Document 37LzDgEXOwB3kMkaGVvO67Drx

i' Restricted Copy_23. t ,n *J * . * '* * '. *. . .. ^3 C0XFlDErrTL4L\. INDUSTRIAL HYGIENE FOUNDATION OF AMERICA, Inc. y?.T. v -Vv:..-. r/.: -:Vv . ;:.V N- >400 FIFTH AVENUE ... PITTSBURGH 13. PA . ' fv'*; r tQO^ AN EPIDEMIOLOGICAL STUDY OF . LUNG CANCER ,. IN ASBESTOS MINERS : /- . . Report to it * H v- QUEBEC ASBESTOS MINING ASSOCIATION Quebec, Canada . v;- :-V. . .... . . .. ..!. ' . . j Sepptteember. 1957 * . .. *:.* * . . , . ..... .... * r v* = * r-d . V-i&V- - ;V:i 7 -*}. ... .,T.^ SC-ALL-07200 SCF-ALLF-01885 J Industrial Hygiene Foundation of America, Inc. 4400 Fifth Avenue Pittsburgh 13, Pa. AN EPIDEMIOLOGICAL STUDY OF LUNG CANCER IN ASBE5TOS MINERS For QUEBEC ASBESTOS MINING ASSOCIATION Quebec, Canada July, 1956 to July, 1957 l ' By f Daniel C. Braun, M.D. Medical Director .-V i. September, 1957 By: C. Richard Walmer, M.D. Managing Director TABLE OF CONTENTS Page Foreword............................................................................................................ i Glossary............................................................................................................ iv 1. Introduction............................................... E. Critical Review of Literature.............................................................. I 5 HZ. Principles of the EpidemiologicalMethod 13 IV. Collection and Analysis of Data......................................................... 18 V., Results and Interpretation................................................................... 26 Asbestosis and Lung Cancer. . ............................................... 47 Comparison of the Cohort Experience with that of the Province of Quebec, Dominion of Canada, and theUnited States...............................35 Comparison Between Eight Counties Adjacent to the Asbestos-Producing Areas and Eight Selected Counties.......................................... 66 Discussion of AU Recorded Lung Cancer Cases, Living and Dead, at Asbestos and 'Thetford Mines. ........................................ 68 VI. Summary and Conclusions............................................ ~1 VU. Bibliography................................................................................................ ~S i. FOREWORD The success of a study of the type herein reported de pends ve.ry 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 Or. Paul 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 maintained assisted considerably in the preparation of the material relative to the worker population. Data on population figures and on the causes of death in the Province of Quebec were obtained with the utmost assistance and co operation from Dr. 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 in many ways, including the location and interpretation of death certificates. Especially helpful in this part of the work was Miss Gauthier of Dr. Parrot's staff. The same helpful I 11. cooperation was rendered by Mosers. Hardy and Hopkins of tbo Sun Life. Assurance Company of Canada in Montreal, who made available their records of the death claims paid under the group policy cover ing the workers at Asbestos. Valuable suggestions for the conduct of the study were made by Or. J. A. Vidal, Chairman of the Silicosis Board, and Or. Guy, Pathologist for the Board, as well as Or. Gregoire, Deputy Min ister of Health for the Province of Quebec, and Drs. Sisaard. Oufresne. and Groulx, in Montreal. Statistics for the mortality rates for the Dominion of Canada were obtained through the kindnesa of Dr. Dean f*. Davies, Administra tor for Research on Lting Cancer for the .American. Cancer Society, and those for the United States were graciously furnished by Miss Guralaick 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 Or. Kenneth W. Smith, Medical Director of JohnsManville Corporation, and Mr. Ivan Sabourin, General Counsel for the Association, in making the necessary contacts, in travel arrangements, and in so many other ways, is gratefully acknowledged. The methodology of this research is believed to be unique 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 Ui. to assure a proper epidemiological approach, and all biostatistical applications of the findings were provided by Mr. T. David Truan. formerly of the Graduate School of Public Health, University of Pitts burgh, and the staff 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. IV GLOSSARY For the purpose of clarity and uniformity, the terras used is this report are herewith defined according to the manner of their use. . Asbestos workers: Workers exposed to asbestos dust in other than raining operations. Asbestos miners: Workers engaged in the raining and prepara tion of asbestos in the areas under srudy. Asbestosis: A generalized fibrosis of the lungs diagnosable by x-ray, or by microscopic examina tion of the lung tissue, but not necessarily accompanied by symptoms or by disability. Cohort: A segment of the population, defined accord ing to certain criteria, and representative of the whole population. Specifically in this study, a group of asbestos miners having at least five years of exposure in the industry add who were in 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 undiiferentiated, round, or "oat cell" histological types. Primary cancer of the lung means sucb a neoplasm originating la tbo lung, ana not secondarily in the lung as the result of a metastasis from another primary location in the -tody. Smoker: As used la this presentation, the term smoker refers to a cigarette smoker, h-bitually sraoklag more iban five cigarettes per day. Persons who smoke pipes or cigars exclusively were not-considered to be smokers for the purpose of this study. I. INTRODUCTION Ever since the pronounced increase in tbe incidence of lung cancer among males became apparent, there have been attempts to associate it with one or another of the various elements in the en vironment of roan. The approach used by some workers has been to suspect one or several substances and then set about in an intensive Bearch for lung cancer among persons who have had any exposure to those compounds, la this connection. Smith writes; "The ten dency of authors reporting the coincidental occurrence of primary lung cancer with silicosis or with any other, theoretical etiologic con ditions, has been to emphasize the percentage relationship in extremely small series of cases, with control cases which are not in any way comparable." It would seem inevitable that asbestos should come under scrutiny in this manner, because prolonged exposure to this material is known to'cause a specific type of pneumoconiosis, and because persons who show this form of pneumoconiosis often come to autopsy and pro vide a ready source of material for study. It was in this way that re ports of this simultaneous occurrence of lung cancer and asbestosis be gan to accumulate after tbe report of a case by Lynch and Smith Ln 193S. Within tbe next ten years, about 15 additional cases were reported, and in 1946 Merewetber reviewed all deaths from asbestosis re corded in England since March, 1924. Lung cancer occurred, according to Merevetbar, is 13.2% of these eases. Continuing this study to include December, 1954, Merewether counted 55 cases of cancer of tbe lung among 344 cases of asbestosis, raising the incidence to 1.6%. (92) Gloyne, whose work is also frequently referred to as establishing 'l a connection between asbestosis and cancer of tbe lung, reported in 1951 the results of bis findings on 1205 autopsied cases. This series included 132 asbestos workers, of whom 121 showed asbestosis. Cancer of tbe lung was present in 14.1% of these asbestosis cases. In 1941. Nordm&nn and Sorge claimed to have produced lung cancer in mice which they exposed to asbestos dust. * Since 1951, additional cases of cancer of tbo lung coexisting with asbestosis have been reported, and, according to Hueper about 100 such cases had 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 (205) ' tbe lung. Werber in 1952, stated categorically that in 7% to 17% of cases of asbestosis, after a latent period of about l l/Z to 20 years, carcinoma becomes established in the lung. On the other hand, sot all authors accepted the alleged associa, (177) tion without reservation. Saupe in 1939 had reported that be had discovered no cases of lung cancer among 620 cases of asbestosis which (104) be bad examined; and in 1942, Holleb and AngrisC expressed the opinion that the number of cases of asbestosis with lung cancer was too ). small/or statistical evaluation. In 1947, Wegelius reported 126 radiologically diagnosed cases oZ asbestosis among 476 workers in Finland, and found no cases of lung cancer in this group, Goldblatt and Goldblatt in their sectiIon of Merewetber's latest book, ' ' state: "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 as 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. . Meanwhile, the Canadian Johns-Manville Company in Asbestos has been alert to the whole problem, and at the Tbetlord Industrial Clinic, Dr. Paul Cartier was studying the situation s' among a working population of about 6000, and made notable contri- * (42-44) butions to the literature just cited' . Between these two areas, a number of cases bad been recognized and tabulated by the spring of 1956. At this time, at the suggestion of Dr. Kenneth W. Smith, Medical Director of the Johns-Manviile 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 order to discover whether the incidence of lung cancer was, in .fact, greater amoog asbestos miners than among the general popula tion, and whether there was a correlation between lung cancer ind the disease asbestosis. The Foundation submitted, in March, 1956, a pro posal for such a study based upon a preliminary survey 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 Sabourin. Esq. 5. n. CRITICAL REVIEW OF LITERATURE A careful review of the published material on this sub ject shows that 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 ie 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 of 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 gave any data on exposure and dust concentrations, and even Doll's paper merely mentions "scheduled" areas, by which i9 meant, "those areas where processes are carried on which-werc scheduled under the Asbestos Industry Regulations of 1931 as being dusty." There is, furthermore, a complete lack of definition of terms as used in the published literature. For example, the term 6. "bita(i", ao uood, may refer to ebangot observable only by microscopic examination of the lung tissue, or it may mean a radio logically detectable condition. Most of the published reports obviously included women among their cases, but some of them do not give the number or pro portion of women involved in 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 (122) Hueper in 195$, 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 had originated In England, and since no asbestos mining opera tions are carried on in that country, that most of.the reported cases have involved workers in the textile or fabricating industries. Such factors as smoking habits, family history of cancer, length of time in the industry, and age of the individual case are also notably absent in the majority of these reports. With this understanding of the limitations of the existing literature with respect to epidemiological generalization, it may be of value to consider in somewhat more detail some representative earlier publications, a few of which were referred to brieily in the previous section. 7. One of the most detailed studies and one which deserves (63) the most serious consideration is that reported by Ooll in 1955. This study reviews causes of death among asbestos workers based on coroners' records. It also attempts to estimate the risk by studyi' ing records of men who worked for at least 20 years in exposed situa tions. Ooll 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 tbe 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 (61 cases of lung cancer) suggests--but does not prove -- that lung cancer is an occupational hazard of asbestos workers." Neither this article or any previous one which we have examined presents aay figures to prove that asbestosis is an infrequent occurrence. Es timates of tbe number of persons potentially exposed to asbestos dust in tbe United States alone vary from 10,000 to 3S,000 and the incidence of asbestosis of any degree might be higher than Doll imagines. This study, like so many others, involves autopsy records. Tbe number of persons involved in tbe statistical analysis is only 113 representing only 1,042.25 man years of life. It is also true that in selecting men who had been employed for at least 20 years, the study automatically excluded those who died from other causes after shorter employment. 3. It also seems (hat this review does not add any new cases to the literature, although Hueper in 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 a statement which it contains to the effect that "the strongest evidence that it (lung cancer) may be a hazard (in. asbestos workers) has been produced by Merewether and by Gloy-ne. " 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 ol 1205 autopsies on persons who bad worked in v.irious dusty occupations. This num ber included 132 asbestos workers, of whom 121 showed "pneumoconiosis" --presumably asbestosis. Prim.iry cancer of the lung occurred 17 times in this group, an incidence rate of 14.1% for lung cancer among autoosied asbestosis cases. There were in his series 796 cases with silicosis, and 6.9% ox these also showed primary cancer pi the lung. The incidence of lung cancer in. other forme of pneumoconiosis was 6.7%, and in 169 cases which proved not to have any type o: pneumoconiosis it was 3.3%. Gloyne considered "the mortality of the asbestos workers" to be "disturbing". First of ail, it is obvious that the paper does not deal with the "mortality 61 asbestos workers", and secondly, it must be borne in mind that all of Dr. Gloyne's cases were submitted to bim 0 for iiudy because (be findings were unusual for uncomplicated pneumo coniosis. Presumably, all cases, including those of asbestosis, in which the findings were not considered unusual were never brought to Or. Gioyne's attention. As a matter of fact, in the same paragraph 1 in which he expresses concern over the incidence rate in asbestosis. Or. Gloyne himself points out that the rate for lung cancer based on necropsies at the London Chest Hospital was 21.3% while the figures of the Registrar-General showed only 2.l7>. He thus recognised that autopsies on a certain selected group of cases were not representative of the general population. It would seem, then, that notwithstanding the value oi Dr. Gioyne's work, its importance as an index of the pre valence of lung cancer in asbestotics has been misinterpreted by those who have quoted him. All that it really shows is the fact that in a group of 121 cases, selected for special study primarily because they seemed abnormal by preliminary examination. 17, or. 14.1% had lung cancer. ' Nlereweiher In 1947, in the report of the Chief In spector of Factories, reviewed all cases reported between 1924 and 1946 in which as'oestosis was the cause of death or a coexisting con dition. This work was later extended to include all such cases reported up to December, 1954, by which time there were 144 deaths including 209 males and 129 females. Among them were 55 cases (16%) of cancer - of the lung, 41 in males and 14 in females. It is quite possible that a large number of asbestotics who did not die of their asbestosis, or in i i 10. whose death certificate it was not mentioned, may have been missed. The import of tbis 167* is enhanced by the simultaneous statement that the incidence of lung cancer in autopsies of the general popu lation is only 1%. The danger of attempting to compare a rate found I. in 344 caeee with the rate for the general population without respect to age, occupation, and many other variables, such as smoking habits, is obvious, Lynch/142* who with Smith had reported the first case in 1935, reported four cases of carcinoma of the lung in a series of 49 autopsies on workers in 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 asbea- tosis. Lynch, himself, points out that, although this is .an incidence of 8.2?, "both figures are too sifoail for very serious statistical types of calculation." Nevertheless, later writers have used this paper to strengthen the case for an association of carcinoma of the lung with asbestosis. it is of interest to note that Klor: found only four in stances of lung cancer in 478 cases of asbestosis, a series 11 tiroes as large. . . Behrens, as quoted In Nierewether estimated that, of 309 cases of asbestosis in the literature, 44 showed associated cancer of the lung--giving u incidence of 14,25^, This is another case of generalizing an incidence obtained in a group of cases which were il. undoubtedly reported only because aome of them showed lung cancer, to possibly hundreds of asbestotics whose cases were never reported. The same applies to the conclusion of Teleky 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. ' Werbcr who made the unequivocal statement that lung cancer would result in from IS to I 7% of cases of asbestosis. allowed himself considerable 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 "Nontuber. (7b) culous Diseases of the Chest" where the authors say simply, "an cx. ccssive incidence of pulmonary cancer has occurred among workers in other occupations, such as asbestos industries, nickel-cppper refineries, stokers in generator plants, etc." without substantiating reference. As an illustration of the ease with which a few reports which merely suggest a certain conclusion can, through the lack of a sufficiently critical attitude, be summarised to produce the conclusion in a definite ` <f>9) , form, m editorial In the Journal of the American Medical Association mentions the work of Wedler and the report of Merewether and then es. tablishes the causal relation betWcen asbestosis and cancer of the lung as settled. As a final convincing argument, it refers to "recent experimental u. observations (by) Nordmann and Sorge . This is the experiment in which squamous carcinoma was said to have been produced in about a dozen white mice, and which has not been duplicated by any other in vestigator! 1 Perhaps no one has written so extensively or so dogmati- (109-124) cally on the subject as has Hueper . la. 1955 he reviewed the cases reported prior to that date and enumerated a total of 99. Eleven of these were those discussed by Doll (63) and appear to have been cases covered by other authors. Eight were discovered by Kenna- way and Kennawav in la analysis of death certificates and, unless ' (vterewethor study was incomplete, these eaeee should have been in cluded in his report. Of the remaining 80,. it is quite possible that the 31 contributed by Merewctber and the 17 by Gloyne contain some dupli cation with each other or with othe.r English authors. In the same paper, Hueper 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 asbestosis! 1 13. UI, PRINCIPLES OF THE EPIDEMIOLOGICAL METHOD As has been Indicated, much ol what is now thought to be pertinent concerning the comparative frequency of lung cancer in different population groups hqs been developed from the analysis of clinical material, particularly surgical and autopsy records. This has been supplemented to some extent by the reported impressions of various clinicians based upon their personal observations. 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 methods. 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 in individuals, epidemiological research involves the investigation of the disease as a masspbeaoroenon. It seeks to discover what propor tion of persons in & 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 tse approxi mate number of cases of this disease which will develop in a population of specified sice, composition, and subject to a given environment. It proceeds by first carefully and accurately describing character istics of the disease in different population groups and its essential objective is the formulation, testing, and verification of generali zations concerning the disease in question. In order to apply ehis method of investigation to tbe pro blem under discussion, the Foundation was of the opinion that a study should be planned so as to provide; 1. A well defined population group. 2. Available data for all members of this pop ulation, inducing the healthy as well as tbe ill. 3. A sample which is truly representative of the population. 4. Reliable and valid observations relating to the problem of the study. ' A serious defect, common to most of tbe 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 peop.le. - In order to draw a generalization regarding all asbestos workers.it is necessary for a study to include living persons as well as the dead. Limiting tbe investigation to autoosied cases, as has en frequently done in earlier studies, still further restricts its use I i E: !* 15 in generalization. The problem with which (he Quebec Asbestos Mining Association is concerned is whether asbestos miners ex perience more lung cancer than does the general population. The answer necessitates tbe 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 its increasing numbers, is still a disease of low incidence; that is, in a given population not many persons will contract this particular disease. This fact requires that large samples or group must be studied to provide meaningful results, Recognizing tbe difficulty of obtaining such large samples, most earlier writers deviated from the epidemiological method and sought to circumvent the requirement of observing well persons by: . I-. Comparing tbe relative freeuencv of cancer in various sites. * Z. Comparing the relative frequency of cancer in a group of hospitalized 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 of cancer may be increased merely by reason of a decrease in the incidence of cancer of other sites. This coaid be true even though the incidence of lung cancer remained constant, or if it de creased less rapidly than that of the other types. Attempting to compare two population groups, looking only . .1 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 in 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 measure 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 cases of any kind'than would be found in 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, but the use of this information in drawing generaliza tions is necessarily restricted. It lo the obligation oi both the investi gator and of those who read his report to make proper comparisons and to draw only those conclusions which are valid and justified. A good statistical study of cases of cancer of tbe lung occurring in a group of autopsies can lead to a proper inference concerning tbe frequency of lung cancer among cases coming to autopsy, but only to such cases. For 17. i information from such a study to be projected to some larger rtroup, it is necessary that the autopsies represent a good sample ot that larger group. To assume that such is the case in any particular series is dangerous and likely to be false. I 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 generalization, nor can the generalization 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 particular i.nvestiga- * tion. ' The present study, in contrast to the earlier works, has been planned to utilize the epidemiologieal method, A well-defined group of asbestos miners has been established in such a way that it constitutes a good sample of the whole population of asbestos miners in Quebec. Data for ail members of this group have been collected and analysed. Those concerning lung cancer have received most careful consideration. De tails of the methods employed will be set forth in a later section, but the type of approach is considered to permit of fair comparisons and valid generalizations. ' j } i ] !k i i< 18. IV. COLLECTION AND ANALYSIS OF DATA A preliminary survey of potential sources of Information in February of 1956 involved discussions with the physicians in charge of the asbestos companies' programs and with clinicians, pathologists, representatives of City and Provincial health departments and of the Canadian Cancer Society, and other interested persons. It was found that morbidity data, although somewhat limited, were available from such sources as the hospitals in Montreal and Quebec City, and the 13 Cancer Detection Centers in the Province. However, because of the high mortality in lung cancer, it seemed .advisable to depend upon data relating to deaths. 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 formation 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 directed to the collection of data relating to all workers who had been . processed through the clinic at Thetford Mines since its Inception in 1947. Similar information was obtained regarding all workers at the Canadian Johns-Manville Company in Asbestos. Data from the clinical records included the age, family and personal medical histories, smoking habits, number of years of exposure, an estimate of weighted exposure, t . 19 and the course of the individual's health status or the cause of his death Although the data in these two instances were not exactly similar in form, the inclusion of records from the personnel department at As bestos 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 Thetford Mines "cohorts" which could be well defined, should be representative of each group, and could be followed (or a de finite 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. AH 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 in the original cohorts who remained unaccounted for when the living and the known dead bad been tabulated. They represent men who had left 10. employment through retirement or resignation, eventually, ail but a small number of these were accounted (or as either living or dead, and in the latter event, the cause of death was substantiated in a similar manner, and the results added to the original list of deaths. I Death certificates for the Province of Quebec for the years 1952 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 in 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 or not an autopsy was performed. Cases in which, lung cancer was given as a cause of death, hut in which it was not specified as to whether the cancer originated in the lung, were also reviewed in an effort to in clude all instances of primary carcinoma of the lung in 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, "rom them, death rates for the general population of Quebec and of individual coun ties were calculated for specific years and analyzed by cause. Practically all employees of the Canadian Johns-Manville Company are covered by a group policy of life insurance which, fortunately. l 21. nearly all of them continue to carry when they retire. A very few are not covered by this policy, and those who leave the industry for one reason or another except retirement usually are no longer covered, but this is likewise a small number. As an additional check upon the 1 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 In 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 Manville 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 from the same cause among specific segments of unexposed persons. All lung'cancer deaths, both suspected and proved, were carefully analyzed to determine possible relationship or correlations between the development of lung cancer and any factor known from the 11. clinical records such as family history of cancer, personal history of heavy smoking, coexistence of asbestosis or exposure to asbestos. In addition to this analysis of deaths occurring in the co horts and during the years under observation, every known death from cancer o( the lung, a< well as every case diagnosed but still living, has been tabulated and analyzed. They will be discussed separately from those included in the population and time-interval under study. A comparison o: lung cancer mortality- in the asbestos pro ducing counties has been made with that in counties which are far re moved from the asbestos mines and in which, presumably, no asbestos * miner s live. ' Finally, in order to broaden the comparison of death rates in different population groups, the rates have been collected for Canada generally, and for the United States, according to the most recent pub lished and unpublished material. In order that the method by which these comparisons have beer, made may be more easily understood, it seems advisable to discuss briefly some of the fundamental statistical concepts which have been ' followed. The' principle of calculating the probability of a given sample representing the true condition of a large group can be Illustrated by imagining a container in which there are 1000 marbles of which 900 are white and 100 black. The actual probability of drawing a black marble :s one in ten.or . i. However, should a sample of ten marbles be drawn 23. from the container, it would not be unlikely (bat two, three, or even no black marbles would be among them, even though the "expected" number would be one. On the other hand, if all ten were to be black, that sample would unquestionably be "extraordinary". The following 1 tabulation shows a calculation of the probability that a given number of black marbles will be found in a sample of ten: No, of Black Marbles in Samole 0 1 2 3 4 3 6 7 8 9 j_0 Total Probability .3486784401 . 387.4204890 . 1937102 445 .0573956280 .0111602610 .0014880348 .0001377810 .0000087480 .0000003645 .0000000090 .OOOOOOOCOl 1.0000000000 From these probabilities, it is evidsnt that one might ex pect a sample of ten to include no black marbles or one, two, or three, but for the sample to consist entirely of black marbles would be ex pected only once In 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 24. marbles in slightly more than one trial out of 100. The actual prob ability of this happening is .012795184, which is determined by adding the probabilities for 4 through 10. La practical applications of sam pling, the percentage of "black marbles" is, of course, unknown and *1 must be computed from the results found in the sample. There are limitations 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. U the range is wide enough, the probability may 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 size 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 If and the binomial distribution are quite small. It is based on the equation: e -no ,(no), x x1 Where e = 2. 71828 (the base of natural logarithms) n = number of man years subject to risk p s incidence rate x = number of cases observed The logic of the statistical approach may also justify a few words of clarification. Generally, Ln problems of this kind, one eets up a hypothesis, which in our case would be, "Asbestos miners do not 25. have a higher rate of mortality from luag cancer than the general popu lation." The hypothesis is then tested by means 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 llhely 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 some 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 band, the value observed, even though larger than, the expected value. Is no greater than might occur by chance in fewer than 57 of trials, we have insufficient evidence to reject the original hypothesis. Calculations and codclusions 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. 26 V. RESULTS AND INTERPRETATION The two cohorts which were constructed according to the criteria described in the preceding section have been considered in dividually and compared with each other 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 the combined cohorts Is shown below: Asbestos Cohort Original Cohort 2327 Lost Persoos Deducted 54 Final Cohort 2273 Living in 1955 (working and retired) 2224 Dead by 1955 Ca. of lung Questionable Ca. of lung Other Causes Unknown Causes . 49 3 0 46 0 Smokers Nonsmokers Unknown 1931 - 340 2 Thetford Mines Cohort 3764 79 3685 3547 Summary of Combined Cohorts 6091 133 5958 5771 138 6 3 123 6 2742 925 18 187 9 3 169 6 4673 1265 20 27. Tables 1, 2, 3, and 4 present age, number of years of employment, weighted average exposure and smoking habits of these two groups. It will be observed from Table 1 that the Thetford Mines workers had a higher average age than the Asbestos group (42 years vs. 39 years). Consistent with this'finding, Table 2 indicates that they also bad worked longer as asbestos miners (19 years as against IS years). . A comparison of the exposure to asbestos dust is presented in Table 3. AU workers were placed in one of 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 fOT each job category was determined after consultation with per sons familiar with the environment and conditions tn the various work 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 11, while the Asbestos group occupy mainly the extremes of exposure. For the purposes of calculation, the assumption has been made that the relationship between these categories is linear, and that category 11 is twice as dusty, and category 111 three times as dusty as category I. The fourth variable, smoking habits, was similarly tabulated and is shown in Table 4, A larger percentage of smokers is indicated here for the Asbestos cohort - 85.0% compared with 74.4%. 8 TABLE l Number and Percentage Distribution ol Asbestos and Tbetlord Mines Cohorts by Age ' Asbestos _S_ No. 20-44 45-54 55-64 65 Unknown Totals ay. /\ge 1602 447 185 39 - . 2273 19 * Less than . 5 % %_ 70 20 8 2 100% Theu'ord 1 Mines No. J* 2299 677 430 276 3 3685 42 62 18 12 8 100% Combined No. _% 3901 1124 615 315 3 5958 41 66 19 10 5 100% TABLE 2 Number and Percentage Distribution at Asbestos and Thetford Mines Cohorts by Length oi Employment Length oi Employ ment Asbestos No, _% 5-9 880. 10-19 864 20-29 342 30-39 168 40-49 17 50 4 2 Totals 2273 Av. Yrs.. oi 15 Employment 39 38 15 7 1 9 100% * Leas than . S% Thetlord __ Mines___ No. _% 915 1S34 S80 435 168 53 3685 19 25 42 16 12 4 l 100% Combined No. 1795 2398 922 603 185 55 5958 18 30 40 16 10 3 1 100% I I 29. TABLE 3 Number and Percentage Distribution of Asbestos and Thetiord Mines Cohorts by Exposure Category Exposure Category Asbestos No. % l a HI Unknown Totals Av. Exposure 969 564 735 5 2273 1. 9 43 25 32 * 100 7. * Less than . 5 % Tnettora 1 ines No. % 1062 1586 1037 0 ibis 2.0 29 43 28 0 100% Combined No. % 2031 2150 1772 5 5958 2. 0 34 3b 30 9 100% TABLE 4 Number and Percentage Distribution of Asbestos and Taec/ord Mines Cohorts by Smoking Habits Smoking Habits Asbestos No. % Smokers Nonsmokers ' Unknown Totals 1931 340 2 2273 85 15 100% Less than 5% Thetioro Mines No. % 2742 925 18 3665 74 25 l 100% Combined No. rt* 4673 1265 20 5958 79 21 Too?. ii J I( II 1 II ii L 30. This is a difference which could hardly occur by chance because of the Urge size of the sample. Therefore, it is likely that the differ ence is a real one unless the method of recording this information at the time of employment varies at the two locations. in spite of the minor -differences brought out by these comparisons, it wouid seem that the two cohorts are quite similar with regard to the variables of age, length of employment, degree of exposure and, 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 ? presents the year-by-year experience of the two cohorts and 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 been supported by an autopsy or surgical resection of the lung with microscopic examination of the removed tissue. In one case so con sidered, however, diagnosis was confirmed by bronchoscopy with visuali zation and biopsy. In another, although there was no autopsy, the diag nosis of primary cancer of the lung seems to bove been beyond question. The term "suspected" primary cancer of the lung was ap plied to those cases In which the diagnosis remains in doubt but some of the evidence points to cancer of the lung. There were three such cases. 31. TABLE 5 - Part 1 Study of the Asbestos Cohort No. Alive At Beginning Year of Year 1950 2273 1951 2267 1952 2261 1953 2252 1954 2243 1955 2231 Totals Cause of Proved Suspected Primary Primary Ca.of Lung Ca. of Lung 1 00 10 00 00 00 2 '0 3o Death Other Causes 6 5 9 9 12 5 46 Unknown 0 0 0 0 0 0 0 ManYears of Risk 2270 2264 2256.5 2247.5 2237 2227.5 13S02.5 "Proved" cancer of lung death .rate per 100,, 000 man-years of risk s 22.2 f------------ ) 13502.3 TABLE 5 - Part U Study of the Thetford Mines Cohort No. Alive At Beginning Year of Year Cause of Death Proved Suspected Primary Primary Other Ca. of Lung Ca. of Lung Causes Unknown ManYears of Risk 1950 3685 1951 3675 1952 3661 1953 3633 1954 3605 1955. 3579. Totals l 1 0 2 1 1 6 2 61 3680 0 12 1 3663 0 28 0 3647 1 25 0 3619 0 21 4 3592 0 31 0 3563 3 123 ."o" 21769 "Proved" cancer of lung death rate per 100, 000 man-years of risk = "Suspected" plus proved cancer of lung death rate per 100,000 man- 32 TABLE 5 Part III Study o( Combined Cohorts Combined death rates per 100,000 man-years of risk for Asbestos and THctford Mines "Proved" cancer of lung death rate1 per 100,000 man-years of risk 25.S { 9 , 35271.5 "Suspected" plus proved cancer of lung death rate per 100,000 man years of risk a 34,0 ( 12 . 35271.5 In two, no autopsy was performed but the clinical signs and symptoms were such that the death certificates read "cancer of the Lung", and "suspected lung cancer". The third case came to au topsy but there was a-dliference of opinion between two pathologists as to whether lung cancer was present. The term "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 the year was counted as a full man-year of risk, but one who died during the year was counted as one-half a man-year. Deaths occurring in these two cohorts, and In which lung cancer is considered to have been proved as a cause, are shown In tabulated form on the next page. Also shown are three deaths in the Thetford Mines cohort which have been considered as "suspected" lung cancer cases 33. ASBESTOS COHORT "Proved" Cases oi Primary Cancer of the Lung Name Age Smoker Exposure Died l. A. J. i. N. P. 3. R.M. 66 65 65 Yea Yes Yes Zb Yrs. in Cat, U 10-12-5) 34 Yr s, )in Cat. 1 5- 3-55 37 Yrs. In Cat. I 7-Z0-55 Au- Ashestopsv tosis Yes Yea No Yes No No THETFORD MINES COHORT "Proved" Cases oi Primary Cancer oi the Lung Name Smoker Exboaure Died Au- Ashes copay tosis 1. C. B. 2. A. S. 3. W. F. 4. L. D. 5. E. L. 6. A. R. 5? 48 6i 56 37 68 Yea 32 Yrs. in Cat* I 8-20-50 Yes No Yes 22 Yrs, in Cat* JJ 51 Yes Yes Yea 33 Yrs. in Cat III 4-30-53 Yes Yes Yes 30 Yrs. in Cat. U 11-22-53 Yes Yes Yes lb Yrs, in Cat. I 8- 5-54 Yes No mYes 28 Yrs. in Cat. 5- -55 Bronch . No "Suspected" Primary Cancer of the Lung Name Aje Smoker Exsosure Died Au Ashes topsy tosis 1. J. T. 2. R. V. 3. P. P. 49 46 65 Yes Yes Yes 32 Yrs. in Cat. 33 Y'rs. In Cat. 42 Yrs. In Cat. Ill 10-25-50 m 7- -53 u 9-30-55 No Ye 9 No No Yes No n. Ac Asbestos there were no cases in which the diagnosis was questionable, with the result that the race Cor "proved" cases In this cohort is the only one developed. At Thetford Mines, however, the three cases mentioned earlier were'placed In the category ot "suspected" primary cancer of thg lung. An indication of the impor. tance of these cases in interpreting the results of the calculations is desirable before further discussion of the mortality rates which are derived in later tables. For example, it happens that the rate found (or the Asbestos cohort is very close to the "expected" rate based on the general population figures for the Province as will be shown later, and on this basis, we should find five deaths from lung cancer among the Thecford Mines group. As was explained In the section on "Col lection and Analysis of Data", it would then not be unlikely (or six cases, to occur in our sample. This is-, in (act, the number ot "proved" cases found in the Thetford 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 view. Since the 95% level of probability in 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 hand; having found nine cases we are not above the 95% level and are not justified in rejecting the hypothesis. Nevertheless, the occurrence of nine cases in this sample would show 15. an increase in rate which approaches the significant level. Because of the tremendous Importance of the questionable cases in thi9 res pect, some detail regarding them will be given here. In one of these cases, the suspicion of cancer of the lung is based upon the x-ray interpretation and, although no autopsy was performed, the death certificate indicates that death was due to lung cancer. It is well known that the x-ray appearance of fibrosis, es pecially if a localized density or a superimposed tuberculous lesion i9 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 no' post-mortem examination, (n the third case, although'it was subjected 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 and pulmonary 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 disregarded completely. It is for this reason that mortality rates for the The (ford Mines cohort and the combined co 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 Ln the 16. Asbestos cohort fall into one age group, 90 that the rate tor that age category is exceptionally high. At Thetford Mines, a more even distri bution of the deaths by age developed a series of rates which are less extraordinary and, as will be seen, are not widely divergent from the expected rates for each age category. The unusual rate in the Asbestos cohort for the age group 65 years and over, is the sort of thing which happens when the sample is small. For example, of these three deaths, two were exactly 65 years of age and would have been in another age group had the limits been increased by one year. TABLJS 6 Number of Persons and Number of Lur.g Cancer Oeaths by Age Groups - Age Crouos Asbestos Lung C anc e r Persons Deaths Thetford Mir.es Combined Lung Cancer Lung Cancer Deaths Death s Persons Proved Total Persons Proved Total 20-44 45-34 35-64 65* Unknown Total 1602 447 133 39 0 2273 0 0 0 3 0 3 2299 677 430 276 3 3663 1 .1 3 1 0 6 l 3901 3 1124 3 615 2 . 315 03 9 3933 l l 3 4 0 9 1 3 3 5 0 12 Annual Lung Cancer Death Rates per 100.000 Man-Years of Exposure by Ago Croups Age Grouo Asbestos Total 20-44 45-54 55-64 65 Unknown Over-ail No one exposed 0 0 0 1232 71 Thetford Mines Proved Total 7 25 74 116 116 60 121 00 27. 41 Combined Proved Total 44 15 . 44 81 81 212 265 00 25 34 37. The rates by length of employment (Table 7) show that the two groups were quite similar in this respect. During the first 40 years of employment, the rate rises, on observation which seems plausible since the men were growing older. However, after 40 years of exposure there are no "proved" ^cases reported for a total of 240 men during the six years, or about 1440 man-years of exposure. When the "suspected" cases are added, one case does show up Ln this period. This would produce a rate of 69 per 100,000, again demonstrating the importance of these questionable but unproved cases to the final con clusion. because, if there were no cases in this number of men with long exposure, and if asbestos is a carcinogenic agent, it must bn con cluded chat these 240 men have demonstrated considerable resistance. This is a biological phenomenon which has boon observed previously and' is consistent with the theory of an intrinsic or endogenous factor Ln can cer. The only other explanation would be that the susceptible members of this age group had died earlier of lung cancer. Table 42 which ap pears later in this section indicates that the members of the cohorts did not die.from lung cancer at a younger age than the general population. The rates by weighted exposure are shown in Table 8, and it will be noted that they present strong evidence against asbestos being a carcinogenic agent. For the Asbestos cohort the rates actually de crease with increasing degree of exposure, and at Tbetiord Mines they appear completely independent of exposure, if wo count only the "proved" cases. 33 TABLE 7 Number of Persons and Number of Lung Cancer Deaths by Length of Employment t Length Asbestos Thetford Mines Combined of Lung Lung Cancer Lung Cancer Employ Cancer Deaths Deaths ment Persons Deaths Persons Proved Total Persons Proved Total 5-9 10-10 20-29 30-39 40-49 50+ Total 880 864 342 166 IT 2 Tm 0 915 0 1534 1 580 2 435 0 168 0 53 T 3Tbs 0 0 1795 0 0 1 l 2 39B l 1 2 '2 922 3 3 3 5 ` 603 5 7 0 l 185 0 1 00 35 0 0 6 9 "5958 9 77 Annual Lung Cancer Death Rates per 100,000 Man-Years of Exposure by Length of Employment Length of Emsiormeat 5-9 10-19 20-29 30-39 40-49 50 + Over-all ' Asbestos Total 0 0 49 198 0 _0 . 22 Thetford Mines Proved Total 00 11 It 57 57 US 192 0 99 00 27 41 Combined Proved Total 00 77 54 54 138 193 0 90 00 25 34 39. TABLE 8 Number of Persona and Number Of Lung Cancer Deaths by Exposure Category Exposure Category Asbestos i Thetford Mines Combined Lung Cancer Lung Cancer Cancer Deaths Deaths Persons Deaths Persons Proved Total Persons Proved Total i . 969 2 1062 2 2 2031 4 4 u 564 t 1586 2 3 2150 3 4 m 735 0 1037 2 4 1772 2 4 Unknown 5 0 00 0 5 0. 0 Total 2173 3 3655 6 9 5953 9 12 Annual Lung Cancer Death Bates per 100(000 Man-Years of Exposure by Exposure Category Exposure Category Asbestos Total 1 II . Unknown ' Over-all 34 30 0 0 22 * No one exposed Thetford Mines Proved Total 31 31 21 32 32 64 0 27 41 Combined Proved Total 33 33 23 31 19 37 00 25 34 -to IX exposure to asbestos is in any way connected to lung cancer, we would expect that the longer and heavier the exposure, the higher the rate that would be Xound. The only possible error In this Interpreta tion could occur i! the weighted exposures were inversely related to years oX employment, in which case the heaviest weighted exposure (category Ul) would show the shortest length ot employment. Tables 9, 10, and 11 which list the number oX persons in various exposure categories by length oX employment indicate that this error has not occurred. In fact, the average number of years of employment for each exposure category is almost identical. TABUS 9 Number of Persons in Various Weighted Exposure Categories by Length of Employment Asbestos Length of Emolovrr.ent Weiahted Zxuosure Categories J_ a m 5-9 10-19 ' 20.29 30.39 40-49 50 * Total Av, Yrs. of Exposure ' 429 . 273 159 98 9 2 969 15.5 213 217 89 42 3 0 564 IS. 2 239 373 92 27 4 0 735 14.5 Unknown 0 1 2 l 1 0' 5 29.0 Total 880 864 342 168 17 z 2273 IS. 1 41 TABLE 10 r Number of Persons in Various Weighted Exposure Categories by Length of Employment Thetford Mines 'Length of Employment 5-9. 10-19 20-29 30-39 40-49 50 Total Av. Yrs. of Exposure Weighted Exoosure Categories _1_ U 111 Unknown Total 279 390 155 149 67 zz 1062 19.9 385 666 274 176 64 21 1586 18. 7 251 478 151 110 37 10 1037 18. 1 0 0 0 0 0 0 0. 915 1534 580 435 168 53 3685 18. 9 TABLE 11 . Number of Persons in Various Weighted Exposure Categories by Length of Employment Combined Asbestos and Thetford Mines Length of Emolovment 5-9 10-19 20-29 . 30-39 40-49 50 t Total Av, Yrs. of Exposure Weighted Exposure Categories 1 u 111m 707 663 314 247 76 24 2031 17. 3 598 881 363 218 67 21 2150 17. 8 490 8SI 243 137 41 to 1772 16.6 Unknown 0 l 2 l 1 0 5 29.0 T1 o'tal- 1795 2398 922 603 185 55 5958 17.5 4Z. Table IZ, which develops the rates for smokers and non smokers, Is most striking. It shows that not a single case of lung cancer developed among the 1265 nonsmokers and that all cases of lung cancer, both "proved" and "suspected", occurred in smokers. A comparisonof Tables 8 and IZ certainly suggests that smoking is a greater hazard than exposure to asbestos in the mining operations. Table IZ was so striking that it was felt that further veri fication was necessary. It was possible that some abnormal distri bution may have occurred, e.g., the nonsmokers may have included a larger percentage of young men. Consequently, additional Tables, l>, 14, and 15 were constructed to show the distribution of smokers and nonsmokers by age, length of employment, and degree of exposure. Although thore ere 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.? years less than that of the nonsmokers. Table 14 shows tbai as far as length of employment is concerned, the smokers had worked about Z.3 years less on the average than the nonsmokers. With longer exposure and greater age, one would expect the nonsmoking group to show a higher rate if lung cancer were due to asbestos. . Table 15 shows that the average exposure category was al most the same for the two groups. Therefore, this variable seems to be of no importance in accounting for the difference between lung cancer death rates for smokers and nonsmokers. u. TABLE 12 Number of Persona and Number of Lung Cancer Deaths by Smoking Habits Asbestos Lung Cancer 1 Thetford Mines Lung Cancer Deaths Combined Lung Cancer Deaths Persons Deaths Persons Proved Total Persons Proved Total Smokers Nonsmokers Unknown Total 1931 340 & nn 3 0 0 1 2742 92S IB 3b8S 6 0 0 6 9 4673 9 12 0 1265 0 0 0 20 0 0 7 59S8 9 12 Annual Lung Cancer Death Rates per 100, 000 Man-Years of Exposure by Smoking Habits Smokers Noosmokers Unknown Over-ail Asbestos Total 26 0 0 IT . Thetford Mines Proved Total 36 35 00 00 IT 41 Combined Proved Total 32 43 00 00 IT 14 i TAbl.L .1 J Number of Smoker# anil Nonsmokert by Ago Croupe Age Group* 2U-4 1 45-54 55-64 tit Unknown Total Av. Age , Smoker 061 171 16] 16 0 1011 IS. 5 Asbestos Wn-o--n--*----- U.ni.1 iiuoker known 11Q 1 75 ' 1 It 0 10 00 1-10 J JU. 1 41.0 TkeUord Mines ----------------- "tNito-n--------------Un-n--*-- Smoker smoker known IOJ? 1*17 11 675 U7 ) 210 ISO 2 wu 147 1 2 01 2742 V25 IS IV. 8 46.4 40.7 - Smoker 3200 896 411 164 2 467) 19.) Combined Woo* On- muher known 68V 12 224 1 202 2 150 1 01 1266 20 44.2 40.7 I'crccnlogc Distribution of Smokers and Nontmokcra by Age Groups Ago Croups Smoker Atbeefos Non Un smoker known Thctford MinesCombined ' Non Un Non Un Smoker smoker known Smokor smoker known 20-44 46-64 66-64 66t Unknown Twi#l 70.5 19.2 e.4 1.7 .0 1110% 70.6 22.0 6.5 .V .0 looy. 50.0 so.o .0 .0 .(i limy. 67.1 19.1 v.n 4.7 .1 Too* 4B.5 16. 1 19.5 15.9 .0 luoy.' 61.1 16.7 II.0 5.6 5.6 lOO* '66.9 IV. 2 8.8 1.5 "Too* 54.5 17.7 16.0 II.8 . (1 Mm/, 60.0 20.0 IU.0 5.0 s.u 1 Oil n J.ess Ilin 0$7* TADm 14 Number ol Smoker. and Nongmokcre by l.cnuili ol Cmploynrcni * Unijlli of L'mpluy Asbestos Nun* ' Un- muni Smnkur omiihor known 5-9 1 D. 1 9 720 ISO 740 IN i 1 20-29 296 46 0 )0-)9 40.49 I4B 20 0 lb 1 0 5U 2 n a Total mi )40 I Av. I.cngth IS.1 vf kJi)|ilov* 1). 9 ll.O mvnl Thclforri Mined Non- Un* Smoker smnkur known 680 210 9 1210 112 ) 426 IS) 2 2 8S 146 4 94 74 0 )l 22 0 2742 925 18 ID. 1 21. ) 16.6 Combined Non- Un- Smoker dmukcr known 1408 377 to 1967 426 4 722 199 2 4)) 166 4 110 75 0 )) 22 0 467) .. 1265 20 17.0 IV.) 16. 0 PerccoUgu Distribution of Smokers <ml Nonsmokcra by Ucn>th of Employment l.ungili of Employ* incut 5-9 10-14 20-24 20-34 411.49 sm Tol.il Aviivaio* Non Smoker UMOker J7. J 76.8 )K.d )).S IS.) n.s 7.7 s.o . ti . J . 1 .0 100% 10(1% Unknown so.o so.o .0 .0 .0 .0 100% ThelforJ Mint'd Non* Un- Smoker smnkur known 26. 1 23.6 so.o 44. 4 )). 7 16.7 IS.6 16.S II. 1 10.4 IS. 8 22.2 )* 4 9.0 .0 l.t 2.4 .0 100% 100% 100% Combined Non- Smoker smoker )0. 1 24.8 42.1 )). 7 IS.4 15.7 9. 1 1). 1 2.4 5.9 . 7 1.0 100% 100% Unknown so.o 20.0 10.0 20.0 .0 . 100% TAin.tr. is Number of Smokers and Nonomokor# toy poure Category Ailioaioa L'lputuro Nuik Smulir tuhbwr 1 mo ISO n 40) in 614 Unknown 4 Total THT Av. L`i|o*m ft 1.9 Category 0(1 101 1 m l.u Unkotow it 1 1 0 0 T I.S Ttieifiml Mine Nun* (J. Smiikwr tfiitnkur Imhiwm 7 of lib 3 uoo 372 b 771 M 00 1 0 Tfor "of? Til 2.0 1.9 2.1 Ciiinhlncrt Non- Un- Snnikr Oiitnkor l lIlllMI 1993 070 i 1691 092 7 1029 11U *) 41 TSTT TTET 0 To 2.0 1.9 2.3 rtriciiUyc DUlI'tlmlioi* ul Smoker* dud Nouamukere by Kipositrc Category bli fiuauftf Caugorg 1 II III Unknown Tut at Asliealea Nun* Smnfccr omnkcr 42.0 H.9 29.0 21.9 1 1.0 29.7 .1 tuliy. .1 TUSlb Un- known 90.0 90.0 .0 .o Tooil Yliulfofil Mince Nun- Ul.. Smoker eiimker known 27. 1 11.2 lb,7 0 1.0 00.2 33. 1 29. b SO. 0 .0 Toff?. -0 Tuojl .a iooH Comiilncil Nun- Smoker emnkcr 31.2 17.5 3 b.2 19.7 30.9 2b.7 0. 1 IUO-?. n. i 1011% Unknown 20.0 39.0 09.0 .0 1OU V. 47. The result of this additional analysis is chat none of 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. Asbestosis and Lung Cancer When we attempt to relate the lung cancer deaths occurring in the cohort with the reported cases of asbestosis, we are 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 i.- w (133) (135) (147) (154) (195) ' one stuay, as high as 87 y*. However, data on cases of asbestosis from the cohorts at Thetford Mines and Asbestos pro duce a rate of only about 5 7-. It is true that these data are based on only those cases 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 lung tissue. As a matter of fact, Dr, Cartier has estimated that there are probably 300 workers who do not show radiological evidence of asbestosis, but-who have some'degree oi fibrosis. He also estimates that there are perhaps 40 workers who may have died or retired with this disease. Instead of 143 cases of asbestosis in the whole working force at Thetford Mines, we should then have perhaps 500, but even this would result in an over-all rate of less than 107*, which is far below those widely reported. In our 48 combined cohort, there are 1765 men who have had more than 20 years of employment, and 411 of these have worked in the heaviest average exposure. According to the records, we can account for only 138 cases of asbestosis in the combined cohorts. If even 25% 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 thi9 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 as showing fibrosis. Cases of asbestosis which were accumulated from the au topsy records and from the periodical physical examinations result in a distribution which is shown in Table 16. TABLE 16 Distribution of Recorded Asbestosis Cases In Cohort Living Dead Total Asbestos 18 4 22 Thetford 86 30 116 Combined 104 34 . 138 TABLE IT -Part I Number of Asbestosis Cases By Length of Employment and Exposure Category Asbestos . .Length of Employment Less than 10 10-19 20-29 30-39 40-49 50 + Total Av, Yrs. of ' Employment Exposure Category I K_ lil 0 0 2 0 0 0 2 . 25 0 1 7 ' 1. 00 9 25 0 2 4 4 1 0 11 29 Unknown 0 0 0 0 0 0 0 Total 0 3 13 5 1 0 22 27 Percentages of Asbestosis Cases By Length of Employment and Exposure Category Length of Employment Less than 10 10-19 20-29 30-39 40-49 50 + Over-all Exposure Category _U_ III a 0 1.3 0 0 .0 .2 0 .5 7.9 2.4 0 1.6 0 .5 4. 3 14.8 25.0 1.5 * No one exposed In this group Unknown 0 0 6 0 ~o Total 0 .3 3. 8 3. 0 5. ? 0 1.0 SI fABLE 17- Part III Number of As'oestosis Cases By Length of Employment and Exposure Category Asbestos and Thetford Mines Combined Length of Emolovment Less than-10 10-19 20-29 30-39 40-49 50 + Total Av. Yrs. of Employment Exoosure Category I 11 LU 00 0 02 9 4 (2 25 2 16 ' 37 0 6. 21 02 2 6 39 94 28 33 33 Unknown 0 0 0 0 0 0 0 Tota 0 11 41 55 27 4 138 33 Percentages of Asbestosis Cases By Length of Employment and Exposure Category Length of Employment Exoosure 'Cateq ory j. _U m Less than 10 10-19 20-29 30-39 40-4950 + Over-all- 0. 0 l;3 .9 0 0 .3 0 .2 3. 3 7.3 9.0 9. 5 i. a 0 1.0 10. 3 51.2 20. 0 5. 3 No one exposed in this group M O Unknown 0 0 0 0 0 Total 0 .5 4. 4 9. 1 14.6 7. 3 2.0 52 A percentage incidence of asbestosis for each exposure category has been developed as well as for each period of employ ment. This information is shown in Table 17. It will oe noted that within an exposure category, the incidence rises with increased length of employment. It is also apparent that the incidences, even in the category of heaviest ex posure, are far below the rates found by the authors previously re ferred to. It seems clear, that unless concentrations of asbestos dust to which the miners are exposed are very much lower than those which obtain in ail the other studies, there has been a gross under reporting of the asbestosis cases. The obvious result is a higher relative frequency of lung cancer in association with asbestosis, ' Table 18 compares deaths-due to lung cancer and fatal cases with as bestosis. alone and in combination with each other. TABUS 18 - Part 1 Statistical Analysis of the Causes of Death Asbestos Cause * Asbestosis No Asbestosis Total Percentage Lung Cancer 1 ( .2) 2 ( 2.3) 3 6. I No Lung Cancer 3 (3.3) 43(42.2) 46 93.4 Total 4 45 49 Percentage 8.2 91.8 Figures in parenthesia are the "expected" numbers 53 TABLE 18 - Part U Statistical Analysis of the Causes of Death Thetford Mines Cause Asbestosis No Asbestosis Total Percentage Lung Cancer No Lung Cancer Total ' Percentage 3 ( 1.3) 25(26.71 28 21.2 3 ( 4.7) 101(99.3) 104 78.8 6 126 132 4.5 95.5 Figures in parenthesis are the "expected" numbers TABLE 13 - Part III Statistical Analysis of the Causes pi Death Asbestos and Tbetford Mines Combined Cause Asbestosis No Asbestosis Total Percentage Lung Cancer No Lung Cancer Total Percentage 4( 1.6) _23(30,4) 32 17.7 5( 7.4) 144 (141.6) 149 82.3 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 in the combined cohorts. This difference is significant at the 95% level using the chisquare test of significance. The importance of the under-reporting of asbestosis can be observed in Table 19.' . 54 ' TABLE 19 Statistical Analysis of the Causes ot Death if 20 Nonasbestosis Cases had been Diagnosed as Asbestosis Cases Cause Asbestosis Mo Asbestosis Total Percentage Lung Cancer Mo Lung Cancer Total Percentage 4( 2.6) .48(49.4) 52 23.7 5( 6.4) Jj!4(lZ2.6) 129 71.3 9 ,172 18L 5.0 95,0 Figures is parenthesis are the "expected" nuzsbers Is this table, it has been assumed that 20 of the cases which did not have lung cancer and which were reported to have na asbestosis cid, in fact, have asbestosis, the diagnosis of which, was missed. Althougn the cases of lung cancer with asbestosis are still higher than would be expected, the difference is no longer significant at the 95 ft 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 had 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 stressed because it seems so obvious that in under reporting, asbestosis the relationship between it and lung cancer baa been made to appear more significant than it probably is. 55. Four of the proved cases of lung cancer and one of the suspected were associated with asbestosis. Since we have only 32 deaths in which asbestosis.was present according to the records, the incidence in this series is 12.5%. wnile this is slightly lower than the rates found by Merewether, Cloyne, and Wedier, it is still much higher than could be expected if the asbeetosis incidence were anywhere near the experience reported by other authors. Con*.e>Tiaon of the Cohort Experience with that of the Province of Quebec, Porctaion of Canada, and the United States - In order to make a comparison of the experience among asbestos miners with that of the general population of the Province of Quebec, statistics were gathered, as stated earlier, in the offica of the Division of Demography in the Provincial Ministry of Health. The data on total deaths, deaths from all forms of cancer, and deaths from cancer of the lung were obtained hy sex and by county for the years 1950 through 19SS. 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 deaths from lung cancer in the Province and In the two cohorts for the years 1950 through 1955, and shows the annual rate per 100,000 in those segments, So. It will be noted from the table that the mortality rate for the Asbestos cohort is almost exactly the same as that for the Province, while the rate for "proved" cases in the Thetford Mines cohort is only 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 does not exceed the significant level. One further Interesting observation from Table 20 is the rather marked increase in the total cumber of cases for the Province . between 1950 and 1955. It is assumed that at least part of this increase Is due to improved recognition and reporting of lung cancer during the interval. Pot this reason, the years 1954 and 1955 ware thougoc to be more nearly representative of actual conditions. .Sven 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 would appear to be substantiated by the fact that the reporting of cases in the combined cohort showed no such increase over the same period. ' Table 21 was compiled to show the annual age-specific lung cancer rate of cases in which the death certificate merely read "cancer of the lung", as distinguished from those in which the diagnosis was TAIII.B 20 Comparison ol Province of Quebec with Aebceloe and Thetford Mines Province Aobeetoe Cohort Total Proved Thetford Mince Cohort Total Proved Province, excluding Asbestos Workers No, of Porstuio 1,198,000* 8.261 1 3,668 1, 198,000 I960 196 l.nnft Cuncer Dealhi 1951 -T95Z^ l9Sl " I-J44 280 29$ 303 303 01 D' 00 00 0 0 31 11 03 02 3 1 193 810 24$ 300 308 1955 357 Tool Annual Hale per mo.ono >624 22,6 2 3 22. 1 2 3 22.1 1 9 41.0 1 6 27.3 354 161! 22.5 In the Province figures, ll liae been assumed ell male lung cancer deaths are for men of 20 years, * Approximate mid.point of the enumerated population for 1051, and the estimated population (or 1954. (Hiipporl, Dlv.'dc la Ocmogtuphle) t Number alive In cohort at beginning of I9S2, 53 confirmed by autopsy, surgery, or biopsy. The term "specified primary" refers to those cases in. these same two categories in which the tumor was .specified as having originated is the lung, it will be noted that, of the total cases certified in 1955, a much higher percentage than in 1954 was specified as primary. The table also shows that a higher percentage of the total cases certified in 1955 were proved, again indicating increasing interest in this disease. A comparison has been made between the age-specific rates shown in Table 21, and those for the cohort shown in 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, summarized in Table 22, shows that the observed number of deaths in our sample is not significantly greater than the expected number of deaths, based on the average of the 1954 and 1955 figures for the Province. It is true that, in the case of the age group of 65 and over, the five deaths provide a figure which is al most significant at the 95% level. However, it should be noted that this number includes one of the suspected but unproved cases previously referred to. Furthermore, it is rather likely that the rate for the gen eral population is understated in this age group, for the obvious reason Chat the exact cause of death in the very old is not a matter of the same intensity of interest xa it is in younger persons. 59 Before leaving this comparison of the Province with the miners, it should be shown that.their age distributions are reasonably the same. That this is the case can be observed from the following tabulation: Age Distribution of Adult Males for the Province of Quebec, 1951 (Rapport, 1954) Age Group 20-44 45-54 55-64 6$ * Total Number 727,135 188,952 128,944 113.467 1, 158,498 Percentage 63 16 11 10 100 Percentage Combined Cohorts 66 ' 19 10 5 100 It should be remembered that the miners retire and 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 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 mincra. 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. taui.u 21 A|e Croup l.tutg Cancer Deaths lor lbs Province of Uiieliec (t)j|a from Death Cociideblcs) Cstiioaleti * lbi|itilali<m I ;S4 Total Certified Total Proved Specified Printer y Total Proved l*?5S Tout Certified Tot a 1 Proved Specified Primary Total Proved 0.44 45-54 55-64 65 Total 777.000 202. 000 117,000 121.000 1,217,000 17 6/ itio 111' 275 ii 16 38 11 120 ti 9 17 ') o 27 60 IS 6V 11 117 57 HI 21 148 5-1 171 77 . 342 ISS 17 >) 56 32 116 57 148 5-1 137 152 Cellmate for population obtained by applying 1 VS I percentage* for ago groups for male* to the total population for IV54, as given In Happorl, Dly. du U Demographic. A|*e Croup 20-44 45-54 55-64 ts I Over-all Annual l.ung Cancer Death Kate* per 100,000 1754 Total . Certified Total Proved S|>ccirtuti i* runary Total Proved 2.2 33.2 71.0 71.7 21. 8 1.7 17.8 27.7 27.1 7.7 1.4 11.3 SO.4 56.2 IS. 4 ` 1.2 14.4 23.d 21.0 M 175 5 Total Ceri iflotl Tol al Proved Specified Primary Total Proved 2.2 29.7 HS. 1 122. 3 27.6 1.2 17.3 41.6 44.6 12.5 2.2 27.7 84.7 122.) 27.2 1.2 15.8 41.6 44.6 12. 3 61 TABLE 22 Comparison of the Actual and Expected Numbtr of Lung Cancer Deaths by Age Among Asbestos Miners Age Grouo Province Total Specified Primary Rate oer 100,000 No. of Miners Expected"*No. of Deaths Observed No, of Deaths Proved Total 20-44 45-54 55-64 65 4 Unknown 1.6 24.3 67.6 89.3 3901 1124 615 315 '3 0* 2 2 2 11 13 33 45 00 * Actually , 4 '+ The expected number is based on the average o the 1954 and 1955 age-specific rates for the Province of Quebec. Table 22 also answers a question previously raised. It shows that the members of these cohorts have not died from lung can- . ccr at an age earlier than the general population, and that such an ex planation cannot be offered for the absence of lung cancer in 240 men with more than 40 years of employment referred to on page 37. A comparison between the asbestos miners and the popu lation o the Dominion as a whole was made, using statistical material from several sources. In one source, Phillips gave age- and sex- specific rates for Canada for three periods between 1931 and 1952. The rates for males are given in Table 23. 62. TABLS 23 Annual Death Rates per 100,000 for Cancer of.the Lung in Canada* Age Grouss 1931-1933 Crouos of Years 1941-1943 1950-1952 Under 30 30-34 35-39' 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 8S + All Ages 0.2 0.9 2.0 3.0 5.2 8.2 12. 7 12.5 15.1 10.7 15.3 B.2 11.4 2.3 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 t.O 0.8 3.0 6.5 16.7 37. Z 59. 7 77.8 102.9 86. 3 83.9 59. 7 71.0 15.8 * "Mortality from Lung Cancer in Canada", 1931 to 1952. These figures show strikingly the increase in 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 these figures for purposes of comparison, it is necessary to combine the rates for certain, age groups in order to conform to the age distributions used in this study. Since the exact populations in each age group for the years indicated is not loiown, 63 this must be an approximation. However, the rates would be some* what as follows: Age Crouo 20-44 45-54 55-64 65 + Rate 5 27 69 90-95 These rates are, is general, lower tbas those developed for the total (proved and suspected) cases of lung cancer among the asbestos miners. The only large difference, however, is ir. the age* group of 65 years and over, and it is quite possible that the rate for this group may have increased for Canada between 1952 and 1954 as it did for the Province of Quebec. (See Table 21) A further comparison has been made with an over *all rate obtained from the American Cancer Society for respiratory can* cer deaths in Canada in 1953. This rate, for males, is 20. 3 per 100,000, an increase of 5 per 100,000 over Phillips' 1950-1952 rate, and compares with 2S.5 per 100,000 for proved cases and 34,0 per 100, 000 for total cases among the asbestos miners in this study. It is therefore obvious that there are no important differences between the rates for asbestos miners and those for tbe general population of Quebec and the Dominion of Canada. . Since it is probable that figures for the United States are more complete and, therefore, pooaibly more comparable to tbe data for tbe miners, age-specific rates were computed from "Vital Statis tics of the United States", Volumes I and 1J, for 1952. These rates have been tabulated in Table 24, TABL 24 Number of Deaths and Death Bates per 100,000 by Age Groups for the Adult Male Population of the United States---Data Prom "Vital Statistics of the United States", Volumes I and U, 1952 Age Grou? 20-44 45-54 55-64 09 4 Total Population 24,544,000 8,065,000 6,340.000 5.670, 000 44,619,000 Case s 883 2979 6254 64 83 16,599 Bate oer 100. 000 3. 6 36.9 98.6 114.3 37.2 ' It is apparem that these rates compare favorably with those for the asbestos miners as shown in Table 6. Still other rates for the United States were obtained from the American Cancer 5ociety, and for males, these were 25. 5 per 100, 000 in 1953, end 28. 0 per 100, 000 in 1955. They are not identical with the rate calculated from the figures of the office of Vital Statistics, but this is possibly because the American Cancer Society rates are for males of all ages. Nevertheless, they, too, compare favorably with the rates of 25 (or 34 for total cases) obtaining among tbe asbestos miners. 65. . Returning to a comparison between the asbestos miners and persons who are exposed to asbestos in one form or another (as distinguished from the general population groups ;ust discussed, who have no exposure) an interesting observation can be developed by de- (12Z) duct ion. Hueper has stated that there are about 35,000 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 between 3, 000 and 5, 000. With workers in Africa, Denmark, Norway, and other countries, at least 50,000 persons must be exposed throughout the world, and it can be assumed that this number has been fairly constant in the 20 years ' since 1935 when the first case of asbestosis with lung cancer was re ported. At least a million man-years of exposure has thus been accumu lated, and this figure can be divided by the approximately ISO cases of lung cancer with asbestosis repo'rted during the 20-year period. This gives a rate of 15 per 100,000 which is at least indicative that any lung cancer rate which can be calculated for workers exposed to asbestos dust is not much greater than that for the unexposed persons. Comparison 3erween Right Counties Adjacent to che Asbestos-Producing Areal a.-.c ;?*.; Selectee Counties To compare lung cancer mortality races in the coun ties surrounding the asbestos-producing areas wich another group of counties in which no asbestos miners are likely to reside, the rates were computed on the basis of figures for the years 1950 through 1955. The eight counties selected for comparison were Argenteuil, Chateaugay, Mor.tmagny, Portneuf, Richlieu, Rlvieredu-Loup, St. Hyacinthe, and 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 Arthabaska, 3cauce, Drummond, Frontecac, Megantic, Richmond, Sherbrooke, and Wolfe. Table 25 shows the number of lung cancer deaths for che years 1950 through 1955 for each of these counties, and a mortality rate, based on the adult male population in 1952. To emphasize the comparison Megantic County has been shown separately, as has the Province of Quebec and also the Pro vince with the eight "asbestos-producing" counties subtracted. Be cause of its unique lung ciactr death rate, Montreal el Isle de Jesus has also been listed In order to provide further comparison. TABLE 25 Humber of Ung Cancer Deaths am) Mate per 100,000 Mon-Years Counties Mcgantlc County Eight "Adjacent*1 Counllc. Eight Selected Counties Province of Quebec Province of Quebec lees Eight "Adjacent** Counties Montreal ct late de Jeaua Adult Mate Population 1051 . Mate l.ung Cancer Deaths* 1950 1951 I95Z 1951 1954 1955 Total Rale per too. 000 11,100 31 3 11 4 15 IB.9 97,600 63 9 16 4 16 54 9.4 8), 000 Z to 4 18 5 9 49 9.8 1,198,000 196 zzo Z4S 301 101 157 1624 22.6 1,100,000 194.000 190 ZI7 37 216 IS8 287 299 192 185 141 1470 225 T70 21, 8 12.1 Jt Is assumed that all male lung cancer deaths occurred after ige 20, 68 It is apparent from the table that the lung cancer death rate for the eight counties Immediately surrounding the asbestosproduciag areas is practically identical with that of eight counties selected for comparison. While Megantic County has a rate nearly twice that of the combined eight selected counties, it is lower than the rate for the Province, and considerably lower than the rate for Montreal. The figure for Montreal would certainly be higher except for the very low numbers of deaths reported for 1950 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 nO 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 AU Recorded Lung Cancer Cases, Living, and Dead, at A.- -..stos and Thetlord Mines Although a simple enumeration of all tbe known or sus pected cases of cancer of the lung In these areas has no particular value from a statistical point of view, it is of interest to summarise 69. such cases for the record. There were nine deaths prior to the be* ginning of the time period covered by the study, including one in which the diagnosis was mediastinal lymphosarcoma. All of these nine cases occurred at Thetford Mines. It is somewhat surprising that there is ao record of any lung cancer deaths among the Asbestos group in the interval preceding the beginning of the study and equally so that ao cases have been reported in 19S6 and 1957. During the period covered by this investigation, there were six proved cases and three suspected cases at Thetford Mines, as well as three proved cases at Asbestos. Through 1956 and to dato in 1957, there were eight deaths at Thetford Mines, six of which were merely suspected and included such diagnoses as mediastinal lymphosarcoma, mesothe lioma, cancer of the leg with metastases to lung, absess of lung, and cancer of the pancreas. One other was diagnosed on the basis of x-ray only. In addition, there are now Living four eases in which the diagnostic evidence is strongly suggestive of lung cancer. This is a total of 33 cases of all types, including ten "suspected" but unproved cases, and four that are still living. The remaining 19 constitute the total of proved cases of cancer of the lung in both areas since 1940. Sixteen of these have been at Thetford MLnea and only three at Asbestos, all of which occurred during the period oi the study. The proved caees averaged 59 years of age at death, and varied between 37 years and 68 years. Their working span covered i 70. periods varying between a minimum of 14 years and maximum of 37 years. Only three men had less than 25 years of employment in the industry. Seven among those on whom such information is available had a weighted exposure placing them in category III, and six worked in an exposure represented by category I. Although they were subjected to post-mortem examination, there were three among these proved lung cancer cases in which we do not have information regarding the presence of asbestosis. Of the remaining 17, asbestosis vis present La nine, although it was minimal in two, and two pathologists disagreed regarding its presence in one. Eight of the proved lung cancers, therefore, were not accompanied by aabosiosis. VI. SUMMARY AMO CONCLUSIONS Interest in the question of whether there may be an as sociation between lung cancer and asbestosis or exposure to asbes tos has been evident since the report in 1935 by Lynch and Smith of a case in which lung cancer and asbestosis were both present. As additional cases in which the two diseases coexisted were reported, a causal association appears to have been gradually accepted by many authors, although a few workers considered the correlation to be in conclusive. Cases of lung cancer which had occurred among the as bestos miners in Quebec had 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. ' . Reference to the Literature shows a remarkable uniformity both of method and of conclusions. In general, the method has been to study a circumscribed series 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 the total number has served as the denominator by which the number of lung-cancer cases is divided to produce a certain "incidence rate". This rate, as reported by various authors has been consistently high, and its uniformity is indicated by the following tabulation. 72 Author Merewether Wedler Wyers Lynch U Cannon Glovne Totals Asbestosis Deaths 344 92 115 40 121 712 Cancer of Lung 55 13 17 3 17 107 Percentage Incidence 16.0 16.3 14.8 7.5 14.1 15.0 The notable characteristic of all previous publications is the adherence to the development of a percentage relationship in (63) a relatively small and very selected group of cases. Only Doll, among all of these authors, has described a representative population group and studied it for the mortality rate from lung cancer and com pared this rate with that for a control group. His investigation dealt with only 113 men in the study population. Since most earlier studies had been limited to enumerating the lung cancers found in certain selected samples, such as cases coming to autopsy or death certificates in which asbestosis was men tioned. it was apparent that they could not fulfill the requirements of an epidemiological and statistical approach to the problem. The pre sent study was, therefore, designed to meet the requirements of this method. After a preliminary survey to explore the availability of reliable information, data were gathered on workers in the asbestos mines in Quebec, based on medical records at the two main locations 73. of these operations. Cohorts were defined according to certain cri teria and ail workers who met these criteria were included In the stud/. Through their medical records, data relative to their charac teristics were collected and their status at the end of a six-year period o'f 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 lung cancer for the general population of the Province of Quebec and its various counties and for the Dominion of Canada, as well as the United States were calculated from statistics collected in the appropriate places. Comparisons of the rates obtained for asbestos workers and for the other population groups were made according to accepted statistical methods which have been explained in some detail in section IV. Records 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 187 known dead, cancer of the lung was considered to have been reasonably proved in nine and to be strongly suggested in three. The members of the cohorts were studied with respect to age, length of employment, a weighted average of their exposure, and their smoking habits. Four thousand, six hundred and seventy-three 74 were found to be smokers w train the definition of that terra as used in this study. Thirty-four percent of the cohort were more than 45 years of age, and 30% had been employed for longer than 20 years. Thirty percent had a weighted exposure which placed them in cate gory III. The mortality rates for lung cancer, as computed on the basis of six "proved" deaths among the Thetford Mines cohort and three "proved" deaths among the Asbestos cohort, were 27.6 per 100,000 for the Thetford Mines group, and 22.2 per 100,000 for the Asbestos group.' When the three "suspected" cases were added, the "total" rate for the Thetford Mines cohort rose to 41,3. The rate for the combined cohort was 25.5 per 100, 000 for "proved" cases, and 34 per l<70, 000 for "proved" and "suspected" cases. The importance of the suspected but unproved cases in determining these rates has been reiterated be cause it is likely that such cases wo.uid not be included in the statistics for the general population. According to the findings in this study, the mortality rate from lung cancer does not appear to Increase with length of exposure or with degree of exposure, a fact which presents strong evidence a gainst the carcinogenicity of asbestos. On tho other hand, the study indicates that cigarette smoking is a very important factor in 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 75. under-reporting of asbestosis cases. The incidence of aabestoais indicated by the medical records is far below that which would be expected on the basis of all previously published figures. Naturally, when the cases 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 7* of the recorded cases of aabestoais in this study developed lung cancer, a figure slightly lower than those quoted by 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 observed number of deaths among ehe 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 100,000 for the rest of the Province, and 20,8 per 100,000 for adult males throughout the Dominion-of Canada. It also compares 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 roost of the asbestos miners live, have almost identical mortality rates with those of eight counties widely scattered 76. through the Province, and are lower than those (or the remainder of the Province, and much lower than the rate for Montreal. Since 1940, there have been 19 cases In which the diag nosis of primary cancer of the lung may be considered to have been proved. Approximately half of these cases were associated with asbestosis. All but one died in the recognised "cancer age" and at least one-third'had only the lightest exposure (category I) to asbestos dust. Conclusions On the basis of a careful and detailed study of what are believed to be complete and reliable data, it seems fair to.conclude that the asbestos miners at Thetford Mines and Asbestos in the Pro vince of Quebec do not have a significantly higher death rate from lung cancer than do comparable segments of the general population. Despitd this, the results suggest that a miner who develops the disease asbestosis does have a greater likelihood of developing cancer of the lung than a person without this disease. We suspect, however, that under reporting of asbestosls cases had led to a fallacious finding In this con nection. The death rate from lung cancer in the areas continguous to the asbestos operations Is comparable to that in areas widely scattered throughout the Province of Quebec and is tower than in some urbanized areas within the Province. The value of this investigation would be considerably en hanced by continuing the observation of the cohorts formulated herein on a year-by-year basis. It is strongly recommended that Che chest x-rays of all workers be submitted to an independent reading for the . diagnosis ai asbestosis, since an inaccurately iow incidence rate for this disease creates an artifically high relative incidence for lung cancer. -78; VII. BIBLIOGRAPHY 1. Adler, I. Primary malignant growths of the lungs and . bronchi. London, Longmans, Green !e Co., 1912, p. 39. 2; Alascio, Escobar R. Bronchial carcinoma; review of two hundred cases. J. Internal. Coll. Surgeons. 26: 375-379, September, 1956. 3. Allen, M.L. 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