Asbestos Workers, Arch, path. Anat. 307:387-409, 1941. 68. Lynch. K. M., and Smith, W. A.: Pul monary Asbestosis: Carcinoma of Lung in Asbesto-Silicosis, Am J. Cancer 24 56-64 (May) 1935 69 Lynch, K M., and Smith, W. A.: Pul- nvr.iry Asbestosis A Report of Bronchial Carcir.T.a and Epithelial Metaplasia. Am. J Cancer _36 567-575 i.Vjg ) 1939 TO Liner.. K M., and Cannon, W. M . Asbest->?is Ana: .s:s o: 40 Necropsied Cases. Dis. Chest 14 -74-V -' . Nos -Dec.) 1948. 71 Mcr'neeters. S E. A Survey oi a Group oi Employees Exposed to Asbestos Dus:. J incus: Hyg 18.229-239 (April) 1936. 72. Merewether, E. R. A.: The Occurrence of Pulmonary Fibrosis and Other Pulmonary Affec tions in Asbestos Workers, J. Indust. Hyg. 12: 198 (May); 239 (June) 1930. 73. Merewether, E. R. A., and Price, C. W.: Report on Effects of Asbestos Dust on the Lungs and Dust Suppression in the Asbestos Industry, London, His Majesty's Stationery Office, 1930. 74. Merewether, . R. A : A Memorandum on Asbestosis, Tubercle 15:109, (Dec.) 1933; 15: 152 (Jan.) 1934. 75 Merewether, E. R. A.. Annual Reports of `the Chief Inspector of Factories, London, Hu Majesty's Stationery Office, 1947. 76. Merewether, E. R. A., editor: industrial Medicine and Hygiene, London, Butte'worth & Co.. Ltd., 1956, Vol. 3. 77. Kordmann, M.: The Industrial Cancer of Workers in Asbestos. Ztschr. Krebsforch. 47:288302, 1938. 78. Nordmann, M., and Sorge, A.: Pulmonary Cancer Produced by Asbestos Dust in Experi mental Animals, Ztschr. Krebsforch. 51:166-182. 1941. 79. Phillips, A- J.: Mortality from Cancer of the Lung in Canada (1931-1952), Canad. M. A. J 71:242-244 (Sept.) 1954. 80. Saupe, E.: Further Contributions to the Roemgcnologial Diagnosis of Asbestosis, Arch. Gewerbepath. u. Gewerbehyg. 9:391-406. 1939. 81. Smith, K. W.: Pulmonary Disability in Asbestos Workers, A. M. A. Arch. Indust. Health 12:198-203 (Aug.) 1955. 82. Smith, L W.: Pneumoconiosis and Lung. Cancer with Special Reference to Silicosis ami Asbestosis, Compent. Med. 2:3-10 (Nov.) 1949. S3. Smith, W. E.: Survey of Some Current British and European Studies of Occupational Tumor Problems: Part III. Asbestos, A. M. A. Arch. Indust. Hyg. 5:242-263 (March) 19S2. 84. Stoll. R.; Bass, R, and Angrist, A.: Asbestosis Associated with Bronchogenic Car cinoma, A. M. A Arch. Int. Med. 88:831-834 (Dec) 1951. 85- Teleky, L.: Occupational Lung Cancer. Acta Union imemat. centre Cancer 3.253-273. 1938; also. Zentralbl. Gewerbehyg. 27:33, 1940 86 Vorwald, A J.; Durkan. T M., and Pratt, P. C. Experimental Studies of Asbestosis. A. M. A Arch. Indus: Hyg. 3:1-43 (lan.l 1951. 87 Wedler, H W . Asbestosis and Lung Cancer. Deutsche med. Wchnschr 69 575-576 (Aug. 6) 1943. 88. Wegelius. C. Changes in the Lungs in 126 Cases of Asbestosis Observed in Finland. Ac:a radio! 2b: 139-152, 1947. 8 Werber. M. Pulmonary Asbestosis Asso ciated with Carcinoma. Zentralbl. Arbeitsmed. a Arbeitsschutz 2:179-180 (Nov.) 195Z 90. Wood, W. B., and Gloyne, S. R-: Pulmonary Asbestosis Complicated by Pulmonary Tubercu losis. Lancet 2:954-956 (Oct. 31) 1931. 91. Wyers, H.: Asbestosis, Postgrad. Med. 25: 631-638 (Dec.) 1949. 92. Wynder, E L,, and Graham. E A.: Elintugic Factors in Bronchiogenic Carcinoma with Special Reference to Industrial Exposures; Report of 857 Proved Cases, A. M. A. Arch. Indust. Hyg. 4:221-235 (Sept.) 1951. Braim -Truan Priaietf mi PaMukW m Ike VmMli Smtt if Amtritm 653 'if'a I .t ( 36 ' One further tntoreatlaj observation from Table U'la the rather 1 marked Increase la the total suabti of caaea far the Province between 1950 and 1955. It la assumed that at laaat part of thli Iscreate la due to Im proved recognition asd reporting of lung cancer during the Interval. For this rtaaoa. the years 1954 and 1955 wara thought to ha mora nearly repra. ' aaatatlva of actual condltloaa. Sven'so. U la quite lUtaly that the general pepalatlea la not atudled for lung cancer with the taaa diligence with which tibia dleeaae la looked for In tho minora, and It Beams probable that the mar* talily rataa for tho Province may bo low. Thla would appear to bo subs tan* tinted by the fact that the reporting of caaea la tho cohort ahowod no auch f lacraaaa over the name period. r i .7 ... > Table Lff'waa compiled to ahow the agespeclflc lung cancer i rate of caaea la which the death certificate merely read "cancer of the lung", at dlatlagulahad from tboao In which the dlagnoala waa confirmed by autopoy, urgery, or blopey, Tho term "epectflcd primary'* rofara to thoae caaea la i thaee two catogorlea In which lha tumor woe apoclflad aa having originated In lha long. It will bo noted that, of the total caaea reported In 1955. a much higher percentage than In 1954 were opacified aa primary. The table alee above that a higher percentage of the tout caaea certified la 19S5 were proved, again Indicating tacreaalag Is tara at la thla dlaeeae. 0286 / \ \ 4 :e VSI L0- * * ii* 0 - to^, ^ oj* -- -- 4 *' 3 =1 `2> Vi N f* ^ iN .1 -- 4 ^ ^ w* JIA ---- --^ l^ Zml u a3 to 0 - 4 to l to 7e gJi it m a * u IS J fl < h fe 5to fi ~ to 2 $ O ^* to to !i * 2 4^ 2s 4I u Hi to ^ toi tf* - " --4 !- *|0 ma ite mm m m MIN -* ee --- To SE 44 4to a4 to 0/> * to >5 >* ^ *2 to sm ai. to 4 a 5s e 4 c gto ttoo 4 4 "i 0 to to 4 W 5 u 1 4 el -- O <4 4 to\ * iJ .. to i0-M *: i< ? I.1' eoc oe ee o 1! * ,* is U !? 6 * * u& 0 to <2 e e oh a1 oto 4 4 4 2 O <4 ^ ' to 4 4 4 H H o * *^4tto*o0X 02S7 / \\ Ja. A comparison ha* b*n made between the 4g*.pcUic rate# iuswd ll i U Table tff. aad those for tha cohort, ahowo la Tabic f. Aa avar|* of tha 1154 cab 1955 rata* lor lb* Provlaca haa baaa used, a Lac* iba 1955 f'gur* ** higher aad may have baaa exceptional. \l Thic coosparlaoa, summarised la Table M, show* that th* observed umber *1 death* la oar aaaplo la aot Significantly greater thaa tha expected amber ol deaths, based tha average ol tha 1954 aad 1955 figure* lor the Prevlaea. It is true that, la the case ol the age group ol 45 aad over, the (W* deaths provide a llgure which le almost slgaUlcaat at the 959* level. However, It abould be aotsd that this number lacludaa oae ol the auapected bet uapreved ease* previously ralerred to. Furthermore, U la rathar lUely Ibal the rate lor tho goaaral populatloa la uaderstated la this age group, lor the obvious reaaoa that tha exact cauae at death la the very old la not a matter f tha same lateaslty ol laterost as It la la youagor persoas. TABLE 18 Ago Oreuf Comparison of the Actual aad Expoctod Number of Luna Cancer Death* by Arp Amonj Aobectoa Miner* Province Expoctod* Total Specified Primary No. ol ' I No. ol ol Death* Rat* per 100. 0U0 Miners Death* Proved l vtai 20.44 45*54 59*44 4S Uakaown 1.0 24.5 47.6 49*3 1901 1124 415 315 3 0* 2 2 2 11 1. 3 33 45 00 * Actually *4 * Th* expected number t* baaed on the average ol th* 1954 aad 1955 *g*.specific rate* lor th* provlaca ol Quebec.____________________ 022S . 39 xS Table f* also wi*cri question previously raised. It sr.^ws :i.a: tbs msmber* of tbs eobort have set died from lung conesr at so age sarltsr tbs* tbs gsacral population, and that such an oaplaaatloo eaaaot bs offered t -.V for tbs abssnes of luag caacor la 240 man with mors than 40 years of em ployment referred to on page 2b, 'It Before leering this comparison of tbe Province with tbe miners, U *'U| should be shown that their age distribution* are reasonably tbe same. That 11 tbli 1* the ease can bo observed from the following tabulatloa: n -fAtl? /7 Ag* Oistrlbutlon of Adult Malos for the Province oiCusbec. 19S1 K (Rapport, 1954) s4j As* HU Group Provtae* Humber Porccotaqo Percent*** In Cohort ..n 20*44 45*54 ;o 55*64 65* 1*1*1 a 727,135 106.952 120.944 113,467 1. 150.490 63 A 66 16 19 11 10 10 5 Too Too lc afcould b ntnimbarid tUt (ki mlaart m(U u4 coaiaqua&tly, U cm W ipctid Uit iha oUui *|i |roup will b lirgir li tbi gaatral popu* jf Ittlen. Tbe data preeeated la Table yf Indicates that tbe lung cancer rat* % n gsatrally decreases after ag* 70. Therefore, wo could aspect tho rate for l til people over 65 to be smaller than tho rate for tho group between 65 and 75. vbicb vault! apply to the oldest group of mlaore. It is fait tbet by uslsg the belt adult n-.ala population, we have developed rate* for the general popu* 40 litlen triiri or suusrbst lesc.- isa L' era t.r- bfia *; [,, u -j-ci.J* t poupls la ta fjssarsl pcpakllaa orer 73. * eoapsrisoa between t&o aaierloa utacra ud lbs pcpulatkia d tbs Dos:tales aa a vbala ves asda, sale; O etullcileal aaterial &n troa careral etwees e=S caa acwco, Phillips (77) ears ag* - # - pacific rstce tea Canada tor thre-a periods bcftro*a 3i aas 1334. Bates tee Doles ore c*?ca is Tobls fi, -^"7-- -- AgaOxosp ttsler 34 30-34 33-30 40-44 43-0 00-34 M-59 60-44 88-G3 70-74 73-70 10-04 IS plsa All ages //: -Vi 1KM3K <U 0.9 - 1.0 3.0 U (U 12.7 12.9 13.1 10.7 15.0 M U.4 3.0 > Orcvn aO ears---------- 1341-1743 ueo-us; 0.3 0.0 r . 7 1.3 S.4 uu K'.O ' ' 7 27.0 S9.T 34.3 . 10.8 S0.0 27.9 14.3 7.1 LO 0.5 3.0 0.3 10.7 ' : 37.2 ^ . 43.7 s' 77.3 102.9 56.3 v " C3.9 f 89.7 71.0 13.0 ft* iicstalUr tram fesf cs&eex la Cs soaT'U:! U Ui2 * 0290 41. Theee figure* ebew etriklagly the lacreaee la rtlti between 1551 aad i352, aad thla laereaae it particularly marked after age 50, confirm* U| aa obeervatloe prevlouely made, te the effect that until reecutly luag caacar has probably beea under.dlagaoeed ia the older age groupe la the {aera! population To uao thoeo flguroe for purpoaoe of comparieoa. It le eeceesary a cemblae the rataa for cortala ago groupe la order to coaform to the age fUtrtbutleae ueod la thla etudy. Ilace the exact populatloee la each age group lr the yeara ladle ate d le not lam. thie muet bo aa approximation. However, he ratee would bo eomewbat ae followat Affe Croup 20*44 43.54 33.44 43 Rate 3 27 43 30-3S Thcee ratee are, latgeaeral, lower thaa thoeo developed for the total (proved aad eutpeeled) caeea of luag caacar among the aabeetoe mlaere. The only largo difference, however, la la the age group of 43 yeara tad over, tad It la quite poaalble that the rata for thla group may have lacreae.id for Caaada belweoa 1332 aad 1334 aa It did for the Province of Quebec. (See Table 0231 A further corr.perUon ha* been made with eh ov*r-K rate obtained (t$m the American Cancer Society for reeplratory cancer death# in Canada Ill U 1433. THU rau, (or male*. U 20.1 par 100, 000, live more per 100, 000 that PHUllpe' 1430*1432 rato, and compare* with 23.3 per 100,000 lor proved caie* aad 33.1 per 100,000 far total caaee among the aebeetae miner* in thl* eiedy. ll U therefor* obviou* that there are no Important dUferenco* between wl lh* rate* for aehoetoe minor* and thee* for the general population of Quebec I* aad the Dominion of Canada. * Since U la probable that figure* for the Ualtod State* are more I templet* aad, therefor*, poealbly more comparable to tho data for tba minor*. i|*.*p#clftc roue w*r* compuud from "Vital SutUtlc* of the Ualhed Suit*", ii' Valaao* X and U. for 1)32. Theeo rate* have boon tabulated la Table 14. .. JJ TA33LS Number of Death* end Death Ilata* per 100,000 by Ago Qroupe far the Adult Male Population of tho UalUd Statca~Data Trom "Vital Statietica 61 a* Catted Statoo". Volamo* 1 aad U. 1932 Age Croup 20*44 43*14 * 13*44 41 * > - Tout Population 24, 344,000 0,043,000 4,340.000 5, 610, 000 44,419.000 Caaee 003 2999 4234 4403 - 14,599 Rate par 3.4 34.9 90.4 114.3 TT7I 0292 It t* apparent that the** rat** C"m;ir# favorably with :ho* fer th* ab#*te* miner* a* hown Ln Table V. Still otber'rata* lor the United Itau* wer* obtained Irorr. the American Caaeer Society, and lor r..al#*, that* **r 15.3 per 100,000 Is 195), and 2S.0 per 100,000 In 1955. They ar* eel Identical with th* rate calculated Irom th* figure* *1 th* office of Vital SutUtic*. but thl* la poaalbly because the American Cancer Society rate* are fer male* of all ages. Nevertheless, they, toe, compare favor* ably with the rate* of IS (or 34 for total case*) obtaining among the asbestos * miner*. Taralng for a moment to a comparison between th* sabesto* miner* sad person* who are eapoeed to asbosto* la one form or another (a* dlllagi*hd from th* genoral population groups Just discussed, who have no (58) tpecure) an Interesting observation can bo developed by deduction. Hooper bs* stated that there ars about 35, 000 parsons eapoeed la the United States, sad w* have found that th* Canadian mines outplay about 8.000. Elsewhere. U ha* boon estimated that the workers in England who have espoture total between 3,000 and 5,000. With worhere in Africa, Denmark, Norway, and ether countries, at least 50. 000 persons must be ospoeed throughout the world, ssd It can bo assumed that thl* number has boen fairly constant la the 20 year* llac* 1935 when th* first case of asbesiotl* with lung cancer we* reported. At l**t a million maay*ar* of enposur* ha* thus been accumulated, and Ibt* figure can be divided by th* approalmatoly ISO caso* of luag cancer with sb**>**i* reported during th* 20year period. Thl* gives a rate of 15 per U0.900 which is at least Indicative that any lung cancer rats which can be ctlculated for workers e-tpoirrt to asbestos duct If p.o: rruch Ttitrr thin that for the unexpesed population. Camparlion Between Eight Counties Adjacent to the Aebestoe-Producing Arons ted rifht Selected Counties To compare lung cancer mortality.ratoa in the counties surroundtag the asbestos-producing areas with another group of counties in which es asbestos minors are llkaly to reside, the rates were computed on the heels of figures for the years I9S0 through 195S. The eight counties selected for comparison were *rgeaiouil( Chatoaugay, Montmagay, Portacui, gtchlieu, Rlvlere-eu-Loup. St. Hyacinths, and Terrebonne, mainly because (key represent a wide geographic distribution throughout the Province. The teualios selected because of tholr proximity to the asbestos mlaoe leclude Arthahaska. ficauco, Druamoad. Prontonac, Megaatlc. Richmond. Shorbruoko, A sad bsUi. Table )4 ebows the aumbor of luag cancer deaths for the years DM through 19SS for each of these counties, and a mortality rato, based on fce adult male populatloa la 1111, To omphaoiee the comperteoo, Megaatlc Couaty has beea shews eeparately, aa has tha Proviaes of Cuoboc aad also tho Province with tho sight "aahssUis-produclng'* counties subtracted. Because ef Ite unique luag cancer deetb rate. Montreal at lain da Jeeue bae alae been listed In order to provide further compaction. <S. I c 0295 It la aaaum cd lh a l a ll m a le lu n g ca n ce r d ca lh e o c c u rre d a fte r age 20. 1: 1* apparent Irem (he table that th lunj eenerr death rate {or the eight esuatica la:rr.eelately urroune'.ng the aabaatoa^produciag arete it practlcally-ldaetlcnl with that of atght eounilaa aaleetod lor eor.^irnjn. While Mcgantle County haa a rate nearly twice that al the combined eight elected eouetlee. It t lower than the rata lor the Province, ecd eoaaiderably lower than the rate lor Montreal, The Hgurc lor Montreal would certainly be higher except lor the very low number# ol deatbc reported lor 1950 end 1951, and it would appoar that la (hoao yoare aome error la reporting haa . oadoubtodly boon mado. Oa tbo baala ol the other yoara, 1950 tad 1951 daatha would bo expected to bo about 00 groator, Thta would rejult in a rate ol 40 per 100, 000. The only peaalbie coeclueloa Irom tbia compartaon la that there la ao evidence that tho peraone who live and word la the couatlee aurrouadlag had adjacent to the aebectoe-produclag areae have eoy greater taeideace el lung caacer than thoee who live eleewhere la the Prov;sce. Dioouoeton-ol All Recorded hung Cancer Caeoe, Living end Peed. f.-'rros';thc Aebeetoe Mtnere Although a elmple enumeratiao ol all tha known or euepected cnaee <vl cancer ol tho lung la thoao araae hee ao particular valua Irom a etatlatical point oI view, it la el Interact to eummerlae cuch caeca ler the record. There were nine death# prter te the beginning ol the time period covered by the etudy, includlag one in which the diagnoeia wee medlaatiaal lymphoaereon-.n. 47. Durlsg the period covered by this Investigation, there were nine proved diet nd three auspectad cases to the cohort. Through 1936 end to date In 19S7, there were eight deaths, sis of which were merely suggestive of cancer of the lung end included such diagnoses as mediastinal lymphosarcoma, meso thelloma. cancer of the leg with metastases to luog. obsess of lung, and caocsr of the pancreas. One other wee diagnosed.on the basis of x-ray only, la addition, there ore now living four cases la which the diagnostic evidence is strongly suggsstlve of lung cancer. This la o total of 33 cnees of all types, including tea `'suspected" hut unproved cases, and four that are still living. The remaining 19 coastltute the total of proved casee of cancer of the lung among the asbestos misers since 1940. The proved cases averaged 59 years of age at death, and varied between 37 years aad 45 yeare. Their working spaa covered periods varytag from a minimum of 14 years to a maalmum of 37 years. Only three men bad lose than 25 yeare of employment la the Industry. Seven among those on whom such Information Is available had o weighted exposure placing them la category 111, and eta worked la an expoeuro represented by category 1. Ibere were only 17 among thoaa proved luag cancer coses in which wo have Informatics regarding the preeeace of aebeatosla. Asbestosts was present la ntae, although It was minimal la two. Two pathologists disagreed regarding Its presence la another. At least seven of the 19 proved lung cancers, therefore, were not accompanied by asbestosts. 0297 4a. Summary and Cnnrh.eten* Interact la the quaatloa of whether there may ba aa aaaeelatloa between luag eanear and aspoaur* to aabaatoa baa baen avldant a lac* tba report la 1935 by Lynch aad Smith of a caaa la which lung caacar aad aabaa* taala wara both praaaat. Aa additional caaaa la which tha two dlaaaaaa cn- aslatad wara raportad, a cauaal aaaociatloa appaara to hava baaa gradually accepted by many authora. although aoma workara conatdarad the eorralatloa OtJb la ba inconcluaiva. Tha praaaat atudy waa caaMtlaaltaad la aa effort ta dotarmlna whathar a cauaal ralatloaablp did. la fact, axlat batwaan aspoaur* to aabaatoa aad caacar of tha lung. Slaca moat aarllar etudloa had baaa Umltad to eaumaratlag the luag caacara found la eartala aalactad aamplaa, auch aa caaaa catalog ta autopay r death certlflcataa la which aabaatoala waa maatloaad. It waa apparent that *) ` they cauld not fulfill tha requirements of aa epidemiological aad atatlatlcal approach to the problem. Tha praaant atudy waa, therefore, dealgaad to meat tha requirement* of tbla method. After a preliminary survey to aaploro the availability of reliable laformatloa, data ware gathered on worker* la the aabcataa miaat in Cuabac. AS A S */* baaed aa tbair medical record*. A cohort waa defined M8*as*cw(aw*ctal* Ar- *.**/- Are /wyey / erOamanmnd^f 1-rMhori i III ` l iT'lm 1 idaril^ --'y a,a* .vaca r*a !*'****;> Data ralatlva la their characteriailce war* collactad aad thalr atatua at the and of a a Is* year parted *f obaarvatlon wa* datarmlnad. la the c*a* of the a a wh* had died, aa vshauaiiv* aaarch of death certlflcataa aad ioauranc* record* 0298 49. waa carried out 1a order to determine a* nearly a* partible the exact eaute 0/ death. Mortality rate* from lung eaacor for the general population of the Province ef Quebec and tta vartoua countlee and fer the Dominion of Canada, ac well aa the United Statea were calculated from atatlatlca collected la the appropriate placoa, Comparleoaa of the rataa obtained for aebeatos worker* and for the ether population group* were made according to accepted etatletlcal mothode^actdnlnhaxmfrwofcanplalnad la cirne detail. Record* were obtained on 6091 peraon* who fulfilled the criteria of the cohort. It waa not poaalhl* to traea 133 of thaaa for the whole period, bat 5171 of the remaining 5955 war* found to ho atUl living la 1955 or lAter. Of the 157 known dead, cancer of the lung wa* conaldered to have been reaeon* ably proved la nine and to ho atroagiy auggeated In three. The member* of tho cohort were atudlcd with raapoct to ag*. length *f employmeat, a weighted average of thalr oapoaura. and their amoklag habita. Tear thouaand. ala hundrad and aeventy-thrae were found to be amokera within the definition of that term aa uaed la thl* atudy. Thirty-four per cent I tho cohort wore more than 45 year* of age, had 30% had beea employed for longer than 30 year*. Thirty per cent had a weighted eapeaore which placed xrf them la category of hlgheat oapeeuro. The mortality rat* for lung cancer, a* computed on the baela of nine "proved" death* among the cohort waa 25.3 per 100,000. Whan tho three "Ouepectod" caaea were added, tho "total" rata for the cohort roa* 33.5. 0299 50. The importance of the auepeciod but unproved caeee la determining thoee retoe bee bote reiterated boeeuso It ie likely thei euch ceeee would not be Included la the eutletlca for tbe general populetlea ead becauee they Influence the reeulte eo markedly. According to the flndinge in tbia.atudy, the mortality rato from lung cancer doee not appear to Incroaae with length of enpoeure or with degroo of onpoeura, a font-which preeent* etroag evidence againet the carcinogenicity of eebceioe. . Comparteoa of the esperlenco among tbe aebcetoe mlnere with that of varlpue eegmento of tho unenpoeed, comparable population ahowe that the ohaerved number of deathe among the mlnere le not elgnlflcantly greater than the expected number. Tho rate for proved case* among tho nebectce mlnere (25.) per 100,000) comparoe well with the rate of 22.5 per 100,000 for tho roat of the Province, and 20,8 per 100,000 for adult mnlee throughout \ the Dominion of Canada. It alee comparoe eatlefactorlly with ratee of )7,2, 25.), and 28.0 obtained from varloua eourcee for adult malaa la the United ttatee. finally, la thla matter of comparleoa, It would appear that tho world* wide onpertenco of pereoae axpoeed to aeboetea duet le not woree with reepect to lung cancer than that of the unexpoeed population. The coualiea eurrounding tho aaboetoa*produclag arena, and la which it la preeumed moat of the aebeetoa miner a live, have almeet Identical mor tality ratea with thoae of eight countlea widely ecattared through the Province, and are lower than thoee for the remainder of the Province, and much lower then the rate far Montreal 0o0n SI. Since 1940, there have bean 19 eaaaa la which the diagnosis ol primary cancer 0/ the lung may ba considered 10 have beaa proved. Approslmately ball el these eaaaa wara aaeeelatad with aabeatoela. All but eaa died la the recognised cancer-age" aad at leaat one-third had ealy the llghtaat exposure (category I) to aeboetoe duet. . Oa the baa la oX what are believed to ba complete aad reliable data. It eeeme lair to conclude that the aabaatoa mlaera In the Province el Qaebec do not have a elgnllicaatly higher death rate from luag caaeer tbaa do com parable aegmonta ol the gaaeral population. Furthermore, the death rate Irom duag caaeer la the areas contigu ous to the aabaatoa operatloae la comparable to that la areas widely scattered throughout the Prevlace el Quebec and la lower thaa la seme urbanised areas wilhla the Province. 0301 fcibilOiTapjy 1. Alaecio, bieobtr X. Bronchial carcinoma; review of two hundred caaee. J. Internet. Coil. Surgeone. 2b: 375-379, September, 195b. 2. Alien, M. L. Bronchiogenic carcinoma aeoociated with pneumonocomoelet report of two caeee. 2. laduet. Hyg. lb: 34b-347, November, 2934. 3. American Cancer Society, lac. Cancer of the lues; ao evaluation of the problem. Proceeding* of the Scientific Section, Annual Mooting, Nov. 3-4, 1953. American Cancer Society, lac. Now York, 195b. 322 pp. 4. Andcreon, C.S. and Bible, 2.K. Sillcoeie and carcinoma of the lung. 2. Hygnae. 35: 115-204, March, 1935. 5. Boeder, . Vf. Aebeetoeie. Bcuteche mod. Wociiacbr. bS: 407401, March 17, 1939. f krone, W. experimental aebeetoeie, Scbweia. Ztecbr. Allg, / Path. U. Baht. 14: 275-297, 1951. ^ i-U* L Bokrena, W. 3r. Tke clinical picture and pathology of aebeetoeie. Z. Unfallmed. u. Berufkrankh. 45: 129-140, 2une 15, 1952. \ 5. Berbllngar, W. Inert ace of lung cancer and dleeaae* due to duet Inhalation. Med. lUln. 27: 1337-1342, September 11, 1931. 9, Berenblum, 1. irritation and carciaogeae. Arch. Path. 35: 233244, October, 1944. 10., Dokme, (i Aebeetoeie. Deulecbe mad. Wockackr. b2: 925-930, ( ' dwC. ,}!*& 11. Oohifia, A. Rcaullr of periodical examination# ol worktri In u aabeato* factory. Deitr. a. 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It 379, 1931'. 20. Collla, G.J., Duryoe, K.C., Mater, 11. C., Par doc, H.E.D., and Wyntor, li. L. Tho effect* of tobacco amoklng. Panol Mootang. Bull. Now York Acad. Mod. 32: 133.156, February, 1956. 21. Cohort, C.M. Lung cancer and economic etalu*. Caacor. I: 1124*1129, Novombor.December, 1955. 22. Cooks, W.X. Pulmonary oboatooiv. Brit. Mod. J, 2: 10241025, December 3, 1927. 54. 23. Curoton, R. J, R. S^uunoui coll carcinoma occurring in asbeetool# oi ibo lung. Brit. J. Caneor. 2> 249-233, September, 1941. 24. Cutlor, S.J., Schneiderman, M.A., and Crocnhouoo, S.W. Somo atatlaUcal conaldsratlon In tho study o( cane or in industry. Am. J. Pub. Health, 44: 1139-1106. September, 1934. 23. Davlos, D. J*. Currant status of lung cane or rosoarebi toms pathogenetic aspects. Ca, Amorlean Cancer Society, lac. 3: 169-174, September, 1936. 26. Doemeules, R., Rousseau, 2,., Giroux, 24., and Slroia, A. Amlantoso et caacero pulmonalres. Semalno do. bop. Paris. 23^1820-1623, August 7, 1947. 27. Doll, R. Bronchial carcinoma: incidence and aetiology (Milroy lectures, abridged). Brit. Mad. J. 2t 321-527, September 3, I933i 363-390, September 12, 1953. 28. Doll, R. Mortality from lung cancer among asbestos workers. Brit. J. Induct. Med. 12i 61-66, 1955. 29, Donnelly, J. Pulmonary aebestoola. Am. J. Pub. Health. 23: 1279-1281, December, 1933. 30. Dorn, 1LT., and Cutler, d. J. Morbidity from cancel in the United Stales. Pub. Hsalth Monograph No. 29. P. 11. S. Publication No. 418. Washington, U.S. Government Printing Odlcs, 1953. 121 pp. 31. Darn, H.I*. Cancer morbidity ourvoysi a tool far tooting tboorloe et cancer etiology. Am. J. Pub. Health. 45: 615-621. May, 1955. 0304 /... w* * 32. gbert, D.S., And Calmer, A. J. Pulmonary asbsstrsis and carcinoma; report of a on with r.cerepay fiadinge. Am. Atv. Tubcrc. J-i: 143-ISO, July, 1936. 55. 33. llman, P. Pulmonary asbsstosls; It* clinical rudiolOKieal, and pathological features and aasedated risk of tuberculosis la* lection. J. 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