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FILE NAME Industrial Hygiene Foundation IHF DATE 1957 Sept DOC IHF041 DOCUMENT DESCRIPTION Report - An Epidemiological Study of Lung Cancer in Asbestos Miners ae whee fa bo Bad CM weep owes hr ee aed 3 saa a eeu. sae=u writer,Tt. . ted?Yeet A) uaat orei, hag .' wee re i a OR Se + mee Comme cn TU Pe RIP MII Pte eee, ome awe ss see . SS is = 2B,ea F_ rv - So. rs a8 ok Sr NeRSENS cee tee eee Fee weme. ee ree. ee We oom tm er mmc ee ee oe w ee ees teen ve Mt mies , eto Medemtcn a ethicost Ds EBONY Anat aM nme bmi : oSANEPIDEMIOLOGICAL STUDY OF eas LUNG CANCER mar wt te. IN . . a . a al wt ree oe gee ee ES . wee oe . . : Lee ASBESTOS . . MINERS woe ove. . . a eo tas ak re <0 oa a 5 >a . Hoe ewe . - re Cae, Set mn Report to ; QUEBEC ASBESTOS MINING ASSOCIATION ; . Quebec Canada identification | PLAINTIFF September 1957 ages @ : Industrial America es > PAs Hygiene Foundation of . 4400 Fifth Avenue Inc. Pittsburgh13 Pa AN EPIDEMIOLOGICAL STUDY OF LUNG CANCER IN ASBESTOS MINERS For QUEBEC ASBESTOS MINING ASSOCIATION Quebec Canada July 1956 to July 1957 By ' Daniel C. Braun M. Medical Director September 1957 By C. Richard Walmer M.D. Managing Director OT annie tees TABLE OF CONTENTS Foreword , . Glossary ....., I. I. Introduction ....4..048. I. I. Critical Review of Literature . 6 III Principles of the Epidemiological Method . IV Collection and Analysis of Data V. Results and Interpretation . . . Asbestosis and Lung Cancer . ..... Comparison of the Cohort Experience with that of the Province of Quebec Dominion of Canada and the United States Comparison Between Eight Counties Adjacent to the Producing Areas and Eight Selected Counties . . Discussion of All Recorded Lung Cancer Cases Living and Dead at Asbestos and Thetford Mines . 2... 2... VI Summary and Conclusions ..... VII Bibliography ......, : page 55 55 66 66 FOREWORD The success of a study of the type herein reported de- pends very greatly upon the availability of data from many sources and the assistance and cooperation of those in possession of these data Industrial Hygiene Foundation was fortunate in having the wholehearted cooperation of the asbestos producing companies and particularly of their medical and nursing personnel who have the re- sponsibility for maintaining the medical records of the workers In this connection we are especially indebted to Dr. Paul Cartier and his staff at the Thetford Industrial Clinic and to Dr. 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- from operation 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 * cooperation was rendered by Messrs Hardy and Hopkins of the 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 Asbestos Valuable suggestions for the conduct of the study were made by Dr. J. A. Vidal Chairman of the Silicosis Board and Dr. Guy Pathologist for the Board as well as Dr. Gregoire Deputy Min- ister of Health for the Province of Quebec and Drs Simard Dufresne and Groulx in Montreal Statistics for the mortality rates for the Dominion of Canada were obtained through the kindness of Dr. Dean F. Davies Administra- tor for Research on Lung Cancer for the American Cancer Society and those for the United States were graciously furnished by Miss Guralnick in the National Office of Vital Statistics Department of Health Education and Welfare of the United States Government Finally Finally the very great assistance rendered by Dr. Kenneth W. Smith Medical Director of Johns- Manville 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 a unique among the reported studies of lung cancer as related to asbestosis and exposure to asbestos Assistance in planning the study in such way as yae hehe 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 Pittsburgh and staff of the Industrial Hygiene Foundation The report is believetdo present the findings in an objec- tive manner and is respectfully submitted for the consideration of the Association GLOSSARY For the purpose of clarity and uniformity the terms used in this report are herewith defined according to the mammer - of their use Asbestos workers Workers exposed to asbestos dust in other than mining operations Asbestos miners Asbestosis Cohort Workers engaged in the mining and preparation of asbestos in the areas under study A generalized fibrosis of the lungs diagnosable by ray or by microscopic examination of the lung tissue but not necessarily accompanied by symptoms or by disability A segment of the population defined according to certain criteria and representative c^> the whole population Specifically in this study a group of asbestos miners having at least five years of exposure in the industry and who were in the industry during 1950 Lung cancer cancer of the lung A neoplasm of the lung or bronchus ever situated and including adenocarcinoma squamous cell and undifferentiated or oat cancer histological cell histological of the lung means means types such a Primary neoplasm originating in the lung and not secondarily Smoker As used in this presentation the term smoker refers to a cigarette smoker habitually smok- : ing more than 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 the incidence of lung cancer among males became apparent there have been attempts to associate it with one or another of the various elements in the en- vironment of man The approach used by some workers has been to suspect or one several substances and then set about in an intensive search for lung cancer among persons who have had any exposure to connection 132 those compounds In this Smith writes The ten- authors dency of 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 this this way that re- ports of the simultaneous occurrence of lung cancer and asbestosis be- gan to accumulate after the the of report of a case by LynchLynch and and Smith Smith 139 in 1935. in and in Within the next ten years about 1946 Merewether 155 reviewed reviewed 15 additional cases were reported all deaths from asbestosis asbestosis asbestosis re- corded in England since March 1924. Lung cancer occurred according to Merewether in 13.2 of these cases Continuing this study to include December 1954 Merewether counted 55 cases of cancer of the lung among 344 cases of asbestosis raising the incidence to % 92 Gloyne is whose work is also frequently referred referred to as establishing establishing a connection between asbestosis and cancer of the lung reported in 1951 the results of his findings on 1205 autopsied cases This series included 132 asbestos workers of whom 121 showed asbestosis Cancer of the lung was present in 14.1 % of these asbestosis cases In 1941 Nordmann and Sorge ( 161 claimed have produced lung cancer in mice which they exposed to asbestos dust Since 1951 additional cases of cancer of the lung coexisting with with asbestosis asbestosis have been reported and according Hueper according ( to Hueper 122 122 about 100 such cases had been reported up to 1955. As 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 c^ the lung 205 in Werber in 1952 stated categorically that in % to 17 of cases of asbestosis after a latent period of about 1/2 to 20 years carcinoma becomes established in the lung On the other hand not all tion without reservation 177 1177 7177 7 Saupe authors accepted the in 1939 had reported alleged associa- that he had discovered no cases of lung cancer among 620 cases of asbestosis which he had examined and in 1942 Angrist 104 Holleb and Angrist expressed the opinion that the number of cases of asbestosis with lung cancer watoo small for statistical evaluation In 1947 Wegelius ( 200 reported 125 radiologically diagnosed cases of asbestosis among 476 workers in Finland and found no cases of lung cancer in this group Goldblatt Goldblatt and in their section of Merewether's latest book 95 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 carcinogen There is no reliable criterion by which one can anticipate carcinogenicity and as is well chemical known relatively minute changes in the structure of a car- cinogen are sufficient to diminish or eliminate carcinogenic action is If asbestos indeed to be regarded as a carcinogen the need is felt to demonstrate some property which can be regarded as something more than inermess These authors advance the theory that until some more the. experimental evidence of direct carcinogenesis by asbestos or a decomposition product of it can be obtained asbestosmightmight be considered as a carcinogen which only induces a further development of a preneoplastic condition brought about by something independent of the asbestos 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 is perhaps more confusing than enlightening - i Meanwhile the Canadian Manville Company in Asbestos has been alert to the whole problem and at the Thetford Industrial Clinic Dr. Paul Cartier was studying the situation among a working population of about 6000 and made notable contri- butions to the literature just cited 42-44 Between these two areas a number of cases had been recognized and tabulated by the spring of 1956. At this time at the suggestion of Dr. Kenneth W. Smith Medical Director of the Manville Corporation and Dr. Cartier the Quebec Asbestos Mining Association approached industrial Hygiene Foundation to determine whether it would be feasible to conduct an epidemiological study in order to discover whether the incidence of lung cancer was in fact greater among asbestos miners than among the general population and whether there was a correlation between lung cancer and the disease asbestosis The Foundation submitted in March 1956 pro- posal for such a study based upon a preliminary survey ofof t th he e type type and and and accessibility of data which might be available This proposal was accepted by the Association through its Secretary Mr. W. H. Soutar its General Counsel Mr. Ivan Sabourin Esq II 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 application of epidemiological techniques to their content and most of the authors do not make claim to having done so What has happened is that succeeding authors have drawn conclusions and generalized beyond the scope of the works which they quote Nowhere for ex- we ample have 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 63 Doll none of those reviewed gave any data on exposure paper by and dust concentrations and even Doll's paper merely mentions scheduled areas by which is meant those areas where processes are carried on which were scheduled under the Asbestos Industry Regulations of 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 . asbestosis as used may refer to changes observable only by microscopic examination of the lung tissue or it may mean a radiologically detectable condition Most of the published reports obviously included women them among their cases but some of 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 Hueper Hueper 122 in 1955 only ten appear to have originated in in the United United earlier States and seven in Canada Some of the 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 are also also also 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 few of which were referred to briefly in the previous section 7 7 . One of the most detailed studies and one which deserves the most serious consideration is 63 that reported by Doll in 1955 This study reviews causes of death among asbestos workers based on coroners It also attempts to estimate the risk by study- ing records of men who worked for at least 20 years in exposed situa- tions Doll concluded that lung cancer was a specific industrial hazard workers of certain asbestos and that after 20 years of exposure the risk is ten times as great as for the general population This article is important for several reasons in addition to the definite conclusions at which it arrives For example it begins by stating that in view of the infrequency of asbestosis this large num- 7 te . ber of cases 61 cases of lung cancer suggests but does not provepr-ove- that lung cancer is an occupational hazard of asbestos workers Neither this article or any previous one which we have examined presents any figures to prove that asbestosis is an infrequent occurrence Es- timates of the number of persons potentially exposed to asbestos dust in the United States alone vary from 10,000 to 35,000 and the incidence of asbestosis of any degree might be hhighier gher higher higher than Doll imagines This study like so many others involves autopsy records The number of persons involved in the statistical analysis is only 113 representing only 1,042 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 - also seems thatthis review does not add any new cases to the literature although Hueper in enumerating.9enume9rating.9 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 statement which it contains to the effect that the strongest strongest evidence that it lung cancer may be a hazard in asbestos workers has been produced by Merewether and by Gloyne An examination of these references leaves at least some question as to the strength of the evi- ) dence produced 92 In 1951 Gloyme presented a review of 1205 autopsies on persons who had worked in various dusty occupations Tais num- ber included 132 asbestos workers of whom 121 showed pneumoconiosig presumably asbestosis Primary 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 of these also showed primary cancer of the lung The incidence of lung cancer in other forms of pneumoconiosis was 6.75 and in 169 cases which proved not to have any type of pneumoconiosis was 8.3 Gloyne considered the mortality of the asbestos workers to be disturbing First First First of all it is obvious that the paper does not deal with the mortality of asbestos workers and secondly it must be borne in mind that all of Dr. Gloyne's cases were submitted him 9 for study because the 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 Dr. Gloyne's attention As a matter of fact in the same paragraph in which he expresses concern over the incidence rate in asbestosis Dr. Gloyne himself points out that the rate for lung cancer based on necropsies at the London Chest Hospital was 21.3 while the figures of the Registrar showed only 2.4 He thus recognized that autopsies on a certain selected group of cases were not representative of the general population It would seem then that notwithstanding the value of Dr. Gloyne'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 group of 121 cases selected for special study primarily because they seemed abnormal by preliminarypreliminary examination 17 or 14.1 had lung cancer lung spector of Factories reviewed all cases reported between 1924 1946 in which asbestosis 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 344 deaths including ~ 205 males and females 165 Among them were 55 55 cases 165 ) of of cancer cancer cancer cancer of 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 10 whose death certificate it was not mentioned may have been missed The import of this 16 is enhanced by the simultaneous statement that the incidence of lung cancer in autopsies of the general population is only % The danger of attempting to compare a rate found in 344 cases with the rate for the general population without respect to age occupation and many other variables such as smoking smoking habits is obvious Lynch 142 142 139 who with Smith had reported the first a - case in 1935 reported four cases of carcinoma of the lung in series of 49 autopsies on workers in an asbestos manufacturing plant who demonstrable were shown to have deposits of asbestos in the lungs This of course is not necessarily identical with the disease asbes- tosis Lynch himself points out that although this is an incidence of 8.2 both figures are too small for very serious statistical types of calculation Nevertheless later writers have used this paper to strengthen the case for an association of carcinoma of the lung with asbestosis is of interest to note that Klotz found only four in- stances of lung cancer in 473 cases of asbestosis a series 11 umes as large Behrens as quoted in Merewether , estimated that of 309 cases of asbestosis in the literature 44 showed associated cancer of the giving an incidence of 14.2 This is another case of generalizing an incidence obtained in a group of cases which were (~ undoubtedly reported only because some of them showed lung cancer to possibly hundreds of asbestotics whose cases were never reported The same applies applies to the conclusion of ( 192 ) 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 Werber Werber 205 who made the unequivocal statement that lung cancer would result in from % to 17 of cases of asbestosis allowed himself considerable latitude by qualifying it as regards time to an interval of 1 1/2 to 20 years 20 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 Nontube culous Diseases Diseases of the Chest 76 where the authors say simply simply an ex- cessive incidence of pulmonary cancer has occurred among workers in occupations other occupations such asbestos industries nickel copper ccopper opper refineries , stokers in generator plants etc. without substantiating substantiating substantiating substantiating substantiating substantiating reference reference reference reference reference reference reference reference reference . As an illustration of the ease with which a few reports which merely suggest a certain conclusion can through the lack of sufficiently critical attitude be summarized to produce the conclusion in a definite form 69 an 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 between asbestosis and cancer of the lung as settled As a final convincing argument it refers to recent experimental 12 12 observations by Nordmann and Sorge 161 . 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 investigator . Ewe Perhaps no one has written so extensively or so dogmati- 109-124 subject cally on the subject as has HHuepeur eper . 1955 1955 be reviewed the reviewed the cases 122 prior reported prior to that that date and enumerated a total of9999 by 63 Eleven these were those didiscussed scussed Doll and appear to hh ave ave . been cases covered by other authors Eight were discovered by Kenna- Kennaway 131 analysis way and in an analysis certificates and of death certificates and unless Merewether's study was incomplete these cases should have been in- cluded in his report Of the remaining 80 it is quite possible that tthhee the Gloyne 31 contributed by Merewether and the 17 by contain some dupli- dupdulpili-- duplidupli- cation with each other or with other 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 cancer since since some some some no exposure and therefore do not develop asbestosial 13 PRINCIPLES OF THE EPIDEMIOLOGICAL METHOD As has been indicated much of what is now thought to be pertinent concerning the comparative frequency of lung cancer in different population groups has 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 mass phenomenon It seeks to discover what propor tion of persons in a given set of circumstances will eventually develop the disease Epidemiology cannot predict whether a given individual will fall victim to a specific disease but predict aproxi- it can predict predict the the the approxi- approxi- approxi- approxi- approxi- approxi- ap roxi- approxi- mate mate mate number number number number of of cases cases cases cases cases of of this this this this disease disease disease disease disease disease which which which will will will will develop develop develop develop develop develop develop in a population population population population population population population population population 14 proceeds by first carefully and accurately describing describing character istics of the disease in different population groups and its essential objective is the formulation formulation testing and verification of generalizations concerning the disease in question In order to apply this method of investigation to the pro- 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 including the healthy as well as the ill 3. A sample which is truly representative ofthe population 4. Reliable and valid observations relating to the problem of the study A serious defect common to most of the studies which have been reported is that little or no information concerning the healthy people in the group seems to have been availablaevailable to the author Therefore results of these studies cannot properly be generalized to include such people In order to draw a generalization regarding all asbestos workersis necessary for study to include living persons as well as the dead Limiting the investigation to autopsied cases as has been frequently done in earlier studies still further restricts its use 15 in generalization The problem with which the Quebec Asbestos Mining Association is concerned is whether asbestos miners ex- perience more lung cancer than does the general population The answer necessitates the collection of reliable information on asbestos miners as a group as well as on the general population It seems advisable to discuss the differences between the epidemiological approach and that used in the studies which have been reported to date A very important consideration is the fact that lung cancer in spite of its increasing numbers is still a disease of low incidence that is in given population not many persons will contract this particular disease This fact requires that large samples or groups must be studied to provide meaningful results the Recognizing difficulty of obtaining such large samples most earlier writers deviated from the epidemiological method and sought to circumvent the requirement of observing well persons by 1. Comparing the relative frequency of cancer in various sites 2. 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 16 in the incidence of cancer of other sites This could be true even though the incidence 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 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 organs of cancer in other 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 larger group and that in dealing with such samples the observer may easily find more cases of any kind than would be found in group of of the the the same size but representative of the general population 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 tions is necessarily restricted It is the obligation of both the investi- gator and of those who read his report to make proper comparisons and to draw only those conclusions which are valid and justified A good statistical study of cases of cancer of the lung occurring in group of autopsies can lead to a proper inference concerning the frequency of lung cancer among cases coming to autopsy but only to such cases For information from such a study to be projected to some larger group it is necessary that the autopsies represent a good sample of that larger group To assume that such is the case in any particular series is dangerous and likely to be false There is some danger that the figures reported by some authors may be misconstrued as applying to asbestos workers or even asbestos miners when in fact the authors in question do not make this 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 investiga- tion The present study in contrast to the earlier works has been epidemiological planned to utilize the metho~ A 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 all members of this group have been collected and analyzed 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 13 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 healtheahlth 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 resp respectect to both the persons employed in the asbestos mining industry and mortality figures for the general population Following this exploratory survey the initial effort directed to the collection of data relating to all workers who had been processed through the clinic at Thetford Mines since its in inception 1947. Similar information was obtained regarding Canadian 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 19 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 Asbestos covering employees who had retired died or become disabled provided data sufficiently alike for the purpose of the study From this information it was possible to formulate for both Asbestos and Thetford Mines cohorts which could be well defined should be representative of each group and could be followed for 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 Thetford Mines in 1950 ? These cohorts were then followed by means of the annual physical ex- amination records through a year interval 1950 through 1955. All data regarding these groups were then tabulated in order to determine the characteristics of the cohorts For those who survived the entire period reference was made to the physical examination results and x- ray 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 had been tabulated They represent men who had left - 20 20 employment through retirement or resignation Eventually all but small number a of these were accounted for as either living or dead and in the latter event the cause of death was substantiated in deaths similar manner and the results added to the original list of 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 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 cc- death cupation date of hospital in which death occurred and whether or not an autopsy was performed Cases in which lung cancer was death but given as a cause of 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 all types types types types , and deaths from lung cancer These These were collected and and and and and tabulated tabulated tatbabulateud lated tabtabuullatead ted tabulated tabulated tabulated tabulated tabulated by counties and by sex for the years 1950 to 1955 inclusive From them death rates for the general population of Quebec and of individual counties were calculated for specific years and analyzed by cause Practically all employees of the Canadian Manville Company are covered by a group policy of life insurance which fortunately nearly all of them continue to carry when they retire A very few are not covered by this policy and those who leave the industry for one but reason or another except retirement this is likewise a small number As usually are no longer covered > . an additional check upon the information obtained from the clinical records on the group at Asbestos the records of the life insurance company were examined for all death claims paid under the policy and particular notice was taken of the claims in which the proof of death was based on cancer of the lung Deaths from lung cancer among asbestos workers were thus determined from the clinical records 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 proved , were carefully analyzed to determine possible relationship or correlations between the development lung cancer and any factor known from the 22 22 clinical records such as family history of cancer personal history history history of heavy smoking coexistence of asbestosis or exposure to asbestos In addition to this analysis of deaths occurring in the cohorts and during the years under observation every known death from cancer of the lung as well as every case diagnosed but still living has and been tabulated analyzed They will be discussed separately from those included in the population and interval under study A comparison of lung cancer mortality in the asbestos pro- ducing cou: nties has been made with that in counties which are far re- moved from the asbestos mines and in which presumably no asbestos miners 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 most recent recent pub- pub- lished and unpublished material In order that tthehe methodmethod by by which these comparisons have been made may be more easily understood it seems advisable to discuss 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 one in ten ! However should a sample of ten marbles be down from the container it would not be unlikely that 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 tabulation shows a calculation of the probability that a given number of black marbles will be found in sample of ten No. of Black Marbles in Sample - 0 3 78 10 10 Total Total Total Total Total Probability . 3486784401 .3874204890 .3874204890 . 1937102445 . 0573956280 0111602610 .0014880348 .0014880348 .0001377810 .0001377810 . 0000087480 . 0000003645 0600000000 0000000001 1. 0000000000 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 oo would be anticipated that the sample would contain four or more black C 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. In practical applications of sam- pling the percentage of black marbles is of course unknown and 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 witha known probability that the true value lies within a certain range If 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 distribution which has just been described This is a substitution frequently made under these conditions because the Poisson distribution is tabulated and the differences between it and the binomial distribution are quite smail It is based on the equation Where e = 2.71823 the base of natural number of man years subject p = incidence rate logarithms to risk x = number of cases observed The logic of the statistical approach may also justify a few words of clarification Generally in problems of this kind one sets up a hypothesis which in our case would be Asbestos miners not 25 25 . higher have a rate of mortality from lung cancer than the general popu- lation The hypothesis is then tested by means of the study of data en asbestos miners and on the general population including the observed number of cases of lung cancer From what has been said earlier it is clear that even if the asbestos miners and general population had ex- actly the same lung cancer mortality rate it is unlikley that in any single sample this identical rate would be found Some difference is likely to be observed but the important question is whether this differ- ence is greater than might be expected merely as a matter of chance In other words we wish to know whether the difference is statistically sample should significant If 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 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 % of the time by chance there is sufficient evidence to reject the original hypothesis If on the other hand the value observed even though larger than the expected value is no greater than might occur by chance in fewer than % of trials we have insufficient evidence to reject the original hypothesis Calculations and conclusions based on the results of the find- ings in this study have been made in conformity with these statistical concepts They will be presented in the following section 26 26 V. RESULTS AND INTERPRETATION The two cohorts which were constructed according to the criteria described in the preceding section section have been considered individually 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 Original Cohort Lost Persons Deducted Final Cohort Living in 1955 working and retired Dead by 1955 Ca. of lung Questionable Ca Other Causes Unknown Causes of lung Smokers Nonsmokers Unknown Asbestos Cohort 2327 54 2273 2224 49 3 0 46 0 1931 340 2 Thetford Mines Cobort 3764 79 3685 3547 Summary of Combined Cohorts 6091 133 5958 5771 133 ^ 3 123 6 2742 925 18 137 3 169 6 4673 1265 20 E E - 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 had worked longer as asbestos miners 19 years as against 15 years A comparison of the exposure to asbestos dust is presented in Table 3. All workers were placeidn 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 for each job category was determined after consultation with persons familiar with the environment and conditions in 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 II while the Asbestos group occupy mainly the extremes of exposure For For For For the purposes of calculation the assumption assumption has been made that the relationship between these categories is linear and that category II is twice as dusty and category III three times as dusty as category I. | The fourth variable smoking habits smoking habits was similarly tabulated and is shown in Table 4. A larger percentage of smokers is indicated indicated here for the Asbestos cohort - 85.0 compared with 74.4 23 23 Number and Percentage Distribution of Asbestos and Thetford Mines Cohorts by Age . . Asbestos Age queueibeeges No. % 20-44 45-54 55-64 65 + Unknown Totals Av Age 1602 447 185 39 2273 39 * Less than .5 70 20 8 2 100 , Mines No. 2299 677 430 276 lis 62 18 IZ 8 3635 42 100 Combined No. 3901 66 1124 19 615 10 315 5 5958 41 100 . ( TABLE Z Number and Percentage Distribution of Asbestos and Thetford Mines Cohorts by Length of Employment Length of Employ- ment Asbestos No. fo 5-9 880 10-19 864 20-29 342 30-39 168 40-49 17 50+ 50+ 2 Totals Av Yrs 2273 of 15 Employment 39 39 15 7 I = 100 * Less than .5 Thetford Mines No. 915 1534 580 435 168 53 3635 19 25 42 16 12 + ) 100 Combined No. 1795 2398 922 603 185 55 5958 18 30 ' 40 16 10 3 : = 100 - C : 7 TABLE 3 Number and Percentage Distribution of Asbestos and Thetford Mines Cohorts by Exposure Category . > Exposure Category Asbestos No. % I II III Unknown Totals Av Exposure 969 564 735 5 2273 1.9 _ * Less than .5 43 25 32 1807 1807 Thetford Mines No. % 1062 1586 1037 0 3885 2.0 29 43 28 0 100 Combined No. % 2031 2150 1772 5 5958 2.0 34 36 30 = 100 ' TABLE 4 Number and Percentage Distribution of Asbestos and Thetford Mines Cohorts by Smoking Habits Smoking Habits Asbestos No. *5 Smokers Nonsmokers Unknown Totals 1931 340 2 2273 _ = Less than .5 35 15 = 100 Thetford Mines No. 2, 2742 925 13 3635 74 25 l 100 Combined No. *, 4673 1265 20 5953 ? 21 2 100 30 30 This is a difference which could hardly occur by chance because of the large 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 ofemploymvearniets at the two locations locations In spite of the minor differences brought out by these comparisons it would seem that the two cohorts are quite similar similar similar similar with regard to the variables of age length of employment degree of exposure and although less so in regard to smoking babits These variables appear to us to be those most closely related to the problem and will be taken into account in comparing the workers with the con- trol groups Table 5 presents the year 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 cze of primary cancer of the lung when the records showed that the diagnosis had been supported supported by an by autopsy autopsy autopsy or surgical resection surgical microscopic examination of the removed tissue In one case so sidered sidered sidered however diagnosis was confirmed by bronchoscopy with zation and biopsy In another although there was nosis of primary cancer of the lung seems to have 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 31 . : TABLE 5 - Part Study of the Asbestos Cohort No. Alive At Beginning Year of Year Cause of Proved Suspected Primary Primary Ca.of Ca. of Lung Death Other Causes "" Man- Unknown Years of Risk 1950 2273 1951 2267 1952 2261 1953 2252 . 1954 2243 2231 Totals 0 I 0 0 DON DON M 0 6 ............... 5 ............... 9 ............... 9 ............... 12 ............... 5 46 0 2270 0 2264 0 2256.5 00 2247.5 00 2237 2227.5 13502.5 Proved cancer of lung death rate per 100,000 years of risk = 2222.2 .2 3 13502 13502 TABLE 5 - II Part Study of the Thetford Mines Cohort No. Alive Beginning Year of Year Cause ai Proved Suspected Primary Primary Ca. of Lung Ca. of Lung Death Other Causes Unknown ManYears of Risk 1950 3685 1951 3675 1952 3661 1953 3633 1954 3605 1955 3579 Totals 1 2 ^ 1 3680 I 0 12 1 3663 8) 0 23 0 3647 22 1 25 0 3619 oolm 123 21769 22 oolm 21 . 3592 l oolm 31 0.10 3563 ^' 0.10 Proved cancer of lung death rate per 100,000 100,000 years of risk = 27.6 27.6 ^ Suspected plus proved cancer of lung death rate per 100,000 man years of risk = 41.3 21769 21769 : TABLE 5 - Part III : Study of Combined Coborts Combined death rates per 100,000 years of risk for Asbestos and Thetford Mines Proved cancer of lung death 100p,er01000,0000 100,000 years of risk risk = a 25.5 3355227711..55 35271.5 Suspected plus proved cancer of lung death rate per 100,000 man- years of risk = 34.0 3527112 .5 e 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 autopsy but there was a difference of opinion between two pathologists as to whether lung cancer was present The term years of risk has been used to mean the number ofmmenen at riskffor or the year under observation An individual who lived throughout the year was counted as a full year of risk but one who died during the year was counted as onehalf man year Deaths occurring in these two cohorts and in which lung i 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 ASBESTOS COHORT e Lung Proved Cases of Primary Primary Primary Primary Primary Cancer of the Name Age Smoker Exposure Died Au- topsy Asbestosis 1. A. J. 66 Yes 26 Yrs Cat H 10-12-51 . 1. N. P. 65 Yes Yes Yes 34 Yrs in Cat I 5- 3-55 Yes No 3. M. 65 Yes 37 Yrs in Cat I 7-20-55 No No C . ; THETFORD MINES COHORT Proved Cases of Primary Cancer of the Lung * Name Age Smoker Exposure Died "Asbes---- -- -- t--osis 1. --. -- . 59 2. A. S. 48 3 W. 61 D. 56 5 E. L. 37 6. A. R. 68 Yes Yes Yes Yes Yes Yes 32 Yrs in Cat 22 Yrs Cat 33 Yrs in Cat 30 Yes 16 Yrs in Cat in Ca 28 Yrs Cat I 8-20-50 51 UI 4-30-53 II 11-22-53 I 8-3-54 8-3-54 TET 5- -55 ves Yes Yes Yes Yes Bronch No Yes Yes Yes No No Suspected Primary Cancer of the Lung Name Age Smoker Exposure Died 1. J. T. 2. D. 3 P. Yes 46 Yes 65 Yes 32 Yes 33 Yes 42 Y in Cat in Cat Cat fF 10-25-50 III T- -53 II 9-30-55 Au- tsosv Asbestosis No Yes No No Yes No 24 24 " At Asbestos there were no cases in which the diagnosis was questionable with the result that the rate for proved cases in cohort this is the only one developed At Thetford Mines however the three cases mentioned earlier were placed in the category of suspected primary cancer of the lung lung An indication of the impor- tance of these cases ininterpreting 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 for 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 Thetford Mines group As was explained in the section on Coi- lection and Analysis of Data it would then not be unlikely for six cases to occur in our sample This is in fact the number number number of of fouinn d the Thetford Mines cohorctohort E E however the the three suspected cases are included increasing this whole situation changes from a statistical point level of probability in this case falls between 9 the hypothesis that there isno difference between the incidence cancer in miners andthat in the general population if we found 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 nine nine cases cases cases cases cases in in this this this this sample sample would show a 35 35 . an increase in rate which approaches the significant level Because of the tremendous importance of the questionable cases in this respect some detail regarding them will be given here In one of these cases the suspicion of cancer of the lung is based upon the 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 ray appearance of fibrosis es- pecially if a localized density or a superimposed tuberculous lesion is tumor present can simulate that of a 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 mortem examination In the third case although it was subjected to autopsy two pathologists disagreed as to whether lung cancer cancer was pre- pprre-e- 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 cannot in fairness be disregarded completely On the other hand they It is for this reason that mortality rates for the Thetford Mines cohort and the combined co- hort have been calculated both ways different Table 6 giving the rates by age groups reveals experiences for the two cohorts It happens that all of the deaths deaths in in the C . ( ( : Asbestos cohort fall into one age group so that the rate for that age category is exceptionally high At Thetford Mines a more even distribution 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 TABLE 6 year Number of Persons and Number of Lung Cancer Deaths by Age Groups Asbestos Thetford Mines Combined Lung Lung Cancer Lung Cancer ; Age Cancer Deaths Deaths Groups Persons Deaths Persons Proved Total Persons Proved Total 20-44 1602 Q 45-54 447 0 55-64 185 0 65+ 39 wlow Unknown 0 wlow Total 2273 wlow 2299 1 ,, 3901 1 NIM 677 I 3 1124 i NIM 430 3 3 615 W 3 276 4010 2010 315 % 10 3 4010 2010 3 010 10/21 3685 4010 2010 5953 010 10/21 Annual Lung Cancer Death Rates per 100,000 100,000 Years of Exposure by Age Groups Age Group Asbestos Total 20-11 45-54 55-64 75+ Unknown Over No one exposed 0 0 Q 1292 * 22 Thetford Mines Proved Total ; 25 116 60 0 27 1 74 116 121 0 41 Combined Proved Total + 15 31 212 0 2.5 + 44 3 _ 265 0 34 - The rates by length of employment Table 7 show that the two groups were quite similar in this respect During the 40 years of employment the rate rises an observation which first 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 years of exposure When the suspected cases are added one case does show up in this period This would produce a rate of 69 per 100,000 100,000 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 asbestos long exposure and if is a carcinogenic agent it must be con- cluded that these 240 men have demonstrated considerable resistance phenomenon This is biological which has been observed previously and is consistent with the theory of an intrinsic or endogenous factor in can- cer The only other explanation would be that the susceptible members of this age group had died earlier of lung cancer Table 22 which ap- pears later in this section indicates that the members of the cohorts did not die from lung cancer at 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 cobort the rates actually de- crease with increasing degree of exposure and at Thetford Mines they appear completely independent of exposure if we count only the proved cases . 33 TABLE 7 Number of Persons and Number of Lung Cancer Deaths by Length of Employment Length Asbestos Thetford Mines of Lung Lung Cancer Employ- Cancer Deaths ment Persons Deaths Persons Proved Total Combined Persons Lung Cancer Deaths Proved Total 5-9 10-19 20-29 30-39 40-49 50+ Total 880 864 342 |. 168 17 2 2273 915 1534 1 580 2 435 00m 168 00m 53 3 3685 0 23010 0 1795 0 0 23010 1 2398 I 0 23010 2 922 m 0 23010 5 603 in 0 230010 I 195 0 0 23010 0 55 0 0 230010 3 5958 0 t 3 7 1 0 / Annual Lung Cancer Death Rates per 100,000 Years of Exposure by Length of Employment Length of Employment 5-9 10-19 20-29 30-39 40-49 50+ Over ' Asbestos Total 0 0 49 198 22 Thetford Mines Proved Totzi 0 11 57 115 0 27 0 11 57 192 CC Combined Proved Total 0 7 54 138 0 G 33 0 7 5+ 193 90 0 3 39 TABLE 8 Number of Persons and Number of Lung Cancer Deaths by Exposure Category Expos- Ure Category Asbestos Thetford Mines Persons Cancer Deaths Persons Lung Cancer Deaths Proved Total Combined Persons Lung Cance Deaths Proved Total I 969 II 564 . III Unknown Total 735 5 2273 0m 1062 1586 1037 0 3685 201 Nmtola 2031 + 4 Nmtola 2150 Mnolo + 1772 Mnolo 4 Nmtola 5 5958 Mnolo 0 Mnolo IZ Annual Lung Cancer Death Rates per 100,000 Years of Exposure by Exposure Category Exposure Category I II Unknown Over Asbestos Total 34 30 0 0 22 * No one exposed Thetford Mines Proved Total 31 Howw 21 Howw 32 Howw Howw 27 Howw Proved Total 33 33 23 31 19 37 0/100 0 0/100 34 If 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 found interpreta- The only possible error in this tion could occur if the weighted exposures were inversely related to of years employment in which case the heaviest weighted exposure category III would show the shortest length of employment Tables 10 and which list the number of persons in various exposure categories by length of employment indicate that this error has not occurred In fact the average number of years of employment for each exposure category is almost identical TABLE 9 Number of Persons in Various Weighted Exposure Categories by Length of Employment Asbestos Length of Employment 5-9 10-19 20-29 30-39 40-49 50 + Total Av Yrs of Exposure Weighted Exposure Categories 11 g aa 423 273 159 98 g 2 969 15.5 213 217 89 42 3 0 564 15.2 239 373 92 27 < ) 735 14.5 Unknown Total 0 ! 2 1 1 29.0 330 364 342 163 17 2 2273 15.1 ( - C ; TABLE 10 - - 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+ 50+ Total . Av Yrs of Exposure Weighted Exposure Categories i ,, LII Unknown 279 390 155 149 67 22 1062 19.9 7 385 666 274 176 64 21 1586 18.7 251 . | 478 151 110 37 10 1037 13. OF Q 8) 0 0 0/0 0/0 Total 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 Employment 5-9 10-19 20-29 30-39 40-49 50 + . Total Av Yrs of Exposure Weighted Exposure Categories H It fo 707 663 314 247 75 24 2031 17.8 598 333 363 219 67 21 2150 17.8 490 351 243 137 41 10 1772 16.6 Unknown 0 i 2 I 1 0 5 29.0 Total 1795 2393 922 603 135 55 5953 17.5 a Table 12 which develops the rates for smokers and non- smokers is most striking It shows that not single case of lung cancer developed among the 1265 nonsmokers and that all cases of lung cancer both proved and suspected occurred in smokers comparison A of Tables 8 and 12 certainly suggests that smoking is a greater bazard than exposure to asbestos in the mining operations Table 12 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. e.g. the nonsmokers may have included a larger percentage of young men Consequently additional Tables 13 14 and 15 were constructed to show the distribution of smokers and nonsmokers by age length of employment and degree of exposure Although there are slight differences they do not account for the fact that all observed cases of lung cancer were in smokers In respect to age Table 13 the combined average age of the smokers was 4.9 years less than that of the nonsmokers Table 14 shows that as far as length of employment is concerned the smokers had worked about 2. years less on the average than the nonsmokers With longer exposure and greater age one would expect the nonsmoking group group group group to to show show show show a higher higher higher higher higher higher rate if lung cancer were due to asbestos Table 15 shows that the average exposure category was almost the same for the two groups Therefore this variable seems to be of no importance in accounting for the difference between lung cancer death rates for smokers and nonsmokers . . TABLE 12 Number of Persons and Number of Lung Cancer Deaths by Smoking Habits Asbestos Thetford Mines Persons Lung Cancer Deaths Persons Lung Cancer Deaths Proved Total Combined Persons Lung Cance Deaths Proved Total Smokers 1931 3 Nonsmokers 340 0 Unknown Total 2 wlo 2273 wlo 2742 60010 925 60010 18 60010 3685 60010 9 4673 0 1265 olo 20 olo 5958 000la IZ 000la 000la 9 Annual Lung Cancer Death Rates per 100,000 Years of Exposure by Smoking Habits Smokers Nonsmokers Unknown Over Asbestos Total 2001 2001 2001 22 Thetford Mines Proved Total 36 0 35 0 0 ol t Combined Proved Total 32 43 0 1/000 0 1/000 26 26 1/000 -"f' _ -un uMOoUy 21 b z 1 { ve L OF _ Number of Smokers Number 0 Smokers Smokers and Nonsmokers Nonsmokers Of @ ednoarn Asbetos o07 968 {1b rT Thetford Thetford Smoker 1361 371et Unkown 38.5 Percntage Percentage 2.10 known 449 Binoker Smoker 1 rd I I 248 180 2 3 saxOUTE 0 Gh o8l 128 S26 147 Z 46.4 41.0 41.0S7Zsghz 39.8 ZHLZ 46.4 Distribution Distrbution I ! of Smokers Smokers Smokers and AUN Asbetos Asbestos Asbetos Orz Si. 22 C 0 Thetford OL Thetford = known 0 50.0 1L <91 9% 1e6t 48.5 RdNo .9 aryPh-07 0 b9-S 4.7 9.0 (rae, 19.5 15.9 NnUMOUT 0 09 002 a'o! 0's 0 S 001 Age Groupa uoNdayoulA SES Lut o9I Bll O wv0t o8y Aq Combined Combined Combined n se %W00wl know Smoker Bmoker Bmoker known 12 known 9 Soor 896 S 1 tlonNdayoutA "Rti9ot$61 691 0 %on1 40.7 164 129) 40.7 40.7 a ANTT 4 .2 JO Age Groups Groups Q 0 0S rh 0 AOL Nonsmker ROPRIAY Un- -OK Combined Combined Combined s*9 6 0Kol amoker known CY amoker 5.1.5 Zl 60.0 60.0 0 mood AGO" Ta 3.51.8 1.8 'S-SF 5.0 5.0 UAOID,UA Pae, Pe 45, nNuMoUy ot b Zz r 0 0 Ik O 9T paid 2) UMOUY 0 0S 0 07 0 O! 0 02 0 0 20 t Number Smoker 720 296 vi Length 15.4 Pue Percntage Jo raquiny fo of ~UON Smokera LLe 92F TABLE TABLE TABLE zz 14 < 6r TD Asbestos Bort L961 @2L teh Ol Ct Thetford O Lt , umokerumoker smoker known known Smoker Smoker Smoker Smoker 159 16 218 29/0 0 1-16 0 S3 @z 126 126 285 1-16 U6 ProyU ATIYO gag 2 97h 2742 2742 le 21.3 925 UIC UmMOoty I t 0 0 0 0 z -un O'll = Distrbuion Distrbuion and Distribution of Smokers Smokers Smokers Nonsmokers Nonsmokers Nonsmokers Y Asbetos known Un- known Sinoker 91 z smoker Non- Ia Employent Employent ~UON OWIR062Lee 2S1ret 6Sa1 Zoot yo Combined I'2k "SI < b6*2 L* %20 t wusy Combined Aq smoker 37 smoker known known known 0 0 %001 HIDPOWBUA] RAWIE ~uoN 199 L te i est 0 8 rez Zo t PAOJIUL 19 Pte .1265 16.0 20 Ot ae 9 rt 20 1 .1265 AAO UMOtH, TOWIS aura | 00s 0 0S 0 0 O 0 =%0 l Jo = Length Length Employent NON EmploymentEmployment Employment Get 67S <0= %*OT Combined % known umoker umoker RHE known Un- R I" 001 13.5 16.5 33.5 16.7 13.5 3.7 JU G-S GI-Ol 0 15.6 10.1 10.1 105 (P97, 15.8 VUE 8.0 Jo 15.4 -Aaqdurey 15.7 13.1 13.1 61-01 20.0 20.0 6b -Or 10S POE ou oe] . ~ UMOLD t i 6 0 02 < 2 1 paujqiey -Uon 4ayOUIE Lb eS BEC 1515 Number Smokers and Nonsmokers Nonsmokers Nonsmokers Nonsmokers Nonsmokers Nonsmokers AsbetosAq known 483 -un Un- E 9 6 Non- Thetford Thetford smoker smoker 0 uoN QTE 1208 1208 S26 372 1931 erayowsu Psa, 1.5; =e. 2742 2742 0 zeiz 925 pur ~tyy UMOIDp 1 I 0 rt)2 S t Distrbuion of Nonsmokers and Distribution Smokers Smokers and Nonsmokers Distrbution Smokers Thetford Asbetos Un- orn CH Thetford Thetford Non- atnokerthan i 28.9 28.9 50.050.0 25.6teIO25.6 trg 25.6 0 unWMO 0 02 O'SE "SP 0 ZOOL Ad Asofpury poaurqioy UuoNJOUTe GLE "LSEL9210 6008 Category Category axyoUtG ce z9E SOE 10 oor Afq Combined Combined Combined EE Un- O oor Smoker 474Smoker Q Pr]8z UON ZEZOF 7 oot Gayotre 1265 Pur aT, 1 O'rP 20 0 oor po InWMOUY 0s OOS ohoor Category Category Exposure CategoryCategory CategoryCategory Gti L6?t.w%or e 7 ee Combined Combined 0G? Un- soor Smoker e I 35.0 35.0 SPANCUED Made 26.7 35.7 .0 e The result of this additional analysis is that 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 87 one study as high as 133 135 147 154 195 However data on cases of asbestosis from the cohorts at Thetford Mines and Asbestos pro- duce a rate of only about % is true that these data are based on only those cases which have been proved at autopsy and those whose most re- cent 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 of 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 rate of less than 10 which is far below those widely reported In our combined cohort there are 1765 men who have had more than 20 years of employment and 431 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 very considerable reporting of asbestosis Such a hypothe- sis is easily conceivable when one considers that many chest rays in this group may be considered normal by comparison with others in the same group whereas if they were to compared with what are considered as normal chest 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 13 1/21 1/21 Thetford 36 30 116 Combined 104 34 133 49 TABLE 17 - Part - 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+ 50+ Total Av Yrs of Employment Exposure . Category I II HI OONOOO 0 0 OONOOO l 2 OONOOO 7 4 OONOOO 1 4 OONOOO 0 1 0/0 OONOOO 0 NN 0/0 11 25 25 - 29 Unknown Total 0 0 0 3 0 13 0 5 0 I 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+ 50+ Over Exposure Category I H tt 0 0 1.3 0 0 0 .5 7.9 2.4 #ON #ON 1.6 0 .5 4. 14. 25.0 " 1.5 * No one exposed in this group Unknown = O 0 O O 10 10 Total 0 .3 3.8 3.0 5.9 0 1.0 60 C . TABLE 17 - Part II -. Number of Asbestosis Cases By Category Length of Employment and Exposure Category Thetford Mines Length of Employment Less than 10 10-19 . 20-29 30-39 40-49 50+ 50+ Total . Av Yrs of Employment Exposure Category I II III CONNOO CONNOO CONNOO CONNOO CONNOO CONNOO + 30 . --,---- --,---- --,---- 15 6 2 29 36 0 7 21 33 20 2 83 34 Unknown 0 0 4) 000/0 000/0 000/0 000/0 Total 0 8 28 50 26 4 116 34 ( Percentages of Asbestosis Cases By Length of Employment and Exposure Category Length of Employment Exposure Category I a it Less than 10 10-19 20-29 30-39 40-49 50+ 50+ Over 0 0 1.3 1.3 0 0 4 0 Z 1.8 8.5 9.4 9.5 1.3 * No one exposed in this group 0 1.5 13.9 30.0 54.1 20.0 3.0 Unknown Total 0 O 5 O 4.8 O !! O 15.5 an 7.5 0 3.1 TABLE 17 - Part Number of Asbestosis Cases By Length of Employment and Exposure Category Asbestos and Thetford Mines Combined Length of Employment Less than 10 10-19 20-29 30-39 40-49 50 + Total Av Yrs of Employment Exposure Category I 7 III 0 0 4 2 0 0 6 28 ON ON 12 16 6 2 ww ww 0 9 25 37 21 2 94 33 Unknown 0 0 0 0 0 010 010 Total Q 11 +1 55 27 4 138 33 Percentages of Asbestosis Cases By Length of Employment and Exposure Category Length of Employment Exposure Category I i iu Less than 10 10-19 20-29 30-39 40-49 50 + Over 0 0 13 3 0 0 .3 0 .2 3.3 7.3 9.0 9.5 1.8 0 1.0 10.3 27.0 51.2 20.0 5.3 * No one exposed in this group Unknown -- 0 0 0 Q = 0 Total 0 .5 4.4 9.1 14.6 7.3 2.0 52 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 be noted that within an exposure category the incidence rises with increased length of employment is also apparent that the incidences even in the category of heaviest ex- posure are far below the rates found by the authors previously referred 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 all the other studies there has been a gross under- asbestosis reporting of the 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 TABLE 18 - Part ' Statistical Analysis of the Causes of Death Asbestos Cause Asbestosis No Asbestosis Total Lung Cancer ( .2 2 2.3 3 No Lung Cancer 3 3.8 43 42.2 46 Total + 45 49 Percentage 3.2 71.8 Figures in parenthesia are the expected numbers Percentage 6. 93.9 - TABLE 18 - Part II Statistical Analysis of the Causes of Death Thetford Mines ~ Cause Lung Cancer No Lung Cancer Total Percentage Asbestosig 3 1.3 25 26.7 28 21.2 No Asbestosis Total Percentage 3 4.7 101 99.3 104 78.8 6 126 132 4.5 95.5 Figures in parenthesis parenthesis are the expectedexpected expected numbers TABLE 18 - Part III Statistical Analysis of the Causes of Death Asbestos and Thetford Mines Combined Cause Lung Cancer No Lung Cancer Total Percentage Asbestosis 4 1.6 28 30.4 30.4 32 17.7 No Asbestosis 5 7.4 141.6 149 82.3 Total Percentage 9 172 131 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 chi- square test of significance The importance of the reporting of asbestosis can be observed in Table 19 54 54 - TABLE 19 . Statistical Analysis of the Causes of Death if 20 Nonasbestosis Cases had been Diagnosed as Asbestosis Cases Cause . Lung Cancer No Lung Cancer Total Percentage Asbestosis No Asbestosis 4 2.6 48 52 28.7 51 6.4 124 122.6 122.6 129 129 71.3 71.3 . Total Percentage 9 172 181 181 181 5.0 95.0 Figures in parenthesis are the expected numbers In this table it has been assumed that 20 of the cases which did not have lung cancer and which were reported to have no asbestosis did in fact have asbestosis the diagnosis of which was missed Although the cases of lung cancer with asbestosis are still higher than would be expected the difference is no longer significant the 95 level This still is true if fewer than 20 cases were shifted but it is reasonable to expect that at least 20 of the 144 might have shown asbestosis had they been subject to autopsy 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 reporting c^>as- bestosis has been stressed because it it seems so obvious that in under- reporting asbestosis the relationship between it and lung cancer has been made to appear more significant than it probably is 55 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 while this is slightly lower than the rates found by Merewether Gloyne and Wedler is still much higher than could be expected if the asbestosis incidence were anywhere near the experience reported by other authors Comparison of the Cohort Experience with that of the Province of Quebec Dominion of Canada and the United States In order to make a comparison of the experience among asbestos miners with that of the general population of the Province of Quebec statistics were gathered as stated earlier in the office of the Division of Demography in the Provincial Ministry of Health Health The The data on total deaths deaths from all forms of cancer and deaths from from from ffromrom cancer of the lung were obtained by sex and by county for the years 1950 through 1955. In addition all death certificates which specified primary cancer of the lung and all those which indicated lung cancer but did not specify the origin were examined for the years 1952 through 1955 a 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 these segments be.noted It will 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 number 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 For this reason the years 1954 and 1955 were thought to be more nearly representative of actual conditions Even so is quite likely that the general population is not studied for lung cancer with the same diligence with which this disease is looked looked for for for the in the the miners miners miners miners miners and and 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 cobort showed no such increase over the same period cancer rate of cases in which the death certificate merely merely merely merely merely merely read read read read cance cancecance cance cance : of the lung as distinguished from those in which the diagnosis was [enuy aod 000 ajey VOL 9 22 Uz? 1 22 O'IF L2 S 2e = IvI9OJ, FZON t < 6 9 2t9l Comparison PAOVIDUT, pur soyqey Of Cohort Proved doqQanvH Colort , SS6l fst Z Z 1 | and S6L C0 0 0 eyIetag of EOE 0 0 Persone 1,98,0 SZ 0 22 1,198,00 2,261 zz { -- 1 t ZOE Lung Cancer Cancer 303 245 0 . I 1 0 3,6 2 HE 0 0 1 < f6f DOUFAO 193 29C CY Jo 1,192,00 000 000 Excluding 1,192,00 1,192,00 BGT I 300 Workes WAOND RUDIYO ausined lung deaths A poulationTE population 1951 1951 ta deaths enumrated poulation for DemographicDemographic nm ~ RSGT narod 40) + Yor Oz jo minde UDI40} ale pareuyis HYUIeapP ony Total 10,0z9UeD 1624 Sung 40J ef ww3 op ager qpe ear yaody 41.0 27.3 paumear yy) 16 2Woaq 2 .5 apt wer Jo qe fanty jurod-pre yto up yearspoulation atitn ayy . ay 4 4 53 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 in 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 berween the specific rates shown in Table 21 and those for the cohort shown in Table 6 the Province An average of the 1954 and 1955 rates for 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 the average of the 1954 1954 and 1955 figures for the Province is true that in the case of the age group of 65 and over the five deaths provide a figure which which which is al- most significant at the 95 level However it should be noted that of this number includes one 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 that the exact cause of death in the very old is not a very m maa ttter mat tter er of the same intensity of interest as is in younger persons 59 Before leaving this comparison of the Province with tthh e e miners it should be shown that their age distributions are reasonably the same That thisthis is the case can be observed from the following tabulation Age Distribution of Adult Males for the Province of Quebec Rapport 1954 1951 Age Group 20-44 45-54 55-64 65 + Total Number 727,135 188,952 128,944 I13,467 1,158,498 Percentage 63 16 . 11 10 100 Percentage Combined Cohorts 66 19 10 5 100 It should be remembered that the miners retrierteire and con- sequently it can be expected that the oldest age group group will be larger in the general population The data presentedpresented in Table 23 indicates that the the lung cancer rate generally decreases after age 70 and we could expect the rate for all people over 65 would be smallersmaller than than the rate for a group of 65 to 75 which would would apply to the oldest miners It is felt that by using the whole adult male adult population we have developed rates which are are somewhat lower than if we had been able to exclude the general population over 75 . o * 6 PACLIY Teioy ze Ls bg zs . - P2pjroadg Aavwyag [eID it 95 9tt REILee out oF S 6] Bayuty Deaths Deaths Deaths for Death Province Cancer he Lung Certifcates jeloy Total 09. 1954 1954 ZhE Specified EstimatedPopulation Primary Total Proved 62 ze OZ 66 20,07,0 pasyjoadg Kavuiyag Primay IZ Total 137,00 AMV 1,237,00 1,237,0 1,237,0 poulation poulation 100 V1 38 69 ng tot 29tog] Arc applying applying ap lying 1951 1951 given percntages obtained percntages 1954 given Aq for [TIOF, Lt tg ool | S62 up Rates Tune; & Certifed Certifed uoepndo per Specifed 1954 1954 doo vou Lek 702Specified Specified eg , Certified Primary sor Proved peaed z"I Bist 7h 904Lil |partadsawaywie, 22Lol? en e712tle pakotg S561 a7 z I Cll UF 971S*tt 195Total T0o0t0al 107, SpecifiePdrimary Primary Specifedgee 29d 15 Aarts 60 paetg 116 rR rE2 570'8 148 age males MI the total totalRSI groups Tae PaAOF 10,0 Le | blz lard L*6 pean ET 1957 n (Ete, 27 76k EL L716, 07 vorepndaayreps 17.8 1 27.7 hE-02 21.3 50.1 99 23.1 4 TER 27.7 - 84.7 27.7 GS! 15.8 41.6 APA 61 TABLE 22 Comparison of the Actual and Expected Number of Lung Cancer Deaths by Age Among Asbestos Miners Age Group Province Specified Total Specified Primary Rate per 100,000 No. of Miners 20-44 45-54 55-64 65+ 65+ Unknown 1.8 24.5 67.6 89.3 -- 3901 1124 615 315 3 * Actually.4 Actually.4 Expected No. of Deaths Observed No. of Deaths Proved Total 0 2 2 2 -- I I 1 3 3 3 4 5 0 0 + The expected number is based on the average of the 1954 and 1955 specific rates for the Province of Quebec eee blew eb oe wanes ame oe. Cr a. es Table 22 also answers a question previously raised It shows that the members of these cohorts have not died from lung can- cer 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 of the Dominion as a whole was made using statistical material from several sources In one source Phillips 171 Phillips gave age- and sex- specific rates for Canada for three periods berween 1931 and 1952 The rates for males are given in Table 23 62 ( . C . . . TABLE 23 . Annual Death Rates per 100,000 for Cancer of the Lung in Canada Age Groups Under 30 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85 + All Ages 1931-1933 0.2 0.9 2.0 3.0 5. 8.2 IZ.7 12.5 15.1 10.7 15.8 8.2 11.4 2.8 Groups of Years ; 1941-1943 0.3 0.9 3.2 5.4 12.5 18.9 27.0 33.7 34.5 30.6 30.0 27.9 14.3 7.1 1950-1952 1.0 0.8 3.0 6.5 16.7 37.2 59.7 77.3 102.9 86.3 83.9 59.7 71.0 15.3 * Mortality from Lung Cancer in Canada 1931 to 1952 These figures show strikingly the increase in rates between 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 diagnosed in the older age groupgroupss in the general population To use these figures for purposes of comparison is necessary to combine the rates for certain age groups in order to conform to the age distributions used in this study Since the exact . populations in each age group for the years indicated is not known 63 63 . this must be an approximation However the rates would be somewhat as follows Age Group 20-44 45-54 55-64 65+ 65+ Rate . 5 27 69 90-95 These rates are in general lower than those developed for the total proved and suspected cases of lung cancer among the asbestos miners The only large difference however is in the age group of 65 years and over and it is quite possible that the rate for this group may 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 -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 1950-1952 1950-1952 rate and compares with 25.5 per 100,000 for proved cases and 34.0 per 100,000 100,000 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 the general population of Quebec and the Dominion of Canada ( - Since is probable that figures for the United States are more complete and therefore possibly more comparable comparable to the data for the miners specific rates were computed from Vital Statis- - tics of the United States Volumes I and II for 1952. These rates have been tabulated in Table 24 C Number of Deaths and Death Rates per 100,000 by Age Groups for the Adult Male Population of ' the United States From Vital Statistics of the United States Volumes I and II 1952 Age Group 20-44 . . 45-54 55-64 65+ 65+ Total Population 24,544,000 24,544,000 8,065,000 6,340,000 6,340,000 5,670,000 5,670,000 44,619,000 44,619,000 Cases 883 2979 6254 6483 16,599 Rate per 100,000 100,000 3.6 36.9 98.6 114.3 37.2 It is apparent that these apparent rates compare compare favorably favorably with those for the asbestos miners as shown in Table 6. Still United States were obtained frofrmom the American Cancer American American Cancer Society Society Society and and for males these were 25.3 per 100,000 in 1953 and 26.0 per 100,000 in 1955. They are not identical with the rate calculated from of the office of Vital Statistics but this is possibly because Cancer Society rates are for males of all ages compare favorably with the rates of 25 or among the asbestos miners 34 for total cases obtaining 65 65 - Returning to comparison between the asbestos miners and persons who are exposed to asbestos in one form or another as discussed distinguished from the general population groups just who have no exposure an interesting observation can be developed by de- duction duction 122 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 number be assumed that this 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 years of exposure has thus been accumu- lated and this figure can be divided by the approximately 150 cases of lung cancer with asbestosis reported during the year period This gives a rate of 15 per 100,000 which is at least indicative 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 unexposed persons 65 Comparison Between Eight Counties Adjacent to the Asbestos Producing Areas and Eight Selected Counties To compare lung cancer mortality rates in the counties surrounding the producing areas with another group 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 Montmagny Pormeuf Richlieu RiviereLoup 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 Beauce Drummond Frontenac Megantic Richmond Sherbrooke and Wolfe Table 25 shows the number of lung cancer deaths for the years 1950 through 1955 1955 1955 for for each of tthheseestehese these 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 producing producing producing producing producing counties counties counties counties counties counties subtracted subtracted subtracted subtracted subtracted subtracted subtracted subtracted subtracted . 3e- 3e- 3e- cause of its unique lung cancer death rate Montreal er isle de Jesus Jesus has also been listed in order to provide further comparison compari. son - : Number 000 OO! aed SZ aiey Counties Counties Countles ro9ue9 leus Counties tod 000 6 st r 6 8'6 9 22 a3ey OOL TIL SI SS 8 2 reol Lung SS6L Lung Cancer PopulationAdultMale ajep 1952 13,10 97.60 lst ig TABLE 25 Deaths Deaths Rate per < 91 < 1950 81 Male 6 1951 1952 me | ot <- 9 2 9 1,9801,98,0 WW 2561 Oot 009 220 245 Et "26 eg O61 1,10,00 .236 8'E2 < 7e * OLSt OLL oTFE S22 10,00 Man = Cancer Cancer 1953 1954 3 2d 16, I t 303 303 001 FOE 287 ,lwoIC(py, ,juaopy, Jesu 3 RAPUNOT 192AAD 185 ap PETE Ayunog DIVNG IAqanw aTR~ Tie) pasqa JO jo ya onuedsay WOT Wy Fe-4 MIUTADI CT DIUADG MItg pRaqudy Ye) *Qz afr aoye poranoe myjeap sgouvs Funt oper pew yey) . 1 paiuner wrap 4 Itis apparent from the table that the lung cancer death rate for the eight counties immediately surrounding the asbestos- producing 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 Montreal The figure for 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 be expected to basis of be about the other years 1950 200 greater and this would and 1951 deaths would result in a rate of 40 per 100,000 The only possible conclusion from this comparison is that there is no evidence that the persons who live in the counties surrounding and adjacent to the producing areas have any anay ny greater incidence of lung cancer than those who live elsewhere in the Province Discussion of All Recorded Lung Cancer Cases Living and Dead at Arlestos Arlestos and Thetford Mines Although a simple enumeration of all the known or suspected cases of cancer of the lung in these areas has no particular value from a statistical point of view it is of interest to summarize 69 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 mine cases occurred at Thetford Mines It is somewhat surprising that there is no record of any lung cancer deaths among the Asbestos group in the interval preceding the beginning of the study and equally so that no cases have been reported in 1956 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 date 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 ray only In addition there are now living four cases in which the diagnostic evidence is strongly suggestive of lung cancer This is a total of 33 cases of all types including 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 Mines and only three at Asbestos all of which occurred during the period of the study The proved cases averaged 59 years of age at death and varied between 37 years and 68 years . Their working span covered 70 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 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 was present in 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 asbestosis 72 72 Author Merewether Wedler Wyers Lynch & Cannon Gloyne Totals Asbestosis Deaths 344 92 115 40 121 712 Cancer , of Lung 55 15 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 ; a relatively small and very selected group of cases 63 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 ^'arlier 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 of these operations Cohorts were defined according to certain cri- teria and all workers who met these criteria were included in the study Through their medical records data relative to their charac- teristics were collected and their status at the end of a year period of observation was determined In the case of those who had 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 137 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 -- 74 74 were found to be smokers within the definition of that term as used in this study Thirty percent of the cohort were more than 45 ry 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 100,000 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 would 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 the other hand the study indicates that cigarette smoking is 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 reporting of asbestosis cases The incidence of asbestosis 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 of the recorded cases of asbestosis in this study developed lung cancer a figure slightly lower than those quoted by authors who confined themselves to this type of comparison ry 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 the miners is not significantly greater The rate for proved cases among the asbestos miners 25.5 per 100,000 compares well with the rate of 22.5 per 100,000 for the rest of the Province and 20.3 per 100,000 for adult males throughout the Dominion of Canada It also compares satisfactorily 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 comparison it would appear that the world 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 producing areas and in which it is presumed most 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 for the remainder of the Province and much lower than the rate for Montreal Since 1940 there have been 19 cases in which the diagnosis of primary cancer of the lung may be considered to have been proved Approximately half of these cases were associated with as- bestosis All but one died in the recognized cancer age and at least 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 Despite this the results suggest that a miner who develops the disease asbestosis does have a greater likelihood of developing cancer than a person without this disease We suspect however that under- reporting of asbestosis cases had led to a fallacious finding finding 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 lower than in some urbanized areas areas areas areas ~ within the Province 77 77 . The present study indicates that the effect of cigarette smoking is a much more important consideratioin the production of lung cancer than is exposure to asbestos and in this respect it tends to confirm recent studies dealing with the effect of smoking The value of this investigation would be considerably en- hanced by continuing the observation of the cohorts formulated herein on a year basis is strongly recommended that the chest rays of all workers be submitted to an independent reading for the diagnosis of asbestosis since an inaccurately low incidence rate for this disease creates an artifically high relative incidence for lung cancer o - VII BIBLIOGRAPHY 1. Adler I. Primary malignant growths of the lungs and bronchi London Longmans Green & Co. 1912 p.39 p.39 2. Alascio Escobar R. Bronchial carcinoma review of two hundred cases J. Internat Coll Surgeons 26 375-379 September 1956 3. Allen M. 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