Document 4v3wxkZD0r3Ov1gp2m438qx7x

Restricted Copy 31 CONFIDENTIAL INDUSTRIAL HYGIENE FOUNDATION OF AMERICA, INC. 4400 FIFTH AVENUE PITTSBURGH 13, PA. AN EPIDEMIOLOGICAL STUDY OF LUNG CANCER IN ASBESTOS MINERS Report to QUE3EC ASBESTOS MINING ASSOCIATION Quebec, Canada September, 1957 (50 Copies Reprinted January iQRO'i 'I ;I 1 Industrial Hygiene Found. 'ion oi America, Lnc. 4400 Fiuh Avenue Pittsburgh 13, Pa. -THea^bM- OW1 " AN EPIDEMIOLOGICAL STUDY OF LUNG CANCER IN ASBESTOS MINERS For OUEBEC ASBESTOS MINING ASSOCIATION Quebec, Canada July. 1956 to July. 1957 By j Daniel C. Braun, M.D. 7 Medical Director i i September, 195? 1 By: C. Richard Walmer, M.D. Managing Director 0127 Clamry....................................................................................................... iv 1. Introduction................................................................................................. 1 II. Critic*! Review of Liutiture.................................................................... 5 III. Principle* of the EpidemiologicalMethod................................ 13 IV. Collection end Anelyii* oi Set*....................................................... IB V. Retail* end Interpretation............................................................... 26 A*be*to*i* end Lung Cancer....................................................... 47 Comperijon of the Cohort Experience with that of the Province of Quebec, Dominion of Caned*, end the United State*.......................... 55 Companion Between night Countie* Adjacent to the Aibestoi-Pr oaucing Are** one Eight Selected Countie *........................................ 66 Di*cu*ion of All Recorced Lung Cancer Ceiei, Living and Deed, et Aabettos end Thetforo Mine*.................................................................................... 68 VI. Summery end Condition* . ............................................................ 71 VII. Bibliography.............................................................................................. 78 G12S JU ' 1HJ"*V 1. FOREWORD The success of a stucy of the type herein reported de pend* very greatly upon the availability of data from many sources, and the assistance and cooperation of those in possession of these data. Industrial Hygiene Foundation was fortunate in having the wholehearted cooperation of the asbestos-producing companies, and particularly of their medical and nursing personnel who have the re sponsibility for maintaining the medical records of the workers. In this connection, we are especially indebted to Dr_aul Cartier and his staff at the Thetford Industrial Clinic, and to Or. T. R. Grainger and the nurses at Asbestos. All records in these two medical cen ters were put completely at our disposal, and the care and complete ness with which they are matnuined assisted considerably in the preparation of the material relative to the worker population. Data on population figures and on the causes of death m the Province of Quebec were obtained with the utmost assistance and co operation from Or. Paul Parrot, Head of the Department of Demogra phy in the Ministry of Health. Not only were all vital statistics and reports made readily available to us, but Dr. Parrot and his entire staff rendered valuable assistance m many ways, including the location and interpretation of death certificates, especially helpful in this part of the work was Miss Cauihier of Dr. Parrot's staff. The same helpful 0129 u. cooperation n rendered by Messrs. Hardy anc Hopkins of ;he Sun Life Aiiunnci Company of Canada in Montreal, who made available their record* of the death claims paid under the group policy cover* ing the worker* at Asbesto*. Valuable suggestion* for the conduct of the study were made by Or. J. A. Vidal, Chairman of the Silicosis Board, and Or. Cuy, Pathologist for the Board, as well as Or. Cregoire, Deputy Min ister of Health for the Province of Quebec, and Drs. Simard, Cufresne, C and Groulx, in Montreal. Statistics for the mortality rates for the Dominion of Canada were obtained through the kindness of Dr. Dean F. Oav.es. Administra tor for Research on Lung Cancer for the American Cancer Society, and those for the United States were graciously furnished by Miss Curainick in the National Office of Vital Statistics, Department of Health, Education, and Welfare of the United States Government. Finally, the very great assistance rendered by Dr. Kenneth W. Smith, Medical Director of JchnsManville Corporation, and Mr. Ivan Sabourm, General Counsel for the Association, in making the necessary contacts, in travel arrangements, and ui so many ether ways, is gratefully acknowledged. The methodology of this research is believed to be un.que among the reported studies of lung cancer as related to asbestosis and exposure to asbestos. Assistance in planning the study in such a way as 0130 ( i ttwtim*l co assure a proper epidemiological approach, end all biostatistical applications of the fmoir.gs were provided by Mr. 7. David Train, formerly of the Graduate School of Public Health, University of Pittsburgh, and the etaff of the Industrial Hygiene Foundation. The report is believed to present the findings in an objec tive manner and is respectfully submitted for the consideration of the Association. . 0131 i ,/ ( \ ..... TIT i IV. glossary ( For the purpose of el*nty and uniformity, tie :e:--i ued is thi* report are herewith defined according to the manner of their use. Asbestos workers: Workers exposed to asbestos dust in other than mining operations. Asbestos miners: Workers engaged in the mining and prepara- tics of asbestos in the areas under study. ( Asbestosis: A generalized fibrosis of the lungs diagnos- able by x-ray, or by microscopic examina tion of the lung tissue, but not necessarily accompanied by symptoms or By disaoility. Cohort: A segment of the population, defined accord ing to certain criteria, and representative of the whole population. Specifically m this study, a group of asbestos miners having at least five years of exposure m the industry and who were lb the industry during 1950. Lung cancer, cancer of the lung: A neoplasm of the lung or bronchus, wher ever situated, and including adenocarcinoma, squamous cell, and undifferentiated, round, or "oat cell" histological types. Primary cancer of the lung means such a neoplasm originating in the lung, and not secondarily in the lung as the result of a metastasis from another primary location m the body. Smoker: As used in this presentation, the term smoker refers to a cigarette smoker, habitually smok ing more thun five cigarettes per day. Persons who smoke pipes or cigars exclusively were not considered to be smokers for the purpose of this study. ( 013 I. INTRODUCTION Ever use* the pronounced increase in the incidence o/ lung cancer among males became apparent, there have been attempts to associate it with one or another of the various elements in the en- viroaaent of man. The approach used by some workers has been to suspect one or several substaoces and then set about in an intensive search for lung cancer among persons who have had any exposure to those compounds. In this connection, Smith writes: "The ten* deacy of authors reporting the coincidental occurrence of primary lung cancer with silicosis or with any other theoretical ctiologic con ditions, has been to emphasise 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 taowa to cause a specific type of pneumoconiosis, and because persons who show this form of pneumcconiosis often come to autopsy and pro vide a ready source of material for study. It was in this way that re ports of the simultaneous occurrence of lung cancer and asbestosis be gan to accumulate after the report of a case by Lynch and Smith ^ ' m I9JS. Within the next ten years, about (5 additional cases were reported, and in 1946 Merewetber reviewed all deaths from asbestosis re corded m England sioce March, 1924, Lung cancer occurred, according 0133 2. to Merewether, in '.i.Z'', of these cases. Continuing cats study to include December, 195-4, Merewether counted 55 case* of cancer of the lung among 544 cases of asbestosis, raisins the incidence to 16?.. (92) Gloyac, whose work is also frequently referred to as establishing a connection between asbestosis and cancer of the lung, reported in 1951 the results of bis findings on 1205 autopsicd cases. This series included 132 asbestos workers, of whom 121 showed asbestosis. Cancer of the lung was present in 14. 1 % of these asbestosis cases. In 1941, Nordmana and Sorge 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 Hueper about 100 such cases bad been reported up to 1955. As a result, an associa* tion between the two diseases appears to have been accepted by many authors and several writers were using the term "asbestosis cancer" of the lung. Werber ^ * w 1952, stated categorically that in 7% to i7% of cases of asbestosis, after a latent period of about 1 1/2 to 20 years, carcinoma becomes established in the lung. On the other hand, not all authors accepted the alleged astocta- (177) tion without reservation. Saupc in 1939 had reported that he had discovered no cases of lung cancer among 620 cases of asbestosis which he had examined; and m 1942, Kolleb and Angnst expressed the opinion that the number of cases of asbestosis with lung cancer was too 0134 3. (200) small for statistical evaluation. In 1947, Wegelius reported 12b - radiological!)- ciagr.osed eases of asbestos:* among 476 worker* in I'm.And, And founs no casci of lung cancer in this group. Goldblatt and Coldblatt :n their section of Mercwether's latest book, atAte: "But At no stage in all these impressive researches was any clue obtained which might have offered any support to the possi bility that asbestos could act as a carcinogen. There is no reliable criterion by which one can anticipate carcinogenicity and, as is well known, relatively minute changes in the structure of a chemical car cinogen are sufficient to diminish or eliminate carcinogenic action. if asbestos is indeed to be regarded as a carcinogen, the need is felt to demonstrate some property which can be regarded as something more than inertness." These authors advance the theory that, until some more experimental evidence of direct carcinogenesis by asbestos or a de composition product of it can be obtained, asbestos might be considered as a "co-carcinogen" which only induces a further development of a pre- neoplastic condition brought about by something independent of the as bestos, such a* an endogenous factor. Thus the literature, while tending to support the thesis that asbestosis is in some way related to the development of lung cancer, is by no means unanimous. Altogether, it is perhaps more confusing than enlightening. 013 ..at- iiP". i. Meanwhile, the Canadian Johr.s-Manville Company m Asbestos nil been i-ert to the whole problem, and at the Thetford Inausirtal Clime, Or. Paul Cartier wti studying the situation among a working population of about 6000, and made notable contnbutton* to the literature juet eited^***\ Between these two areas, a number of cases bad been recognized and tabulated by the spring of 1966. At this time, at the suggestion of Dr. Kenneth W. Smith, Medical Director of the Johns-Manville Corporation, and Dr. Cartier, the Quebec Asbestos Mining Association approached Industrial Hygiene Foundation to determine whether it would be feasible to conduct an epidemiological study in orccr to discover whether the incidence of lung cancer was, in fact, greater among asbestos miners than among tuc general popula tion, and whether there was a correlation between lung cancer und the disease asbestosts. The Foundation submitted, in March, 1956, a pro posal tor such a study based upon a preliminary survsv of the type and accessibility of data which might be available. This proposal was ac cepted by the Association through its Secretary, Mr. W. H. Soutar, and its General Counsel, Mr. Ivan Sabounn, Esq. 0125 / a ! II. CRITICAL ftsviiw of LITEPATv'Si i | A careful review of (he published material on (his sub* l ject shows (hat the majority of the reports are clinical and not epi demiological. They lack many elements necessary for the applica tion 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 conclusions and generalized beyond the scope of the works which they quote. Nowhere, for ex ample, have we found references to a population or asbestos workers, although several authors who have quoted the observed incidence of lung cancer in autopsies of persons who also had asbestosis imply that this incidence applies to asbestos workers. We have likewise been unable to find any study which actually calculated the incidence of lung cancer among a population of persons who had asbestosis, and not just those who came to autopsy. With the exception of a paper by (63) Doll , none of those reviewed gsve any data on exposure and dust concentrations, and even Doll's paper merely mentions "scheduled" sreas, by which is meant, "those areas wher* processes arc carried on which were scheduled under the Asbestos Industry Regulations of 1931 as being dusty," There is, furthermore, a complete lack of definition of \ terms ss used in the published literature. For example, the term 0137 jt o. 'asbestosis", as usee, may refer to changes obscrvacie or../ by microscopic examination ol the lung tissue, or it miy mein a radiologicallv detectable condition. Mott of the published reports obviously included women among their cases, but some of them do not give the number or pro* portion of women involved m the study. There is also a lack of uniformity as to what type of ex posure most studies have dealt with. Of 99 cases enumerated by Kueper ^ in 1955, only ten appear to have originated in the United States, and seven in Canada. Some of the earlier reports apparently included asbestos miners, but it can be assumed, since 82 of the 99 cases bad originated m England, and since no asbestos mining opera tions ere 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 this understanding of the limitations of the existing literature with respect to epidemiological generalisation, it may be of value to consider in somewhat more detail some representative earlier publications, a few of which were referred to briefly in the previous section. 7. Cne bf tne mss', ceta.iec studies and one which deserves (63) the most serious csr.i.ctrmon is that reported by Doll in 1955. Thu study reviews causes of death among asbestos workers based on coroners' records. It also attempts to estimate the risk by study ing records of mco who worked for at least 20 years is exposed situa tions. Doll concluded that lung cancer was a specific industrial hazard of certain asbestos workers and that, after 20 years of exposure, the risk is ten times as great as for the general population. This article is important for several reasons, 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 num ber of cases (bl cases of lung cancer) suggests---but docs not prove -- that lung cancer is an occupational hazard of asbestos workers." Neither this article or any previous one which we have examined presents any figures to prove that asbestosis is an infrequent occurrence. Es timates 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 asbestosis 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 1,0-42.25 man years of life. It is also true that in selecting men whs had been employed for at least 20 years, the study suton.utically excluded those who died from other causes after shorter employment. A4 * hr 1: a.so seems mat this rev-.cw does not ice any new cases ie the literature, although Hueper m enumerating 99 cases reported prior to 1955, lists 11 discussed in it. Clearly, also, the paper is not dealing with asbestos miners. Another reason why this publication is of importance is 4 statement which it contains to the effect that "the strongest evidence that it (lung cancer) may be a haaard (in asbestos workers) has been produced by Merewcthcr and by Gloyne." An examination of these references leaves at least some question as to the strength of the evi dence produced. (92) In 1951 Gloyne presented a review of 1205 autopsies on persons woo had worked in various dusty occupations. This num ber included 132 asbestos workers, of whom 121 showed "pneumoconiosis" --presumably asbestosis. Primary cancer of the lung occurred 17 times in this group, an incidence rate of 14. If. for lur.g cancer among autoosiea asbestosis cases. There were in his series 796 cases with silicosis, and 6.97. of these also showed primary cancer of the lung. The incidence of lung cancer in other forms of pneumoconiosis was 6.7f.( and in le1* cases winch proved not to have any type of pneumoconiosis it was S. 3r>. Gloyne considered "the mortality of the asbestos workers" to oe "Disturbing". Pirst of all, it is obvious that the paper does not deal with the "mortality of asbestos workers", and secondly, it must be borr.e m mine that all of Or. Gloyne' cases were submitted to him 0140 :..r study because the findings were unusual for uncomplteated pneumo- . Presumably, ail cases, including those ol asbestosis, in huh the fir.cmgs were not considered unusual were never brought to Ur. Cloyne's attention. As a matter of lact, in the same paragraph in which he expresses concern over the incidence rate in asbestosis, Ur. Gloyne himself points out that the rate for lung cancer based on ix-cropsies at the London Chest Hospital was 21. 3% while the figures ut the Registrar-General showed only 2.4%. He thus recognized that autopsies on a certain selected group of cases were not representative ,f ibe general population. It would seem, then, that notwithstanding mi value of Or. Gloyne's work, its importance as an index of the pre valence of lung cancer in asbestotics has been misinterpreted by those *iio have quoted him. All that it really shows is the fact that in a group .. .1. cases, selected for special study primarily because they seemed ,internal by preliminary examination, 17, or 14.1% had lung cancer. Mercwether in 1*47, m the report of the Chief In spector of Tactones, reviewed all cases reported between 1924 and ,*4o in which asbestosis was the cause of death cr a coexisting con dition. This work was later extended to include all such cases reported up to iVeember, 1954, by which time there were 344 deaths including 2-,5 males anc 1 J J females. Among them were 55 cases (16%1 of cancer ot the !ur.g, 41 m males and 14 in females. It is quite possible that a large number of asbestotics who did not die of their asbestosis, or m 10. >he* death certificate it not mentioned, may have been missed. The import o: this 16T* is enhances by the simultaneous statement that the incidence of lung cancer m autopsies of the general popu lation is only IT*. The danger of attempting to compare a rate found in 344 cases with the rate for the general population without respect to age, occupation, and many other variables, such as smoking habits, is obvious. Lynch/14** who with Smith had reported the first case m 1933, reported four cases of carcinoma of the lung in a series of 49 autopsies on workers m an asbestos manufacturing plant who were shown to have "demonstrable deposits of asbestos in the lungs." This, of course, is not necessarily identical with the disease asbes toses. Lynch, himself, points out that, although this is an incidence of t.1%, "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 asbesiosis. It is of interest to note that Klotz ^*** found only four in stances of lung career in 47S cases of asbestosis, a series 11 times as large. Behrens, as quoted in Merewcther estimated that, of 30* cases of asbestosis in the literature, 44 showed associated cancer of the lung--giving an meioence of 14. Zf*. This is another case of generalizing an incidence obtained in a group of cases which were 0142 >* l-we**1 n. undoubtedly reportes only bccauj^ tome of them showed lung cancer, to posftbly eundreaa of asbestotics who*e cases were never reported. The same applies to the conclusion of Tcleky who appears to have reviewed reports of 39 autopsies on persons with asbestosis among which six cases of lung cancer occurred. Information from those sources does not justify generalizations with regard to mortality rates. (J05) Werber who made the unequivocal statement that lung ( cancer would result in from 7% to 17% of cases of asbestosis, allowed himself consideraole latitude by qualifying it, as regards time, to an interval of 1 1/2 to 20 years. Finally, mention should be made of some entirely unsupported statements which tend to build up a mistaken view. point through mere repetition. One example is a sentence in "Nontubcr* - (761 culous Diseases of the Chest" where the authors say simply, "an ex* ccssive incidence of pulmonary cancer has occurred among workers in other occupations, such as asbestos industries, nickel-copper refineries, stokers in generator plants, etc." without substantiating reference. As an illustration of the case with which a few reports which merely suggest a certain conclusion can, through the lack of a sufficiently critical attitude, be summarized to produce the conclusion in a definite (69) form, an editorial in the Journal ot the American Medical Association mentions the work of Wedler and the report of Merewether and then es tablishes the causal relation between asbestosis and cancer of the lung as { settled. As a final convincing argument, it refers to "recent experimental 0143 12. observations (by) Nordrr.ann ar.d Sorge . This u tie experiment in which squamous carcinoma wu md to have been procuces in about a dozen white mice, And which has not been duplicated by uy other in vestigator! Perhaps no one has written so extensively or so dogmati- (lOS-124) tally on the subject ss hss Kueper , la 1955 be reviewed the esses reported prior to that date and enumerated a total of 99. leven of these were those discussed by Doll (63) and appear to have been cases covered by other authors. igbt were discovered by Ksnnawiy and Kennaway * ^ in an analysis of death certificates and, unless Merewethcr's study was incomplete, these cases should have been in cluded in his report. Of the remaining SO, it is quite possible that the 31 contributed by Merewetber and the 17 by Gleyne contain some dupli cation with eacn other or with other nglish authors. In the same paper, Kueper dismisses the idea of determining the frequency of pulmonary cancer among the total worker population of the asbestos industry on the grounds that it is immaterial how many workers in the industry develop lung cancer, since some of them have no exposure and therefore do not develop asbcstosisl / jtmmrn it* 13. Ui. PRINCIPLES OF THE EPIDEMIOLOCICAL ME7HC3 - A* das beer. indicated, much of whit i now thought to be pertinent concerning the comparative frequency of lung cancer in different population group* he* been developed from the analysis of clinical material, particularly surgical And autopsy record*. This he* been supplemented to some extent by the reported impressions of esnous clinicians bused upon their personal observetions. More re* cently, however, attention has turned to the systematic investigation of this problem by the same methods that have proved so successful previously in the study of communicable diseases, that is to say. by epidemiological method*. Epidemiology is the method of investigating a specific disease in human populations in relation to certain variable character istics, including the environment. In contrast to the clinical method which is primarily concerned with the characteristics of the disease is individuals, epidemiological research involves the investigation of the disease as a mass phenomenon. It seeks to discover what propor tion of persons in a given set of circumstances will eventually develop the disease. Epidemiology cannot predict whether a given individual will fall victim to a specific disease, but it can predict the approxi mate Dumber of cases of this disease which will develop in a population if specified sise, composition, and subject to a given environment. It 0145 u. procC by first cirnuily and accurately describing character istics s: the disease i.n different population groups and its essential objective is the formulation, testing, ar.d verification of generalitations concerning the disease in question. In order to apply this method of investigation to the pro blem under discussion, the Foundation was of the opinion that a srudy should be planned so as to provide: 1. A well defined population group. 2, Available data for all members of this pop ulation, including the healthy as well.as .the ill. 2. A sample which is truly representative of the population. 4. Reliable ar.d valid observations relating to the problem of the study. A serious defect, common to most of the studies which have been reported, is that little or no information concerning the ' healthy people in the group seems to have been available to the author. Therefore, results of these studies cannot properly be generalized to include such people. In order to draw a generalization regarding all asbestos workers,:! is necessary for a study to include living persons as well as the dead. Limiting the investigation to auton.ticd cases, as has been frequently cone in earlier studies, still further restricts its use 0146 15. ;n gne n.isatiop.. The problem with which the C-3cc Asscilsi Mining"Associa:;on u concerned i* whether asbestos miners ex* pcricnce more lung cuicer chan does the general population. The answer necessitates the collection of reliable information on asbestos miners as a group, as well as on the general population. It seems advisable to discuss the differences between the epidemiological approach and that used in the studies which have been reported to date. A very important consideration is the fact that lung cancer, in spite of us 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 oe stuoied to proviac meaningful results. Recognizing the difficulty of obtaining such large samples, most earlier writers deviated from the epidemiological method and eought to circumvent the requirement of observing well persons by; I l. Comparing the relative frecuencv of cancer in various sites. Z. Comparing the relative frequency of cancer in a group of hospitalised patients. 3. Comparing the relative frequency of cancer in a group of cases coming to autopsy. The frequency of cancer of the lung relative to the total of all types oi cancer may be increased merely by reason of a deersase 0147 16. in the tr.ctaer.ee o.' cancer of other sites. This could be true even though the xr.cicer.ce of lung cancer remtuiet constant, or u xt de creased lest rapidly than that of the other types. Attempting to compare two population groups, loo'mng only at the relative frequency of cancer in various body sites, may result in finding a higher percentage (relative frequency) in one of the groups, when, in fact, the mortality rate of cancer of a particular organ is ex actly the same m both groups. This is because the relative frequency of cancer in other organs may be lower in the second group. The mor tality rate from a particular cause is the true mcarbre of comparison. It is apparent that selected groups such as hospitalized patients or autopsy cases may not be representative in any way of a larger group, and that in dealing with such samples, the observer may easily find more case* of any fund than would be found m a 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 valu able for research, bui the use of this information in drawing generaliza tions is necessarily restricted. It is the obligation of both the investi gator and of those who read his report to make proper comparisons and to draw only ihoc conclusions which are valid and justified. A good slatnt.ill stucy o cases of cancer of the lung occurring 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, "or 0148 information from such a stuoy to be projected to some larger group, it is nicejiary that the autopsies represent 4 gooe samp.e of that larger group. To assume that such 1* the case in any particular icici 11 dangerous and likely to be false. There is some danger that the figures reported by some authors may be misconstrued as applying to asbestos workers or even asbestos miners, when, in fact, the authors in question do not make this generalisation, nor can the generalisation be made for the reasons stated. Close study of the reports reveals that the percentages quoted relate only to the group of autopsies covered by the-partic alar investiga tion. The present study, in contrast to the earlier works, has beer, planned to utilise the epidemiological method. A well-defined group of asbestos miners has been established m such a way that it constitutes a good sample of the whole population of asbestos miners m Quebec. Data (or all members of this group have been collected and analysed. Those concerning lung cancrr have received most careful consideration. De tails of the metbods employed will be set forth in a later section, but the type of approach is considered to permit of fair comparisons and valid gene ralisations. i e. IV. COLLECTION AZ ANALYSIS C: DATA A preliminary itrvey 0/ potential sources of information ,n February of la56 involved discussions with the physicians m charge ui the Asbestos companies' programs and with clinicians, pathologists, representatives of City and Provincial health departments and of the Canadian Cancer Society, aad other interested persons. It was tuund that morbidity data, although somewhat limited, were available iron such sources as the hospitals in Montreal and Quebec City, and the 11 Cancer Detection Centers in the Province, However, because qi the nigh mortality m lung cancer, it seemed advisable to depend upon .Lu relating to aeaths. These we found to be obtainable at the vital statistics department of the Ministry of Health in Quebec City. From the preliminary survey, it was apparent that extensive and detailed in* lorrr.ation could be gathered with respect to both the persons employed in the asbestos mining industry and mortality figures for the general population. Following this exploratory survey, the initial effort was iirectec to the collection of data relating to all workers who had been ;.rocv*seo tnrougr. the clinic at Tbetiord Mines since us inception m l'H?. Similar information was obtained regaromg all workers at the Canadian Johns-MinviUe Company in Asbestos. Data from the clinical records included the age, family and personal medical histones, smoking hub-.is, number of years of exposure, an estimate of weighted exposure, 0150 / Juki 19. nd the course 0/ the individual's health status or the cause cl his death. Al'.hcugh the data in these two instances were not exact!/ similar in form, the inclusion 0f records from the personnel department at Asbestos covering employees who had retired, died or become disabled provided data sufficiently alike for the purpose of the study. From this information it was possible to formulate for both Asbestos and Theiford Mines "cohorts" which could be well defined, should be representative of each group, and could be followed for adefinite period of time. All of the available experience indicates that the development of asbestosis in less than five years of exposure must be somewhat rare. Accordingly, the cohorts were defined as including every worker who had a total exposure of five or more years, and who was on the employment rolls at Asbestos or Thetford Mines in 1950. These cohorts were then followed by means of the annual physical ex amination records through a six-year interval, 1950 through 1955. All data regarding these groups were then tabulated in order to determine the characteristics of the cohorts. For those who survived the entire period, reference was made to the physical examination results and xray findings at the end of the period. Those who had died were tabulated separately and the cause of death corroborated by examination of the death certificates, A further search was made concerning those m the original cohorts who remained unaccounted for when the living and the known dead had been tabulated. They represent men who had left \ \ ,,inpioymeiu throw;.', retirement or resignation. Eventually, all but small number of there were accounted lor as either living or dead, jnd in the latter event, the caute of death was substantiated m a jur.iUr manner, and the results added to the original list of deaths. Death certificates for the Province of Quebec for the years 1452 to 1955, inclusive, were reviewed in the department of vital sta tistics of the Provincial Health Ministry, together with statistical sum ( maries of the causes of deaths in the Province by counties. All cases ia which death was certified as having been due to primary cancer of the lung were examined for such information as place-of residence, oc cupation, date of death, hospital in which death occurred, and whether ur no: an autopsy was performed. Cases in which ing cancer was given as a cause of death, but in which it was not specified as to whether the cancer originated m the lung, were also reviewco m an effort to in clude ail instances of primary carcinoma of the lung m the study. The statistics for the Province of Quebec relate to popula tion, total deaths from all causes, total deaths from cancer of all types, and deaths from lung cancer. These were collected and tabulated by counties and by sex for the years 1950 to 1955, inclusive. Prom them, death rates for the general population of Quebec and of individual coun ties were calculated for specific years and analysed by cause. Practically all employees of the Canadian Johns-Manville c Company are covered by a group policy of life insurance which, fortunately. 0152 21. nearly &11 of them continue to carry when they retire, A very few are not covered by this policy, ax.e tnose who leave the industry for ' one reason or another except retirement usually are no longer coverts, but this is likewise a small number. As an additional check upon the information obtained from the clinical records on the group at Asbestos, 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 workers were thus determined from the clinical records m the medical service of the industry and checked by means of the death certificates and insur ance company records. The list of deaths was then verified individually by reviewing them with the physicians in charge at Canadian Johns- Manvilie Company and at Thetford Mines. In this manner, 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 of death were considered separately. Mortality rates have been cal culated using both the "proved" and the total of "proved" and "suspected" cases during the years under observation. Comparisons were then made between the death rates tram the same cause among specific segments of unvxposed persons. All lung cancer deaths, both suspected and proved, were carefully analysed to determine possible relationship or corrslations oetwern the development of lung cancer and any factor known from the 0153 Zi. . ;.rlk; record* such as family history of tir.ct:, personal history .1 i.*'; smoking, coexistence o! asbestosis or exposure to asbestos. In addition to ibis analysis of deaths occurring in the co mets ana during the years under observation, every known death from , *ncer ot the lung, as well as every case diagnosed but still living, has bun tabulated and analysed. They will be discussed separately from those included tn the population and tiae.iaterval under study. A comparison of lung cancer mortality a the asbestoe pro* lucing counties has been made with that in counties which are far re* moved from the asbestos mats and in which, presumably, no asbestos miners live. Finally, a order to broaden the comparison of death rates m different population groups, the Tates have been collected for Canada generally, and lor the United States, according to the most recent pub* luhed and unpublished material. In order that the method by which these comparisons have mis mast may be more easily understood, it seems advisable to discuss briefly some of the fundamental statistical concepts which have been :otlowd. The principle of calculating the probability of a given sample representing the true condition of a large group can be illustrated by imagining a con tauter in which there are 1000 marbles of which 900 arc white and 100 black. The actual probability of drawing a black marble i> one in ten,or . 1. However, should a sample of ten marbles be drawn 0154 ::vm the container, it would not be unlikely that two, three, or ever, nu black marble* would be amur.g them, even though the "expected" numBtfr would be one. On the other hand, 1/ all ten were to be black, that fampie would unquestionably be "extraordinary". The following tabulation (how* a calculation of the probability that a given number ol black marbles will be found in a sample of ten: No. of Black Marbles in Sample _________ 0 1 2 3 4 $ 6 7 6 9 i Total Probability .3486784401 .3874204393 .1937102445 .0573?5o280 .0111602610 .0014880346 .0001377810 .0000087480 .0CCC003645 .0000000090 ,OOOCOOOOC1 1.0000000000 From these probabilities, it is evident that one might ex* pect a sample of ten to include no black marbles or one, two, or three, hut for the sample to consist entirely of black marbles would be ex pected only once ir. ten billion trials. Finding three black marbles in the sample would be expected in almost six samples out of 100, and it would be anticipated that the sample would contain four or more black 0155 / 24. marbles in slightly more than one trial out of ICO. The actual prob ability of this happening is .0l2?5184, which is determined by adding the probabilities (or 4 through 10. In practical applications of sam pling. the percentage of "black marbles" is, of course, unknown and must oc computed from the results found m the sample. There are limitaoons to the accuracy of such a computed value, but it is possible to state with a known probability that the true value lies within a certain range. If the range is wide enough, the probability say be practically 100%. The usual practice is to require 95% certainty. * \ In the present study, since the probability of having lung cancer is so small and since the sample sine was fairly large, the Poisson distribution was used instead of the binomial distribution, which has just been described. This is a substitution frequently made under these conditions, because the Poisson distribution is tabulated and the differences between it and the binomial distribution are quite small. It is based on the equation: -"P (no)X x1 Where e a 2. 7Ibid (the base of natural logarithms) n a number oi man years subject to risk p a incidence rate k a number of cases observed The logic of the statistical approach may also justify a few lures of clarification. Generally, in problems of this kind, one sets up s r.ypothcsis, which in our case would be, "Asbestos miners do not 0156 25. have * higher rite of mortality from lung cancer than the general popu lation." The hypothesis is then tested by meani of the study of data on > asbestos miners and on the general population, including the observed number of cases of lung cancer. From what has been said earlier, it ib clear that even if the asbestos miners and general population had ex actly the same lung cancer mortality rate, it is unlikley that in any single sample this identical rate would be found. Some difference is likely to be observed, but the important question is whether this differ ence is greater than might be expected merely as a matter of chance. In other words, we wish to know whether the difference is "statistically significant". If a sample should supply seven cases when the expected number (based on the rate for the general population) is five, one must inquire concerning the probability that this would occur purely as a matter of chance. It is this probability value which is calculated by the Poisson distribution. If, on this basis, a value is found in the sample which is so much larger than the expected value that it (or seme larger value) would occur less than 5% of the time by chance, there is sufficient evi dence to reject the original hypothesis. If, on the other hand, the value observed, even though larger than the expected value, is no greater than might occur by ch.r.ce in fewer than 5% of trials, we have insufficient evidence to reject the original hypothesis. Calculations and conclusions based on the results of the find ings in this study have been made in conformity with these statistical concepts. They will be presented in the following section. 0157 V. RESULTS AND INTERPRETATION Tbe rwo cohorts wtci were constructed aceordung to the criteria described in the preceding section have been considered in dividually and compared with each ether as well as with the general population. Description and comparison of these cohorts will be pre sented here as a preface to the results of the study. A tabulated summary of each group and of tbe combined cohorts is shown below: Asbestos Cohort Original Cohort im Lost Persons Deducted Pinal Cohort Living m 1955 (working and retired) 54 2273 2224 Dead by 1955 Ca. of lung Questionable Ca. of lung Other Causes Unknown Causes 49 3 0 46 0 Smoke rs N'ensmokcrs Unknown 1931 340 2 Thetford Mines' Cohort Summary of Combined Cohorts 3764 6091 79 133 3685 5958 3547 5771 138 6 3 123 6 2742 925 18 187 9 3 169 6 4673 1265 20 0158 t 27. Tab.cs 1,2, 3, and 4 present age. nurr.ser of /ear* e: cmplojwscn:, weighted average exposure ano smoking habits of these two groups. It will be observed from Table 1 that the Thetford Mines workers bad a higher average age than the Asbestos group (42 years vt. 39 years). Consistent with this finding. Table 2 indicates that they also had worked longer as asbestos miners (19 years as against 1$ years). A comparison of the exposure to asbestos dust is presented in Table 3. All workers were placed m one cf three categories, re - presenting increasing degrees of exposure based on a weighted average of the years spent at various levels of dustiness. The degree of dusti* ness for each job category was determined after consultation with per* sons familiar with the environment and conditions in the various work I areas. Although it will be noted that the two cohorts had the same average exposure, a larger percentage of the Thetford Mines workers will be found in category II, while the Asbestos group occupy mainly the extremes of exposure. Tor the purposes of calculation, the assumption has been made that the relationship between these categories is linear, and that category 12 is rwics as dusty, and category HI three times as dusty as category I. The fourth variable, smoking habits, was similarly tabulated end is shown in Table 4. A larger percentage of emokers is indicated here for the Asbeetos cohort - 83.0% compared with 74.4%. ) i 0159 2d. TABLE 1 Number ar.d Ferscr.:a;e Distribution ot Asbestos and Thetford Mine* Coaorta by Age Aabesto* Ae* No. 0f 20-44 ^54 5$-o4 65 UnJtnowa Totals av. Age 1602 44" 165 39 -22*5 19 Lea* than .5% 70 20 6 2 -100% The ti ora Mine* No. _% 2299 677 430 276 3 3665 42 62 18 12 8 -a 100% Combined No. _% 3901 66 1124 19 615 10 315 5 3a \ 5953 Too?. 41 TABLE 2 Number and Percentage Distribution of Aabestoa and Thetford Mines Cohorts by Length of Employment Length of Employ* ment Asbestos No. % 5* 880 .0-1# 864 20-29 342 JO-1* 168 40-49 17 50 * 2 Total* 2273 Av. Yra. of IS Eir.pl oyrr.e at 39 38 13 < 1 Too?. .ess than .5 % Thetford ___Mines No. ' % 915 1534 530 43S 168 53 3665 19 25 42 16 12 4 l 100% Combined No. % 1795 2398 922 603 185 55 5958 18 10 40 16 10 3 1 100*/- 0160 f Table 3 Number and Percentage Distribution of Asbestos and Thetford Mines Cohorts by Exposure Category Exposure C a t e: o r v A sbc s to s No. r* I 11 u: Unknown Totals Av. Exposure 969 564 735 5 2273 l. 9 Less than . s% 43 25 32 100% Tnet o r a M .ne s No. % 1062 1586 1037 0 3685 2.0 29 43 28 0 100% i i | TABLE 4 Number and Percentage Distribution o/ Asbestos and Thetford Mines Cohorts | by Smoking Habits Comb::r.ec No. r' 2031 2150 1772 5 5958 2. 0 34 36 30 "icc% j Smoking Habits A shestos No. % 1 Smokers 1931 85 Nonsmokers 340 15 Unknown 2 Toieil g 2273 100% Less than . 5 % Thetforo Mines No. r 2742 925 18 3685 74 25 I 100% Comb i?.e No. r/O 4673 1265 20 5958 79 21 Too% ( 0161 JO. Thu i* a difference which could hardly occur by chance because of ite Urge me o: tie sample. Therefore, it is likely that the eifierence is a real one unless the method of recording this information at the tune of employment varies at the two. locations. In spite of the minor differences brought out by these comparisons, it would seem that the two cohorts are quite similar with regard to the variables of age, length of employment, degree of exposure ana, although less so, in regard to smoking habits. These variables appear to us to be those most closely related to the problem, and will be taken into account in comparing the workers. with the con trol groups. Table 5 presents the year-by-year experience of the two conorts ann indicates the 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 beer supported by an autopsy or surgical resection of the lung with microscopx examination of the removed tissue. In one case so considerec, however, diagnosis was confirmed by bronchoscopy with visuaii latior. and biopsy, in another, although there was no autopsy, the diag nosis of primary cancer of the lur.g seems to have been beyond question. The term "suspected" primary cancer of the lung was ap plied to those cases m which the aiagnons remains m doubt but some of the evidence points to cancer of the lung. There were three such cases. Study 31 '.he Asoenss Canor: No. Alive At Beginning Year oi Year Cause of Proves Suspectec Primary Primary Ca.of Du.-.? Ca. of Lung Death Other Causes ManYears of Unknown Ris< 1950 2271 1951 2267 1952 2261 1951 2252 1954 2241 1955 2211 Totals 0 1 0 0 0 2 1 0 6 0 2270 0 5 0 2264 0 9 0 2256.5 0 9 0 2247. 5 0 12 0 2217 0 5 0 222'.5 0 46 0 11502.5 "Proved" cancer of lung death rate per 100, 000 man-years of risk * "2 'mil.!1 TABL 5 - Part U Stu2y of the Toe tier a Mines Cohort No. Alive At Beginning Year of Year Cause of Provee Suspectea Primary Primary Ca. of Dung Ca. of Lung Death Other Causes MinYears of Unknown Risk 1950 3665 1951 3615 1952 3661 1951 3611 1954 3605 1955 3579 Totals 1 1 0 2 l 1 & 2 6 1 3680 0 12 1 3668 0 28 0 3647 1 25 0 3619 0 21 4 3592 0 31 0 1563 3 123 6 2 1 7o9 "Proved" cancer of lung death rate per 100,000 man- /ears of risk * 27 'life1 "Suspected" plus proved cancer of lung death rate per 100, 000 man- years of risk 41. 3 ( - ) 21769 0163 32. TABLE 5 - Part Ui Stubv o: Combines Conor:* Corr.binea eeath rate* per 100,000 mu-^ciri of risk ___________for Asbestos ar.d Thetford Muses 'Proved" cancer of lung death race per 100, 000 man-years of risk * 9 2S.5 (35 271.5r) "Suspected" plus proved cancer of lung death rate per 100, 000 man* 12 years of risk 34. 0 ( 35271.5 In two, no autopsy was performed but tbe cluucai signs ash symptoms were such that the death certificates read ''cancer of the lung", and "suspected lung cancer". The third case carat to autops/ but there was a difference of opinion between two pathologists as to wbetner lung cancer was present. The ten.: "man-years of risk" has been used to mean the number of men at risk for the year under observation. An individual who lived throughout tbe 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 these two cohorts, and in which lung cancer :* consioered to save been proved as a cause, are shown in tabulated form on the nest page. Also shown are three deaths in the Thetlord Mines cohort which have been considered as "suspected" lung cancer cases. 0164 33. ASBESTOS COHO,?? "Proved" Cases of Prtrr.ary Cancer of the Lung Narr.e til Smoke r Exposure Died l. A. J. 66 Ves 26 Yrs. tn Cat. 11 10-12-51 1. N. P. 65 Yes 34 Yrs. in Cat. 1 S- 3-55 J. R. M. 65 Yes 37 Yrs. in Cat. 1 7.20*55 An- Aftbtstops v tons Yes Yes Yes No No No THETFORD MINES COHORT "Proved" Cases of Primary Cancer of the.Lung Name A^e Smoke r .\ o o $ l r e Died Au Assestop ) v tons 1. C. B. 2. A. S. 3. W. F. 4. L. D. 5. E. L. 6. A. R. 59 48 61 56 37 68 Yes Yes Yes Yes Yes Yes 32 Yrs. tn Cat22 Yrs. in Cat. 33 Yrs. in Cat. 30 Yrs. m Cat. 16 Yrs. in Cat. 28 Yrs. in Cat. 1 8-20.50 II -.51 Ill 4-30.53 U 11-22-53 1 8- 5-54 Ill 5- -55 Yes Yes Yes Yes Yes Bronch.. No Yes Yes Yes No No "Suspected" Primary Cancer of the Lung Name tn Smoker Exoesure Died 1. J. T. :. r. d. 3. P. V. 49 46 5 Yes 32 Yrs. in Cat. Ill 10-25-50 Yes 33 Yrs. in Cat. 111 7- -53 Yes 42 Yrs. in Cat. 11 9-30-55 Au- Atbei toes v tosis No No Yes Yes No No 0165 ( 34. At Asbestos there were no cases m w-.irh t.-.e ji qucsticr.acie, with the result that the rate ter "prove: ' esses this conort is the only one developed. At Thetford Mines, r.owever, the three eeses mentioned earlier were pieced m the category si "suspected" primary cer.cer of the lung. An indication of the u-nportencc of these ceses in interpreting the results of the celculetions is desireblc before further discussion of the mortality retes which ere derived is leter tables. Tor example, it happens that the rate found for the Asbestos cohort is very close to the "expected" rate based or. the general population figures' for the Province as will be shown later, and on this basis, we should find five deaths from lung cancer among the Tbetford Mines group. As was explained is the section on "Col lection and Analysis of Data", it would then not be uniilccly for six cases to occur in our sample. This is, in fact, the number of "proved" cases found in the Tbetford Mines cohort. If, however, the three additional "suspected" cases are included, increasing this figure to nine, the whole situation changes from a statistical point of vtew. Since the 95 level of probability is this case falls between 9 and 10, we would reject the Hypothesis that there is no difference between the incidence of lung cancer in miners and that in the general population if we found ten or more cases. On the other band, having found nine cases we are not above the vS? level and are not justified in rejecting the hypothesis. Nevertheless, the occurrence of nine cases ir. this sample would show 0166 r 3S. an increase :r. n'c apprcacr.es :.*.c s .g-... .car.: .c.-v... Seca-sc of tn tremer.eous importance o: the ^uestie.-.aO.c cases in this res pect, *ome detail regarding them wii; be given here. in or.e of these cases, the suspicion of cancer of the long is based uper. 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, es c pecially if a localised censity or a superimposed tuberculous lesion is present, can simulate that of a tumor, and by itself,, does not justify the inclusion of this case as one of "proved" cancer of the lung. A second case was certified as having died by reason of hydrothorax, possibly due to lung cancer, but again there was no surgery and r.o post-mortem examination. In the third case, although it was sub.ectec to autopsy, two pathologists disagreed as to whether lung cancer was pre sent. The death was certified as having been due to chronic myocarditis with nephritis aAdpulmonary congestion, and possibly cancer of the lung. On the basis of these facts, it seems unwarranted to include these three cases among "proved" instances of lung cancer. On the other hand, they cannot, in fairness, be sisregarded completely. It is for this reason :aa: mortal.:'.' rates for the Thetiord Mines cor.cn ana the comomec coI I hort have been calculated both ways. Table 6, giving the rates by age groups, reveals different experiences for the two cohorts. It happens that all of the deaths in the 0167 Asbestos eor.or: fail into one age grou;>, so that tne rate tor tr.it age cate.or. ;s exe ep tiena.i y r.tgn. A: T'ct.orc .'.'..no, a more e-.cr. e.st.-:bution ot tr.e ctit.n by age deveiepee a eerie* of rates which are Ie extraordinary and, as wif; be *eer., are not widely divergent from the expected rate* for each age category. The unu*uai rate in the Asbestos eonort for tne age group 65 years and over, is the sort of thing which happens wner. the sample is small. Tor example, of tnese tnrte deaths, two were exactly o5 years of age and would have been in anotner age group bad the limits been increased by one year. TaBLZ 6 N.rr.ser z: ?erso.-.s u: S_-=oer z: - 1 L--ng Cancer Ccatos sv Age Gro.ps Age Cro.ss Asoe'stos L -i Cance r Persons Seat*.i Thetf ere Mines Combined Lung Cause er Lung Cauictr Deaths Deaths Pe r s or. s Prove; Toil. Persons r?:vet 7 c:o 45-54 55-64 5Ci./stsa r. a> * . ; oc: 4-s: 155 Js '> 22* i . o 0 0 3 0 3 22 = 9 1 1 5901 i 677 1 3 1124 i 430 3 3 615 3 276 1 2 ) 00 315 4 30 3:^3 6 5 5t:6 ; i 3 3 5 0 5 ___g______ , it 1 1 3 tr.ioown Over -ail No one exposed - 0 0 1292 t 72 --* f , f t 0 ' t . * - 25 74 116 116 60 121 00 T? 41 *._. r *: t *. . 1 * w 4 :s 61 212 0 IT S 44 81 265 0 34 0168 37. The risci by ieng:r. ol emplovn-.e n: (T. u. * 7) ).: :ne two group* r qu.:e stm.ia.- this respect. During the tin: <0 years ol eroplO)*ment, the rate rises, an observation wtich seems plausible since the men were growing older. However, alter 40 years ol exposure toere are no "proved" cases reported lor a total ol 240 men curing the six years, or about 14-40 man-years ol exposure. When the "suspected" cases are added, one case does show up in this period. This would produce a rate ol 69 per 100,000, again demonstrating the importance ol these questionable but unproved cases to the linal con clusion, because, u there were no cases in this number ol men with tur-.g exposure, and il asbestos is a carcinogenic agent, it must be con cluded that these 240 men have demonstrated considerable resistance. This is a biological phenomenon which has been observed previously ar.s is consisted with the theory ol sn intrinsic or endogenous lactor ui can cer. The only other explanation would be that the susceptible members el this age group had died earlier ol lung cancer. Table 22 which ap pears later in this section iscicstes that the members ol the cohorts did no^dte Irom lung cancer at a younger age than the general population. The rates by wcighieo exposure are shown in Table 8, and t :l! be r.utec that they present strong evidence against asbestos being a carcinogenic agent. For the Asbestos cohort the rates actually de crease with increasing degree ol exposure, and at Thctlord Mines they sppear completely uteependent of exposure, il we count only the "proved" f // k \ \ \ U wul be notec from. the tabic that the mortality rate for the Asbestci cohort is almost exactly the same as that 'or the Province, r.tir toe rate for "proves" cases m the Tbetford Mines cohort is eniy slightly higher. When the "suspected" cases are included in the calculation, the rates for the Thetford Mines cohort rises to 41.4 per 100, 000 which ( is nearly twice as high as the rate for the Province. This, it will be recalled from the previous discussion of the "suspected" cases, ap proaches but docs not exceed the significant level. One further interesting observation from Vabie 20 is the rather marked increase in the total number of cases for the Province between l?50 end 1955. It is assumed that at least part of this increase is due to improvec recognition and reporting of lung cancer during the interval. Por this reason, the years 1954 and 1955 were thought to be more nearly representative of actual conditions. ven so, it is quite likely that the general population is not studied for lung cancer with the same diligence with which this disease is looked for in the miners, and it seems probable that the mortality rates for the Province would tend to be low. This *o\ud appear to be substantiated by the fact that the reporting ai cases m the combmeo cohort showed no such ir.creaie over the same period. Table 21 was compiled to show the annual age>spccific ,ung cancer rate of cases in which the death certificate merely read "cancer of the lung", as distinguished from, those in which the diagnosis was 01SS Number of Person! anc Number of Lung Cancer Deaths by Length of Employment Length Asbestos Thetfcrd Mires Combined o( Lur.* Lung Cancer Lung Cancer employ Cancer Deaths Deaths ment Persons Ceatns Persons Provec Teia. Persons Proves Iota. o- o1 5-9 l0- 19 20-2 40-4c sC* Totai 8S0 864 342 168 IT 2 7TT3 0 915 0 1534 l 58C 2 435 0 168 0 53 T Jm5 0 1 2 3 0 0 6 0 1795 0 0 1 2398 1 1 2 922 3 3 5 603 5 7 1 185 0 1 0 55 0 0 9 595a 9 77 Annual Lung Cancer Death nates pt 7 lGv , ,*',<V-<*-> Man-Years oi Ejtposur c by Length of Employment Length of Emptovmer.t 5-9 10-19 20-2 30-30 40-40 so* Over-all Asbestos Total 0 0 49 198 0 _0 22 Thetsord Mtnes Pr oveo Iota. 00 11 11 57 57 115 192 0 99 0 _0 27 41 Combi r.ed P*oveo Tot*. 00 77 54 54 138 193 0 90 00 25 34 0170 3. 7A3- 6 Number of Persons and Number s', Lur.j Cancer Deaths by Exposure Category Expos urc Categorv Asv S'.OS The: ford V.tnes Combtr. ec Lung Cancer Lung Cancer Cancer Deaths Deaths Per sons Deaths Per sons Pro ved Total Per sons P:eves To:*. 1 969 2 1062 2 2 2031 4 4 12 564 1 1586 2 3 2150 3 4 112 735 0 1037 2 4 1772 2 4 UnJeiows 5 0 00 0 30 0 Total 2273 3 3665 6 9 5956 9 12 Annual Lung Cancer Death Rates per 1C0.0CC Man-Years o/ Exposure by Exposure Category Exposure Catecorv Asbestos Total 1 12 122 Ualoiown Over-all 34 30 0 0 22 No one exposed Tnciforc Mines Prcveo Tota. 31 31 21 32 32 64 0 27 41 Comb: r.ed Provec To:i. 33 33 23 31 19 37 00 25 34 0171 - c. ;; espoiure to assestos is in any *> eonr.cetcs to lung cancer, we wouio xpxctbit tbc longer ane heavier ebe exposure. tbe higher the rate that would be foune. The only possible error m this interprets* non could occur li the weighted exposures were inversely related to years of employment, :n which case the heaviest weighted exposure (category HI) would show tbe shortest length of employment. Tables 9, 10, and 11 which list tbe number of persona in various exposure categories by length of employment indicate that this error has not occurred. In fact, the average number of years of employment for each exposure category is almost identical. TABLE 9 Number o: Persons in Various Weightec Exposure Categories by Length of Employment Asbestos Length of CRioiO'.Tr.er.t 5-9 :o-: JO-29 >040-4^ 90 Total Av. Yrs. of Lapcsurc Weighted Emcsure Catercnes I 11 ill 428 273 159 98 9 ___ 2 969 15.5 213 217 89 42 3 ___ 0 5o-4 15.2 239 373 92 27 4 ___ 0 735 14.5 Unknown 0 1 2 l 1 ' 5 29. 0 Total 180 864 342 163 17 2 2273 IS. 1 0172  / \ 4* ABLE 10 Number o.' Periom ir. Venous W'ejghtec Exposure Categories by Length 01 Employment Thetlord Mines 'Length ol Emplovment Weighted Exposure Cetegortrs _1_ Mi Unknown Totel 5-9 279 385 251 0 915 10-19 390 666 478 0 1534 ( 20-29 30-19 155 274 151 149 176 110 0 580 0 435 40-99 67 64 37 0 168 50 * 22 21 10 0 53 Totei 1062 1 56o 1037 _ '0 3665 Av. Yrs. ol 19. 9 18.7 18. 1 18. 9 Exposure ; TABLE 11 J Number ol Perioss in Venous Weighted 1 Exposure Categories by Length ol Employment \ Combined Asbestos end Thetiord Mines i -------------------------------------------------------------------------------- i L__e_n_g_th o.l .W...e..ig..h..!.:.t..i- Exposure C__e_t_e_:o_r-.es Emolo^mcnt -i- _U 1U Unknown Totel 5-9 707 593 490 0 1795 10-19 663 833 851 1 2398 20-29 314 363 243 2 922 10-3 24* 213 117 l 603 40-4? 76 67 41 1 135 50 24 21 I 0 _0_ 55 Totel 2031 2150 1772 5 5958 c A. Yrs. ol Exposure 17.8 17. 8 16.6 29. 0 17.5 Table 12, whjcb develops the rates lor smokers and nonsmokers, it most striking. It shows that no: a s.r.g.c case of _r. g cancer developed among the 1265 nonsmokers ana that all cases of lung cancer, both "proved" and "suspected", occurred m smokers. A comparison of Tables 8 and 12 certainly suggests that smoking is a greater haiard than exposure to asbestos in the mining operations. Table 12 was so striking that it was felt that further verification was accessary. It was possible that some abnormal distri bution may have occurred, c.g., the nonsmokers may have included a larger percentage of young men. Consequently, additional Tables, 12, 14, and IS were constructed to show the distribution of smokers and nonsmokers by age, length of employment, 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 lest than that of the nonsmokers. Table 14 shows that as far as length of employmeat is concernee, the smokers had worked about 2.3 years less on the average than tbe nonsmokers. With longer exposure and greater age, one would expect the nonsmoking group to show a higher rale if lung cancer were due to asbestos. Table 15 shows that the average exposure category was al most the same for tbe two groups. Therefore, ibis variable seems to be of no importance in accounting for the difference between lung cancer dcatb rates for smokers and nonsmokers. 0174 TABLE 12 Number of Persons and Number of Lung Caaeer Deaths by Smoking Habits ___jAsbestos^__ Tbetford Mines Combined Lung Lung Cancer Lung Cancer Cancer Deaths Deaths Persons Deaths Persons Proved Total Persons P.-ovea Total Smokers Nonsmokers Unknown Total 1931 340 ___2 227 3 3 0 0 "5 2742 925 IS 3685 6 0 0 6 9 4673 9 12 0 1265 0 0 0 . 20 0 0 ?-' 595S 9 12 Annual Lung Cancer Death Rates per 100,000 Man* Years of Exposure by Smoking Habits Smokers Nonsmokers Unknown Overtoil Asbestos Tota. 26 0 0 22 Thetford Mines Provea Total 36 55 00 00 IT 41 Combined Provec Tota, 32 43 00 00 25 34 0175 f K t e c c$ P5 ^ * * |C *- a e9 C >* A o e o Z < f n9 ; d|2 =^ Xd <NM NO J* O-- j Cx" -- -- j'fi e* i lb-- o 2 oIt sr r ^ -- 9 x -- n -- o tf' f e* x ff* X^ X ** ** X N T :$ (0 -- -- e e l~ o o te V _5 jot I|t t*/> *** o' z9 -- -- ^ o o -- >r Om ^** O ** ^9 9 c! * * - /^sc a. Jlc , 9 Cl 0 0 ow o siz i u v IT N S / c e* x ic > *- - 3 A. I K 0 ic eM o Z c9 0 _ * e <c x --...^.................S. H|CC X---- *--^^ o X C C* X o _ _ o * -* jk* tEo f-* & > V x-- I-- c eeoc 9 } e a 2 xw C2 Z: <c o ^ r* * * 1tS e ?* -- r 0176 4 45. c v c > e Q. % 2 0 9 JCfa a1 C h< oe Z o cm J c z ' O r *4 o e -4 * i s 2 1 : r *4 e* -- 49 kfTa i 2 m T - r O -- -M f*N Xk o ** m C 9. e JS Ie s* m o c2 4 * *4 mm T 1*4 * 1 *4 *4 kfaT. c* #4 Z * 0 "a. E U! *< 0 X # e t J w X i. V X 0 c >1 e e Z c E (A ac s <e JO #4 " *4 4* * i*4 4T e* mm m *4 f*a #4 OD -- if - - o t*. e X e * . %t X 0 E V) faa 0 1z s, .V JK Wmm* mfma *e4 Oo eo j J5 u M .5 e*4 * C* 9r *4 _ r r -- r* -- x > d l f * 0.5 i* k tf *e *4 O * r e m k9T 2 H 6 V J mm 1 s * 4 u >^ c <a u Vc Vfa 41 ., = l[ D C2 l xl o a a c S ]'- *c fsa * fa. - X* C9 gZ 0 E j * -I-1- U fa fa X -- -- ^ *.* . r f*.1| 0 O N / ?* N 1 g <5 94 e > e0 O f* ex -- V *X e fa 2 fa 0 mm i C c z a X 2 e *4 m -- . --i/i m .1: ** , fa X fa H &> X 9 /i C ^ - mfa c i | tr o* X ee e 1i fa 0 n o o fa X 2 kT ^ ^ ^ 4^-> - ji t M Z n: < fa fa X 0 * S * to o ue* ^0 jr -5 ^ f_* c" *rg ^> .2 4 *-- Xi " 94 0 0 *f* O' 0177 V 46 z: *: -- r C I'M c ` '* ; -? 1 Ss 3* j!^ -^* * -- o<xM- y. 2 si X fft. . If' :9 X A | 2 = <i 0 U 3 SC X uV 0 x X ^ ^ *4 ^ % 'Si U C r 3 J e " r> o[ i *9 3 e N^ - O9 o a K Ul e ^ e e > ^3^0 3 6 ^X Cm A 4! * < b o Z xc * it A 0 <* N N O / P 3 e -- ^ * "i ^ ** A| C* -- i -- r e r* : ) -- -- e I** je o 4 *4 ^9 E e e-- Z' c X 9 Z e v'_ o * Oj* JS , . . . . I * * jo v E h ^ ^ *" V) 1 JC c e : IS t 2 o' e xx in 9 3 5 lx * o 2 S|" u v AC 5 ^ Z *o v lx x 3 9 s9 *C z? it , tt o o' *^ .e *N X ` 9 l| *9 43 `J i. r ,3 9 ^ * j :* * 3< -J u *. --J * Sj 5 i 0178 4:. The remit of this adeuiona) snajvi.s i that none af these factors appear to lessen the effect of Table 12, which is therefore strongly suggestive of the importance of smoking as compared to the other variables. Ashe stasis and i-u-.; Cancer When we attempt to relate the lung cancer deaths occurring in the cohort with the reported cases of asbestosis, we ere immediately aware of a disturbing inconsistency. Various authors report the incidence of asbestosis after 10 or 15 years of exposure as exceeding 50%, and in one study, as high as 6*%. However, data or. cases of asbestosis from the cohorts at Thetford Mines and Asbestos pro duce a rate of only about 5%. It is true that these data are based on only those esses which have been proved at autopsy, and those whose most re cent x-ray interpretation resulted in a diagnosis of asbestosis. This in cidence may be far lower than if based on microscopic examination of the Jung tissue. As a matter of fact. Dr. Cartier has estimated that there are probably 300 workers who do not show radiological evidence of asbestosis, hut who have some degree of fibrosis. He also estimates that there arc perhaps 40 workers who may have died or retired with this disease. Instead of 143 cases of asoestosis in the whole working force at Thetford Mines, we should then have perhaps 500, but even this would result m an over-all rate of less than 10%, which is far below those widely reported. In our 0179 48. combined eor.ort, there ire 1 765 men who have bid more than yearsjf employment, and 431 of the** hive worked in the heavies: average exposure. According to the records, we can account for only 138 esses of asbestosis in the combined cohorts. If even 35% of the workers with more than 20 years'exposure develop asbestosis, we should expect about 425 cases. This leads us to believe that there is a very considerable under-reporting of asbestosis. Such a hypothe sis is easily conceivable when one considers that many chest x-rays in thus group may be considered normal by comparison with others in the same group whereas, if they were to be compared with what are considered as normal chest x-rays elsewhere, they may be inter preted a* showing fibrosis. Case* of asbestosis which were accumulated from the autopsy records and from the periodical physical examinations result m a distribution which is shown in Table 16. TABL 16 Distribution of Recorded Asbestosis Cases In Cohurt Living Deao Total Asbestos 18 4 22 Thctlord 86 30 116 Combined 104 34 138 0180 *! ---- \ A <5. TABLE IT- Pa.-ti Nusober of Asbestos.* Cases By Length of Employment ana Exposure Category Asbestos .Length of Emolovraeat Leas than 10 10-19 20-29 30-39 40-49 50 Total Av. Yrs. of Employment Exposure Cate* or v JL_ HI 00 01 27 01 00 00 29 25 25 0 2 4 4 1 0 11 29 L'njc-.owr. 0 0 0 0 0 0 0 Total 0 3 13 5 1 0 22 2T Percentages of Asbcstosis Cases By Length of Employment ar.c Exposure Category Length of Emnlovrr.en: Exposure Catesorv 1 U 111 Less than 10 10-19 20-29 30-39 40-4<> 50 Over-at; 00 0 0 .5 .5 1.3 7.9 4.3 0 2.4 14.8 0 0 25.0 0 .2 1.6 1.5 No one expose z -z :ais gro-p Un.known 0 0 0 0 9 T Total 0 .3 3.8 3.0 5. o 0 1.0 0181 so. Number of Asbestosis Cajcs By Length of m.p;9ymen( and Exposure Category Thetforc Mines Length of Err.olovmer.t Le s * than 10 10-19 20-29 30-39 40-49 so Total Av. Yrs. of Employer, er.t ZLxoosure CiK^orv IT 00 01 2s 2 15 06 02 4 29 30 36 0 7 21 33 20 2 63 34 UnJciowr. Total 00 08 0 28 0 50 0 26 04 "0 11 6 34 Percentage! of Asbestos:* Cases B y Length of Employs'ent anc Exposure Ca legcry Length of Emalovner.t Exposure Cat eror v U in Lets than 10 10-19 20-29 30-3? 40-49 50 Over-all 0 0 1.3 1.3 0 0 .4 0 .2 1.8 8.S 9.4 9.5 1.8 0 1.5 13.9 30.0 54.1 20.0 6. 0 * No or.e exposed in this group Unknown 0 0 0 0 0 Total 0 .5 4.8 11.5 IS. 5 T.S 3. 1 0182 ( e 51. TABLE IT -Part Id Number oi Aibit'.siii Cim By Length of Employment end Exposure Category Asbestos uc Thetford Mines Combined Length of EnsioiT.er.t Lee* than 1 0 10-J? 20-29 30-39 40-49 50 Toul Av. Yr*. of Employment Ewosure Cat C90TV i n_ 111 000 029 4 12 25 2 16 37 0 6 21 022 6 38 94 2S 33 33 Unknown 0 0 0 0 0 0 o; Tou: 0 11 41 55 27 4 138 33 Percentages of Asbestosis Cases By Length of Employment ar.c Exposure Category Length of Emolovmer.t Exposure Catet; orv Id Less than 10 0 0 0 10-19 0 .2 1.0 20-29 1.3 3. 3 10. 3 30-39 40-44 .8 7.3 27.0 0 9. 0 51.2 50 * 0 . 3 20. 0 Over-all . 3 1.8 5. 3 ned in this group Unknown 0 0 0 0 "o Total 0 .5 4. 4 9. 1 14.6 7. 3 2.0 0183 5:. A percentage i.-.eider.ee of asbestosis :er t *c exposure ciujcrv uj deed ceve.cpec as well as for each perioe c; emp.sy- mcat. Thu uu'oraiuen is shown in Table 17. It will be notec tbit within, an exposure category, the incidence rises with increased length oi employment. 1: is > apparest tbit the incidences, even m the category of heaviest ex* posure, arc far below the rates found by tbe authors previously re* r /erred to. It secras clear, that unless concentrations of asbestos dust to which tbe miners are exposed are very much lower thaa those wh.eh ootaia in all tbe other stuctcs, there has been a*gross uacer. reporting of tbe asbestosis cases. The obvious result is a higher relative frequency of luag cancer la association with asbestosis. Table 18 compares deaths due to luag cancer and fatal cases with as* bcstoais, alone and m combination with each other. TAB LX 18 - Part 1 Statistical Analysis of the Causes of Death Asbestos Cause Asbestosis No Asbestosis Total Percer.taje Lung Cancer 1 ( .2) 2 ( 2. S) 1 6. 1 No Lung Cancer Total 7 0(42.2) 16 93.9 48 49 Percentage 8.2 91.8 Figures m parenthesis arc the 'expected*' number S . 0184 Tab -Z i 8 - Pi Statistical Analysis oi lie Causes ct Ztut. Thetford Mine s Cause Asbestosis No A sbe si is ;s Total Perecntiee Lung Cancer No Lung Cancer Total Percentage 3 ( 1.3) _25 (26.7) 38 31.3 3 ( 4.7) 101(99. 3) 104 78.8 6 136 133 4.3 95.3 figures in parenthesis arc the "expected" numbers TABLE 18 . Part HI C Statistical Analysis of the Causes oi Death Asbestos and Thetford Mines Combined Cause Asbestosis No Asbestos:! Total Percentage Long Cancer No Lung Cancer Total Percentage 4 { 1.6) 38 (30.4) 33 17.7 5 { 7.4) 144 (141.6) 149 83.3 9 172 181 5.0 95.0 Figures in parenthesis are the "expected" numbers Six deaths from unknown causes not included The number of lung cancer deaths combined with asbestosis is larger than would be expected in each cohort and m the combined cohorts. Thit difference is significant at the $3% level using the chi* square test of significance. The importance of the under-reporting of asbestosis can be observed in Table 19 0165 Statistical Analysis o: the Causes of Death if 20 Nonasbestosis Cases baa been Diagnosed as Asbestosis Cases Cause Asbestosis No Asbestosis Total Percentage Lung Cancer No Lung Caacer Total Percentage 4( 2.6) 48(49.4) 52 23.7 5 ( 6.4) _14{122.6) 129 71.3 9 rT2 181 5.0 95.0 Figures in parenthesis are the "expected" tuuabers la this table, it has been assumed that 20 of the cases which dab not have lung caacer and which were reported to have no asbestosis did, in fact, have asbestosis, the diagnosis of which was missed. Althouga the cases of luag caacer with asbestosis are still higher than would be expected, the difference is no longer significant at the 95 level. This still is true if fewer than 20 cases were shifted but it is reasonable to expect that at least 20 of the 144 might have shown asbestosis bad they been subject to autopsy. On the other hand, a shift of about 40 cases would produce an expected rate almost equal to the rate found. Explanation of this effect of under'reporting of as* bestosis has been strctsca because it seems so obvious that in under reporting asbestosis the relationsmp between it and lung cancer has been made to appear more significant than it probably is.  1 i it . I : 55 Tour of the proved cases of lur.g cancer arc see of :he suspectec were associates with asbestssis. Since we nave er_y 12 deaths is which asbestos;* was present according to the r*cores, the incidence ui this series is 12.5%. wniie this is sligr.nl/ lower than the rates foe -.d by Merewetber, Cloync, and Wcdler, it is still l much higher than could be expected if the asbestosis incidence were anywhere near the experience reported by other authors. c* Corr.sanson of the Cohort xserience with that of the Province of Quebec, Qon:union oi Canaca. ane tne Unites State* > la order to make a comparison of the experience am.or.g , 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 Provinciai Ministry of Health. The I data on total deaths, deaths from all forms of cancer, and deaths from 1 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 examined for the years 1952 through 1955. Table 20 gives a tabulation of the number of deans from lung cancer in the Province aao in the two cohorts for the years 1950 through 1955, and shows the annual rate per 100,000 in these segments. 0187 c 0189 f *\ A p p ro itlm a tc m id -p o in t of the e n u m e ra te d p o p u la tio n fo r 1951, and the e s tim a te d p o p u la tio n fo r I^S 4 . |fla p | o rt, l)lv . de la D e m o g rjp lile ) 58. confirmee by autopsy, surgery, or biopsy. The terra "spcc-iiec primary" refers to those ctiei is these same two categories is which the rumor s specified as having origisatec is the lung. It will be noted that, of tte total cases certified is 1155, a much higher percentage than is 1984 was specified as primary. The tabic also shows that a higher percentage ef the total, cases certified in 1958 were proved, agais indicating increasing interest in this disease, A comparison has been made between the age-specific rates shown m Table 21, and those for the cohort shewn is Table 6. An average of the 1954 and 1955 rates for the Province has been used, since the 1955 figure was higher and may have been exceptional. This comparison, summarised is Table i2, shows that the observed number of deaths is our sample is not significastlv greater than the cxpectco number of deaths, based on the average of the 1954 and 1955 figures for the Province. It is true that, is the case of the age group of 85 and over, the five deaths provide a figure which is al most significant at the 95% level. However, it should be noted that this numbi-r includes one of the suspected but unproved cases previously referred to. furthermore, it is rather likely that the rate for the gen eral population is uaoerstated is this age group, tor the obvious reason that the exact cause of death in the very old is net a matter of the same intensity of interest as it is is younger persons. 0190 \ \ \ 59. Before leaver.; this comparison of the Province with `.fie miners, it should be shown that their age distributions ere reasonably the limt, Thst this is the case car. be observed from the following tabulation: Age Distribution of Adult Males for the Province of Quebec, 1951 (Rapport, 1954) ( Percentage Age Crous Number Percentage Combined Cohorts 20*44 45*54 55*64 65 v Total 727, 135 188,952 128, 944 113,467 1,153,498 63 : 66 16 19 11 10 10 5 100 100 It should be remembered that the miners retire anc con sequently, it can be expected that the oldest age group will be larger in the general population. The data presented in Table 23 indicates *?. that the lung cancer rate generally decreases after age 70, and we m*'' could expect the rate for all people over 65 would be smaller than the rate for a group of 65 to 75, which would apply to the oldest group of miners. It is felt that by using the whole adult male population, we have developed rates which are somewhat lower than if we had been able to exclude the general population over 75. 0191 S4 ** Nsj T1 fat f g* 6 g * x xi--1 -^ T t/T C. x a a >* -- x t-* o V 2 E *4 a <m > *4 i "i fa 9 O -- zl CX "> i ew 'r - a- 5 ** M Xw i! - X =< . -3 x0 v 2 * k2 vx W ew y u c 3 ^ x-- r3 ^9 u */> * * I i/i ^ Z' W* O'*1 O r^ In & 3 0tut 9 "V9 >fa C2 c *4 <m ** r'f *11 *> r* * 1 -- X* X X( w j: 92 X 9 fa S3 X 9fba fa X _ 41 ** > tf ^-- x ** *f*ati*j -- tv x a -ir -|l u 7? e-- *Te i *k .*3> x X9 < iy *g * ji -- r -- <r*4 X *- e o .fa V 0 f fa *9 X X fa W-- 9c Q a to <1 4> uc X Ux . 9 -) *t r <* [x *j ^ X faJi*- jo ce i *jfx-- >3>J* N^ S e c < *: J 1. s oc ae o:iIo **** 14 X -* *X c.^ o" &w u 0 m a 2] 32 c X- Xx x 9 U < I a x x w* 9 n frfi o r x* x _ 5 9 V x* x* x Xi ^ x C < 0192 e.. table 2: Comparison of she Actual and Expected Number of Lung Cancer Deaths by Age Among Asbestos Miners Age Crouo Province Toul Specified Primary Rate oer 100, 000 No. of M .ne r s Expected* No. of Deaths Observed No. of Deaths Prcvec Total 20-44 45-54 55-64 65 4 Unknown 1.8 24.5 67.6 89.3 -- 3901 0 1 1 1124 2 13 615 2 33 315 2 45 3 00 * Actually . 4 The expected number is based cr. she average of the 1954 and 1955 age-speciiic rates for the Province of Quebec. Table 22 also answers a question previously raised. It shows that the members of these cocorts have not died from lung can* eer at as age earlier than the general population, and that such as ex* planatioa cannot be offered for the absence of lung cancer is 240 men with.more than 40 years of employment referred to on page 37. A comparison between the asbeitos miners and the popu lation of the Dominion as a whole was made, using statistical material from several sources. In one eource, Phillips ^ ^ gave age* and sex* specific rates for Canada for three periods between 1931 and 1952. The rates for males are given m Table 23. 0193 -T , - -| --< 62. TA3 2.Z 23 Annual Death Rates per 100,000 lor Cancer of the i-ung in Canada* Age Crouos Under 30 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80.84 85 AU Ages 1931-1933 0.2 0. 9 2.0 3.0 5.2 8.2 12. 7 12.5 15. 1 10.7 15.8 8.2 11.4 2. 8 Crouos of Ye.irs r->4i-i -i3 0.3 0.9 3.2 5.4 12.5 18. 9 27.0 33.7 34.5 30.6 30. 0 27.9 14.3 7.1 _? 1950-1=52 1.0 0.8 3.0 6.5 16.7 37.2 59.7 77. 8 102. 9 86.3 83.9 59.7 71.0 15.8 ".Mortality from Lung Cancer is Canada", 1931 to 19S2. These figures show strikingly the increase is rates be tween 1931 and 1952, and this increase is particularly marked after age 50, confirming an observation previously made, to the effect that lung cancer has probably been under-diagnosed in the older age groups in the general population. To use tbese figures for purposes of comparison, it is necessary to combine the rates for certain age groups is order to conform to the age distributions used in this study. Since the exact populations in sacb age group for tbc years indicated is not known. 0194 \ \ \ 63. this must be an approximation. However, tbe rates 3id be some what as ioUowj: Age Grouo 20.44 45.54 55.64 65 v Rate 5 27 69 90-95 These rates are, is general, lower than those developed /or the total (proved and suspected) cases ol lung cancer among tbe asbestos misers. The only large dillerenee, however, is in tbe age group a1 65 years and ever, and it is quite possible that tbe rate lor this group may have increased lor Canada between 1952 and 1954 as it did lor the Province ol Quebec. (Sec Table 21) A lurther comparison has been made with an over-ail rate obtained Irons the American Cancer Society lor respiratory can cer deaths is Canada in 1953. This rate, lor males, is 20.8 per 100,000, an increase ol 5 per 100,000 over Phillips' ln50-1952 rate, and compares with 25.5 per 100, 000 lor proved cases and 34.0 per 100,000 lor total cases among the asbestos miners in this study, it is tbere.'orc obvious that there are no important diifcrenccs between the rales lor asbestos miners and those 1or the general population ol Quebec and the Dominion ol Canada. 0195 Since ii proclitic thi: ajurti :or the wnitec state > ire more complete end, therefore, possibly more comparable to the c*ti for the mineri, age-specific rates were computed from 'Vital S'.iiutici of the United States", Volumes 1 and U. for 1952. These rales have been tabulated in Table 24. TABLE 24 Number of Deaths and Death Rates per 100,000 by Age Croups for the Adult Male Population of the United States--Data Prom - "Vital Statistics of the United States", Volumes 1 Cnd 11, 1912 Ace Croua 20.44 45.54 55.64 65 4 Total -Poouiatior. 24,544,000 8, 065,000 6,340,000 5. 670. COO 44,619,000 Case s 863 2979 6254 64 83 16,599 Rate oct IOC, CC0 3.6 36.9 98.6 114.3 37.2 It is apparent that these rates eompare favorably with those (or the asbestos miners as shown in Table 6. Still other rates for the United States were obtained from the American Cancer Society, and for males, these were 25. 3 per 100, 000 m 1953, and 26. 0 per ICO, 000 in 1955. They arc not identical with the rat* calculattd from the Iigurcs of ihv oiiice of Vital Statistics, but this is possibly because the American Cancer Society rates are for males of all ages. Nevertheless, they, too, compare favorably with the rates of 25 (or 34 for total catesL outajun; among the asbestos miners. 0126 \ V \ _c. 65. fieturmng :o a comparison between :hc asnesios m.r.e.-j u .d persons who are exposed to Asbestos in one form or Another (as distinguished Jr err. the general population groups just discussed, *55 have no exposure] an interesting observAtion esn be deveieped by se duction. Kucper ' ' has stAted that there Are About 35,003 persons exposed in the United States, and we have found that the Canadian mines employ about 8, 000. Elsewhere, it has been estimated that the workers in England who have exposure total betwteo 3, 0CC and 5, 033. With workers in Africa, Denmark, Norway, and other countries, at least 50, 000 persons must be exposed throughout the wer.d, and 1: can be assumed chat this number has been [Airly constant in the 20 years siacc 1535 when the first case of asbestosis with lung cancer was re ported. At least a million man-years of exposure has thus beer, accumu lated, and this figure can be divided by tbe approximately 150 cases of lung cancer with asbestosis reported during the 20-year period. Tats gives a rate of 15 per 100, 000 which is at least indicative that any lung cancer rate which can be calculated (or workers exposed to asbestos dust is not much greater than that for the unexposed persons. 0197 CiTtir'.jjr. Sutw.-cn Co;..*.::e ;\g cce-.r A soe >;oi - P r Artjj Jr.-; jc.octcc uour.t.cs To corr.pa.-c lung cancer mortality race* m the coun ties surrounding the asbestos-producing areas witr. another group of counties in which no asbestos miners arc likely to resice, the rates were computed on the basts of figures for the years 1950 through 1955. Toe eight counties selected for comparison were Argenttuil. Chateaugay, Montsagny, Portneuf, Richiaeu, Rivieredu-Loup, St. Kyaeintfte, anc Terrebonne, mainly because they re present a wide geographic distribution throughout the Province. The counties selected because of their proximity to the asbestos mines include Artnsoaska, Seauce, Drummond, Prontenac, Mtgaatie, Richmond, Scerbrookc, ana Wolfe. Table 25 shows the number of lung cancer deaths for the yesrs 1950 through 1955 for each of these counties, ana a mortality rate, based on the adult male population in 1952. To empr.asize the comparison Megantic County has been showr, separate;)-, as -*s tac Province of Quebec and also the Pro vince aim the eight soesios-proaucing" counties subtracted. Be cause ot its unique u.-.^ cancer death rate, Montreal et isle ee Jesus ha# also ocen -istec m orccr to provide further comparison.  r r~ \ N um ber o f Lung C ancer D eath* and Rale p e r 100.000 M a n -Y e a r* <6 m+ ** w * VK^ * ^ *0 * IOwn rfr 7 F 1^ R O* 9A O A ? 2 i? A G<99 68. It is apparent Xrore the table that the lung cancer ceatc rate lor the eight counties immediately surrounding the asbestos* producing areas is practically identical with that of eight counties elected lor comparison. While Megastic County has a rate Dearly twice that 0/ the combined eight selected counties, it is lower than the rate lor the Province, and considerably lower than the rate lor Montreal. The figure for Montreal would certainly be higher except for the very low numbers of deaths reported for 1980 and 1951, and it would appear that 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, and this would result in a rate of *0 per 100, 000. The only possible conclusion from this comparison is that there is no evidence that the persons who live in the counties surrounding and adjacent to the asbestos-producing areas have any greater incidence of lung cancer than those who live elsewhere in the Province. Discussion of All Recorded Lung Cancer Cases. Li vine and Dead, at - .-sips ana Thc::ord Mines Although a simple enumeration of all the known or sus pected cases of cancer of the lung in these areae Has no particular value from a statistical point of view, it is of interest to summarize 0200 e c_ such cases /or the record. There *err r.;nc deat.ls pr;sr :o '.he seginnjS) 0/ the time period covered by the srudy, inducing one in which the diagnosis was mediastinal lymphosarcoma. All 0/ these nine cases occurred at Thet/ord Mines. It is somewhat surprising that there is no record 0/ any lung cancer deaths among the Asbestos group is the interval preceding the beginning 0/ the study and equally o that so cases have bees reported in 1956 and 1957. During the period covered by this investigation, there were six proved cases and three suspected cases at Thet/ord Mines, as well as three proved cases at Asbestos. Through 1956 and to date m 1957, there were eight deaths at Thet/ord Mines, six 0/ which were merely suspected and included such diagsosea as mediastinal lymphosarcoma, mesothe lioma, cancer e/ the leg with metaatasea to lung, absess 0/ lung, and cancer 0/ the pancreas. One other was diagnosed on the basis 0/ x-ray only. In addition, there are sow living /our caats in which the diagsoatic evidence is strongly suggestive 0/ lung cancer. This is a total 0/ 33 cases 0/ all types, including ten "suspected" but unproved cases, and four that are still living. The remaining 19 constitute the total 0/ proved cases 0/ cancer 0/ the lung in both areas since 1940. Sixteen 0/ these have been at Thet/ord Miner and only three at Asbestos, all 0/ which occurred during the period ol the etudy. The proved caret averaged 59 years 0/ age at death, and varied between 37 years and years. Their working span covered 7C. periods varying between a minimum oi 14 years and maximum o! 17 years. Only three men bad lest than 25 years oX employment in the industry. Seven itnon; those on whom such inXorraation is available had a weighted exposure placing them is category HI, asd six worked is as exposure represented by category 1. Although they were subjected to post-mortem examination, there were three among these proved lung cancer cases is which we do sot have inXormation regarding the presence of asbcstosis. OX the remaining 17, asbcstosis was present is nine, although it was minimal is two. asd two pathologists disagreed regarding its presence m one. igbl eX the proved lung cancers, thereXore, were not accompanied by aabestosis. 71. ' VI. SUNL'.USV ANQ CONCLUSIONS Interest m the question of whether there may he in nsociation between lung cancer ud asbestosis er exposure to ashestot has been evident since the report in 1935 by Lynch *nd Smith of & cnee in which lung cancer and asbestosis were both present. At additional cases in which the two diseases coexisted were reported, a causal association appears to have been gradually accepted by many authors, although a few workers considered the correlation to be in conclusive, Cases of lung cancer which had occurred among the as bestos miners in Quebec bad been carefully recorded over the years, and the present study was commissioned in an effort to determine whether a causal relationship did, in fact, exist between exposure to asbestos and cancer of the lung. Hefercnee to the literature shows a remarkable uniformity both of method and of conclusions, la general, the method has been to study a circumscribed senes of cases of asbestosis and to enumerate those in which lung cancer occurred. The series may consist of cases coming to autopsy or of death certificates mentioning asbestosis, and tbc total number has served as the denominator by which the number of lung cancer cases is divided to produce s certain ''incidence rate". This rate, as reported by various authors has been consistently high, and its uniformity is indicated by the following tabulation. 0203 :z. r\ Author Merewether Wedler W ye r s Lynch L Cannon Gioyne Totals Asbestosis Deaths 344 92 US 40 121 712 Caacer of Lur.^ SS 15 17 3 17 107 Percentage Incidence 16. 0 16.3 14.8 7.5 14. 1 15.0 The notable characteristic el all previous publications i* the adherence to tbc development of a percentage relationship ia (63) a relatively trnall aad very selected group of cases. Only DoU, among ail of these authors, has described a representative population group aad studied it for tbc mortality rate from lung caacer aad com* pared this rate with that for a control group. His iavestigatioa dealt with only 113 aes ia the study population. Since most earlier studies bad been limited to caumeratiag tbc lung cancers found ia certain selected samples, such as cases coming to autopsy or death certificates ia which asbestosis was mentioned, it was apparent that they could not fulfill the requirements of an epidemiological and statistical approach to the problem. The pre sent stucy 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 tbs.asbestos mines m Quebec, based on medical records at tbc two maaa locations 0204 73. of these operations. Cohorts were defines according to certain cri teria sad all workers who met these criteria were included in the study. Through their medical records, data relative to their charac teristics were collected and their status at the end of a six-year period of observation was determined. In the case of those who bad died, an exhaustive search of death certificates and insurance records was carried out in order to determine as nearly as possible the exact cause of death. Mortality rates from lur.g 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 aad for the other population groups were made according to accepted statistical methods which have been explained in some detail in section IV. Record* were obtained on 6091 persons who fulfilled the criteria of our cohorts. It was not possible to trace 133 of these for the whole period, but 5771 of the remaining 5958 were found to be still living in 1955 or later. Of the 18* tmown dead, cancer of the lung was considered to have been reasonably proved in nine and to be strongly suggested m three. The members of the cohorts were studied with respect to sge, length of employment, a weighted average of their exposure, and their smoking habits. Four thousand, six hundred and seventy-three i // u. were four.: :o be smokers *itb;r. the definition of that term as usee in this study. Thirty-four percent of the cohort were more than 45 years of age, and 3CT. bad been employed for longer than 20 years. Thirty percent had a weighted exposure which placed them in cate gory ill. The mortality rates for lung cancer, as computed on the basis of six "proved" deaths among the Thctford Mines cohort and three "proved" deaths among the Asbestos cohort, were 27.6 per 100,000 for the Thctford Mines group, and 22.2 per 100,000 fqx'the Asbestos group. When the three "suspected" eases were added, the "total" rate for the Thctford Mines cohort rose to 41.3. The rate for the combined cohort was 25. 5 per 1 00, 000 for "proved" cases, and 34 per 100, 000 for "proved" and "suspected" cases. The importance of the suspected but unproved cases in determining these rates has been reiterated he- . cause it is likely that such cases would not be included in the statistics for the general population. According to the findings in this study, the mortality rate from lung cancer docs not appear to increase with length of exposure or with degree of exposure, a fact which presents strong evidence agamst the carcinogenicity of asbestos. Oe the ether hand, the study indicates that cigarette smoking is a very important factor m the in cidence of cancer of the lung. A comparison of relative frequency of lung cancer and asbestosis is less reassuring. but we believe that this is because of an 0*06 / *5. _'.c: - r*> :r-._-.; uits. .:.t i: indicate by the medical records is far below that watch *ou.d be expected on the basis of ail previously published figures. Naruraliy. when the eases of lung cancer are compared with an artificially low figure, its relative incidence will be higher than it should. However this may be, 12. 5% of the recorded cases of asbestosis m this study developed lung cancer, a figure slightly lower than those quoted by r authors who confined themselves to this type of comparison. Comparison of the experience among the asbestos miners with that of various segments of the unexposed, comparable population shows that the observeo number of deaths among the miners is not significantly greater. The rate for proved cases among the asbestos miners (25.5 per 100,000) compares well with the rate of 22.5 per ICO, 000 for the rest of the Province, and 20. 8 per 100,000 for acull males throughout the Dominion of Canada. It also compares satisfacto- rily with rates of 37.2, 25.3, and 28.0 obtained from various sources for adult males in the United States. Finally, in this matter of com* parison, it would appear that the world-wide experience of persons ex posed to asbestos dust is not worse with respect to lung cancer than that of the unexposed population. The counties surrounding the asbestos-producing areas, and in which it is presumed most of the asbestos miners live, nave almost t identical mortality rates with those of eight counties widely scattered 0207 i Tfe. through the Provu-.ee, end art lower than those 1or the remamaer c.' the Province, and much lower than the rate lor Montreal. Since 1940, there have been 19 cases in which the diagnosis 0/ primary cancer ol the lung may be considered to have been proved. Approximately hall ol these eases were associated with as* bestosis. All but one died in the recognised "cancer age" and at least r one-third had only the lightest exposure (category 1] to asbestos dust. Conclusions On the basis ol a carelul and detailed study ol what are believec to be complete ana reliable data, it seems lair to conclude that the asbestos miners at Thetlord Mines and Asbestos m the Pro vince ol Quebec do not have a signilicantly higher death rate Irom lung cancer than do comparable segments ol the general population. Despite this, the results suggest that a miner who develops the disease asbestosis does have a greater likelihood ol developing cancer ol the lung than a person without this disease. We suspect, however, that under reporting ol asbeslosis cases bad led to a laJlacious linding in this con nection. The death rate irom lung cancer in the areas continguous to the asbestos operations is comparable to that in areas widely scattered throughout the Province ol Quebec and is lower than in some urbanized * * V * * ** f.-.m t.-.u Province, The present study indicates that the effect of cigarette EOius; it a much more important coci.ccition in the production of lung-cancer this is exposure to asbestos, and m thus respect, it tends to confirm recent studies dealing with the effect of smoking. The value of this investigation wouid be considerably en hanced by continuing the observation of the cohorts formulated herein on a year-by-year basis. It is strongly recommended that the chest x-rays of all workers be submitted to an independent reading for the diagnosis of asbestosis, since an inaccurately low incidence rate for this disease creates an artifically high relative incidence for lung cancer. 0209 78. v::. bisliocrapky 1. Adler, I. . 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