Document 99M9KBrXqz9ogkom02837LEJ5

Reprinted jrom the A. M A. Archives of Industrial Health June 19SS, Vel. 17, pp. 634-653 Copyright 1958, (>_v American Medical Association An Epidemiological Study of FROM INDUSTRIAL 4400 Fifth hygiene foundation Ave- Pittsburgh 13. Pa. Lung Cancer in Asbestos Miners DANIIL C tuum, M.D., aT. DAVID TAUAN, M.A., AftNfcvrph Ever since the pronounced increase in the incidence of lung cancer among males became apparent, there have been attempts to associate it with one or another of the various elements in the environment of man The approach used by some workers has been to suspect one or several sub stances and then set about in an intensive search for lung cancer among persons who have had any exposure to those materials. In this connection. Smith ** writes: "The tendency of authors reporting the coinci dental occurrence of primary lung cancer with silicosis or with any other theoretical etiologic conditions, has been to emphasize the percentage relationship in extremely small series of cases, with control cases which are not in any way comparable." It would seem inevitable that asbestos should come under scrutiny in this manner, because prolonged exposure to this material is known to cause a specific type of pneu moconiosis, and because persons who show this form of pneumoconiosis often come to autopsy and provide a ready source of material for study. It was in this wav that reports of the simultaneous occurrence of lung cancer and asbestosis began to accu mulate after the rqvort of a case by Lynch and Smith** in 1935. Within the next 10 years, about 15 additional cases were re ported, and in 1954 Merewether79 reviewed all deaths from asbestosis recorded in Eng land since March, 1924. Lung cancer oc curred in 16% of these cases. Gloyne,41 Accepted for publication Jan. 20, 1958. This study was made possible through a grant from die Ouebee Asbestos Mining Association. Medical Director (Dr. Braun) anil Statistical Consultant (Mr. Truan), Industrial Hygiene Foundation. 634 whose work is also frequently referred to as establishing a connection between asbes tosis and cancer of the lung, reported in 1951 that cancer of the lung was present in 14.1% of asbestosis cases examined by him. In 1941, Nordmann and Sorge78 claimed to have produced lung cancer in mice which they exposed to asbestos dust. Since 1951, additional cases of cancer of the lung coexisting with asbestosis have been reported, and, according to HueperM about 100 such cases had been reported up to 1955. As a result, an association between the two diseases appears to have been ac cepted by many authors, and several writers were using the term "asbestosis cancer" of the lung. Werber,** in 1952, stated cate gorically that in 7% to 17% of cases of asbestosis, after a latent period of about \Yi to 20 years, carcinoma becomes estab lished in the lung. On the other hand, not all authors ac cepted this alleged association without reservation. Saupe*0 in 1939 reported that he had discovered no cases of lung cancer among 620 cases of asbestosis which he had examined; and in 1942, Holleb and Angrist4S expressed the opinion that the number of cases of asbestosis with lung cancer was too small for statistical evalua tion. In 1947, Wegelius ** reported 126 radiologically diagnosed cases of asbestosis among 476 workers in Finland, and found no cases of lung cancer in this group. Goldblart and Goldblatt in their section of Merewether's latest book,44 state: "But at no stage in all these impressive researches was any clue obtained which might have offered any support to the possibility that asbestos could act as a carcinogen. There &%*/ / / r/eZO Os*** "//>/*? t,r\C CANCER IN ASRIiSTOS MINERS is nu reliable critvriun by which one cats .uiiiciiiatc carcinogenicity and, as is wcl! known, relatively minute changes in the structure of a chemical carcinogen are suffi cient to diminish or eliminate carcinogenic action. If asbestos is indeed to be regarded as a carcinogen, the need is felt to demonstrate some property which can be regarded as something more than inertness." These authors advance the theory that, omit some more experimental evidence of direct carcinogenesis by asbestos of a decomfiOsition product of it can be obtained, asbestos might be considered as a "co-car cinogen" which only induces a further de velopment of a preneoplastic condition brought about by something independent of the asbestos, such as an endogenous factor. Thus the literature, while tending to sup port the thesis that asbestosis is in some way related to the development of lung cancer, is by no means unanimous. Alto gether, it is perhaps more confusing than enlightening. A careful review shows that the majority of the reports are clinical and not epidemiological. They lack many ele ments necessary for the application of epidemiological techniques to their content, and most of the authors do not make claim to having done so. What has happened is that succeeding authors have drawn conclu sions ami generalized beyond the sco;e of the works which they quote. Nowhere, for example, have we found references to a population of asbestos workers, although several authors who have quoted the ob served incidence of lung cancer in uutopMes of persons who also had asbestosis imply that this incidence applies to asbestos work ers, generally. We have likewise been unable to find any study which actually calculated the incidence of lung cancer among a population of persons who had asbestosis, and not just those who cmie to autopsy. With the exception of a paper by Dolt,23 none of those reviewed gave am data on x|>osurc and dust concentrations, and even Doll's paper merely mentions "scheduled" areas, by which is meant, "those areas where processes are carried on which were scheduled under the Asbestos Industry Regulations of 1931 as being dusty." . There is, furthermore, a complete lack of definition of terms as used in the pub lished literature. For example, the term "asbestosis," as used, may refer to changes observable only by microscopic examination of the lung tissue, or it may mean a radiotogically detectable condition. Most of the published reports obviously included women among their cases, but some of them do not give the number or proportion of women involved in the study. There is also a lack of uniformity as to what type of exposure most studies have dealt with. Of 99 cases enumerated by HneperJ* in 1955, only 10 appear to have originated in the United States, and 7 in Canada. Some of the earlier reports ap parently included asbestos miners, but it can be assumed, since 82 of the 99 cases had originated in England, and since no asbestos mining operations are carried on in that country, that most of the reported cases have involved workers in the textile or fabricating industries. Such factors as smoking habits, family history of cancer, length of time in the industry, and age of the individual case are also notably absent in the majority of these reports. With thi- understanding of the liinit2<>f ihe existing literature with respect io epidemiological generalization, it may be oi value to consider in somewhat more de tail tome representative earlier publications, a few of which were referred to briefly above. One of the most detailed studies and one which deserves the most serious considera tion is that reported by Doll13 in 1955. This study reviews causes of death among asbestos workers based on coroners' rec ords. H alx' attempts to estimate the risk by studying records of men who worked for at least 20 years in exposed situations. Broun--Truon 635 A. M A ARumt.s lit IXlirsTRI.AI. HI.AI.T1I Doll concluded that lung cancer was a spe lung cancer in other forms of pneumoconio cific industrial hazard of certain asbestos sis \jas 6.7%. and in 169 cases which workers and that, after 20 years of expo proved not to have any type of pneumo sure, the risk is 10 times as great as for coniosis it was 8.3%. Gloyne considered the general population. "the mortality of the asbestos workers" to This article is important for several rea be "disturbing." First of all, it is obvious sons, in addition to the definite conclusions that the paper does not deal with the "mor at which it arrives. For example, it begins tality of asbestos workers," and secondly, by stating that "in view of the infrequency it must be borne in mind that all of Dr. of asbestosis, this large number of cases Gloyne's cases were submitted to him for (61 cases of lung cancer) suggests--but study because the findings were unusual does not prove--that lung cancer is an for uncomplicated pneumoconiosis. It can occupational hazard of asbestos workers." reasonably be assumed that cases, including Neither this article nor any previous one those of asbestosis, in which the findings which we have examined presents any fig were not considered unusual were not sent ures to prove that asbestosis is an infre to Dr. Gloyne for examination. As a mat quent occurrence. Estimates of the number ter of fact, in the same paragraph in which of persons potentially exposed to asbestos he expresses concern over the incidence dust in the United States alone vary from rate in asbestosis, Dr. Gloyne himself 10,000 to 35,000, and the incidence of as (joints out that the rate for lung cancer bestosis of any degree might be higher than based on necropsies at the London Chest Doll imagines. Hospital was 21.3% while the figures of This study, like so many others, involves autopsy records. The number of persons involved in the statistical analysis is only 113, representing only 1,042.25 man-years of life. It is also true that in selecting men who had been employed for at least 2(J years, the study automatically excluded those who died from other causes after shorter employment. Another reason why this publication is of importance is a statement which it con tains to the effect that ``the strongest evi dence that it flung cancer) may be a hazard (in asbestos workers) has been produced by Mtrrewether and by Gloyne-' In 1951 Gioyne 41 presented a review of 1205 autopsies on persons who had worked in various dusty occupations. This number included 132 asbestos workers, of whom 121 showed "pneumoconiosis"--pre sumably asbestosis. Primary cancer of the lung occurred 17 times in this group, an incidence rate of 14.1% for lung cancer among asbestosis cases coming to autopsy. the Registrar-General showed only 2.4%. He thus recognized that autopsies on a cer tain selected gTOUp of cases were not rqresentative of the general population. It would seem, then, that notwithstanding the value of Dr. Gloyne's work, its im]>ortance as an index of the prevalence of lung can cer in asbestotics has been misinterpreted by some who have quoted him. All that it really shows is the fact that in a group of 121 case*, selected for special studv pri marily Ijccau.-c they seemed abnormal bv preliminary examination. 17. or 14.1G had lung cancer Mercnethe' m 1^47. ;:i thi rtqxirt of trie (."art !t'veetof I-actorio. reviewed all castv- rcj>rted between 1924 and 1946 in which asbestosis was the cause of death or a coexisting condition. This work was later extended to include all such cases relorted up to December, 1954. by which time there were 344 deaths, including 205 males and 139 females. Among them were 55 cases (16%) of cancer of the lung. 41 in There were in his series 796 cases with sili males and 14 in females. It is quite possible cosis, and 6.9% of these also showed pri that a large number of asbestotics who did mary cancer of the lung. The incidence of not die of their asbestosis, or in whose 636 I V. IT, June. 19.W AV use c.Axcr.R /.v asbestos misers death certificate it was not mentioned, may prior to that date ami enumerated a total have been missed. The import of this 16% ` of 99. Eleven of these were those dis is enhanced by the simultaneous statement cussed by Doll24 and may have been cases that the incidence of lung cancer in autop covered by other authors. Eight were dis sies of the general jxjpulntion is only !% covered by Kennaway and Kennaway in The danger of attempting to compare a an analysis of death certificates, iuid, unless rate found in 344 cases with the rate for Merewether's study was incomplete, these the general population without respect to cases should have been included in his re age, occupation, and many other variables, port. Of the remaining 80, it is quite pos such as smoking habits, is obvious. sible that the 31 contributed by Merewether Lynch," who with Smith** had reported the first case in 1935, reported 4 cases of carcinoma of the lung in a series of 49 and the 17 by Gloyne contain some duplica tion with each other or with those of other English authors. autopsies on workers in an asbestos manu facturing plant who were shown to have "demonstrable deposits of asbestos in the -Principles of the Epidemiological Method lungs." This, of course, is not necessarily Dom * has pointed out that much of what identical with the disease asbestosis. Lynch, is now thought to be pertinent concerning himself, points out that, although this is an the comparative frequency of lung cancer incidence of S.2%, "both figures are too in different population groups has been de small for very serious statistical types of veloped from the analysis of clinical ma calculation." Nevertheless, later writers terial, particularly surgical and autopsy have used this paper to strengthen the case records, supplemented to some extent by for an association of carcinoma of the lung the reported impressions of various clini with asbestosis. It is also of interest that cians based upon their personal observa Klotz ** found only the same number of tions. More recently, however, attention cases of lung cancer in a series nearly 10 has turned to the systematic investiga times as large, i. e., 4 in 478 cases of tion of this problem by the same methods asbestosis. that have proved so successful previously in Behrens, as cited by Merewether,7* esti the study of communicable diseases, that is mated that, of 309 cases of asbestosis in the to say, by epidemiological methods. literature, 44 showed associated cancer of In order to apply this method of investi the lung--giving an incidence of 14.2^. gation to the problem under discussion, we This is an illustration of generalizing an were of the opinion that a study should be incidence obtained in a group of cases planned so as to provide (1) a well-defined which were undoubtedly reported only i>e- population group: (2) available data for all causc some of them showed lung cancer, to members of this population, including the possibly hundreds of asbestotics whose healthy as well as the ill; (3) a sample cases were never reported. The same ap which is truly representative of the popula plies to the conclusion of Teleky,*5 who tion; (4) reliable and valid observations appears to have reviewed reports of 39 relating to the problem of the study. autopsies on persons with asbestosis among which 6 cases of lung cancer occurred. In formation from sources such as these does not justify generalizations with regard to mortality rates. A serious defect, common to most of the studies which have been reported, is that little or no information concerning the healthy people in the group seems to have been available to the author. In order to Perhaps no one has written so exten draw a generalization regarding all asbestos sively on the subject as has Hueper,421* workers, it is necessary for a study to in In 1955 he reviewed the cases ** reported clude living persons as well as the dead. Broun--Truan hV /-V A. M. A. ARCHIVES OF INDUSTRIAL HEALTH Limiting the investigation to cases coming to autopsy, as has been frequently done in earlier studies, still further restricts its use in generalization. The problem with which we are concerned is whether asbestos miners experience more lung cancer than does the general population. The answer necessitates the collection of reliable infor mation on asbestos miners as a group, as well as on the general population. It seems advisable to discuss the differ ences between the epidemiological approach and that used in the studies which have been reported to date. A very important consideration is the fact that lung cancer, in spite of its increasing numbers, is still a disease of low incidence; that is, in a given population not many persons will contract this particular disease. This fact requires that large samples or groups must be stud ied to provide meaningful results. Recognizing the difficulty of obtaining such targe samples, most earlier writers deviated from the epidemiological method and sought to circumvent the requirement of observing well persons by (1) compar ing the relative frequency of cancer in vari ous sites; (2) comparing the relative frequency of cancer in a group of hospital ized patients; t'3) comparing the relative frequency of cancer in a group of cases coming to autopsy. Attempting to compare two imputation groups, looking only at the relative frequenev of cancer in various body sites. :nav resuil in finding a higher percentage 1 relative frequency i in one of the groups, `..hen if. fact, the iroetaiity rate of cancer of a particular organ is exactly the same m both groups This is very clearly dem onstrated in the excellent article by Dorn.30 The mortality rate from a particular cause is the true measure of comparison. It is apparent that selected groups such as hospitalized patients or autopsy cases may not be in any way representative of a larger group, and that in dealing with such samples, the observer may easily find more cases of a given disease than would 638 be found in another group of the same size, but representative of the general population. It is true that investigation of cases from such a sample can furnish information valuable for research, but the use of this information in drawing generalizations is necessarily restricted. It is the obligation of both the investigator and of those who read his report to make proper comparisons and to draw only those conclusions which are valid and justified. A good statistical study of cases of cancer of the lung occur ring in a group of autopsies can lead to a proper inference concerning the frequency of lung cancer among cases coming to autopsy, but only to such cases. For in formation from such a study to be pro jected to some larger group, it is necessary that the autopsies represent a good sample of that larger group. To assume that such is the case in any particular series is dan gerous and likely to be false. There is some danger that the figures rqwrted by some authors may be miscon strued as applying to asbestos workers or even asbestos miners, when, in fact, the authors in question do not make this gen eralization, nor can the generalization be made for the reasons stated. Close study of the reports reveals that the percentages cited relate only so the group of autopsies covered by the particular investigation. The present study, in contrast to the earlier works, has been planned to utilize the epidemiological method. A well-defined group of asl>estos miners has been estab lished in such a way that it constitute? a ">>od -.ample of the whole population of asbestos miners in QucIh/c. Data for ail members of this group have been collected and analyzed. Those concerning lung can cer have received most careful considera tion. Details of the methods employed will be set forth later, but the type of approach is considered to permit of fair comparisons and valid generalizations. Collection and Analysis of Data A preliminary survey of potential sources of information in February', 1956, involved Vo). 17. June. 19SX /W /./ At; t'.-txi r.R ix Mtxi.ks discussions with the physicians in charge of the asbestos companies' programs .-mi! with clinicians. pathologists, represent lives of Citv and Provincial health dejnriinrnts and of the Canadian Cancer Society, and other interested jktsojis. Jt was found that morbidity data, although somewhat limited, were available front such sources as the hospitals in Montreal and Quebec City, and the 13 cancer detection centers in the I'rmince. However, because of the high mor tality in lung cancer, it seemed advisable to depend u^ion data relating to deaths. These we found to be obtainable at the vital statistics dqwnnictn of the Ministry of Health in Quebec City. Prom the pre liminary survey, it was apparent that exten sive and detailed information could he gathered with respect to both the ]**rsons employed in the asbestos mining industry and the mortality figures for the general population. Following this exploratory survey ihe initial effort was directed to ihe collection of data relating to all workers who had lieen processed through the clinic at Theiford Mines since its inception in 3947. and similar information regarding all workers at Asbestos. Que. Data Pom the clinical records included the age, family and |ier'onal medical historic-', smoking habits, number ot years of explore. an estimate of weighted exposure, and the course of the individual's health status nr the cause rif his death From this information it was (mssibk' to formulate a "cohort" which could tie ell defined, should be representative of the whole group, and could be followed for a definite period of time. All of the available experience indicates that the development of asbestosis in less than five years of ex posure must be somewhat rare. Accord ing!)'. the cohort was defined as including every miner who had a total ex]insure of five or more years, and who was on. the employment rolls in 1950. Office and other nonexposed personnel, regardless of length of employment, were not included. This cohort was then followed by means of the annual physical examination records through a six-year interval, 195U through 1955. All data regarding this group were then tabulated in order to determine the characteristics of the cohort. For those who survived the entire period, reference was made to the physical examination results and x-ray findings at the end of the |>eriod. Those who had died were tabulated sepa rately, and the cause of death was corroborated by examination of the death certificates. A further search was made concerning those in the original cohort who remained unaccounted for when the living and the known dead had been tabulated. They represent men who had left employ ment through retirement or resignation. Fventually. all but a small number of these were accounted for as eitheT living or dead, ;uid in the latter event, the cause of death was substantiated in a similar manner, and the result* added to the original list of deaths. Death certificates for the Province of Quebec for the years 1952 to 1955, inclu sive, were reviewed in the department of vital statistics of the Provincial Health Ministry, together with statistical sum maries of the causes of deaths in the Prov ince by counties All cases in which death was certified as having been clue to pri mary cancer of the lung were examined for such information as place of residence, occupation, da--- nf death. hospit;-.' in which death occurred and whether or not an autopsy was performed. Cases in which lung cancer was given as a cause of death, but in which it was not specified as to whether the cancer originated in the lung, were also reviewed in an effort to include all instances of primary carcinoma of the lung in the study. The statistics for the Province of Quebec relate to population, total deaths from all causes, total deaths from cancer of all types, and deaths from lung cancer. These were collected and tabulated by counties and by sex for the years 1950 to 1955, inclusive, Braun--Tman /*/ ,-j. m. h AKcmrr.s or industrial hl.-u.tii From them, death rates for the general population of Quebec and of individual counties were calculated for specific years and analyzed by cause. Practically all employees of one company are covered by a group policy of life insur ance which, fortunately, nearly all of them continue to carry when they retire. A very few are not covered by this policy, and those who leave the industry for one reason or another except retirement usually are no longer covered, but this is likewise a small number. As an additional check upon the information obtained from the clinical records on this group, .the records of the life insurance company were examined for all death claims paid under the policy, and particular notice was taken of the claims in which the proof of death was based on cancer of the lung. Deaths from lung cancer among asbestos miners were thus determined from the clinical records in the medical sen-ice of the industry and checked by means of the death certificates and insurance company records. "I~he deaths were then verified individually oy reviewing them with the physicians in charge of the medical services. In this man ner, there w-as 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 calculated using both the "proved" and the total of "proved" and "suspected" cases during the years un der observation. Comparisons were then made between the death rates from the same cause among specific segments of unex;>osed persons. All lung cancer deaths, both suspected and proved, were carefully ana lyzed to determine possible relationship or correlations between the development of lung cancer and any factor know-n from the clinical records, such as family history of cancer, personal history of heavy smoking, coexistence of asbestosis, or exposure to asbestos. In addition to this analysis of deaths oc curring in the cohort and during the years under observation, every known death from cancer of the lung, as w-ell as every case diagnosed but still living, has been tabulated and analyzed. They will be discussed separ ately from those included in the population and time-interval under study. A comparison of lung cancer mortality in the asbestos-producing counties has been made with that in counties which are far removed from the asbestos mines and in which, presumably, no asbestos miners live. Finally, in order to broaden the compari son of death rates in different population groups, the rates have been collected for Canada generally, and for the United States, according to the most recent published and unpublished material. Results and Interpretation The cohort which was constructed accord ing to the criteria described in the preceding section has been considered individually and compared with the general population. Description of the cohort will be presented here as a preface to the results of the study Original Cohort Lost Pervwis DnJuctfd Final Cohort Living in 19SS f worktop *>nl ffiirvti) 1 *rad by J 9 5 5 Cancer of lung cance-r or Other ciuw* i'nttwwfi SnhA^rs \on*inokr ri ('nkiiowit *.09* t33 5,,9S8 S.771 IS7 9 3 169 6 4,673 1.263 20 Tables 1, 2. a. and -1 r -c-eu; .'igc. nuMiber of years of employment weigh1 cd average cx|insure, and smoking habits of the cohort. A comparison of the exposure to asbestos dust is presented in Table 3. All members of the cohort were placed in one of three categories, representing increasing degrees of exjiosure based on a weighted average of the years s|>ent at various levels of dustiness. The degree of dustiness for each job category was determined after consulta tion with persons familiar with the environ ment and conditions in the various work Vol. IT, /am-. JV5X A*/ lung cancer in asbestos miners Table 1--Number and Percentage Visit ibulion Table 2.--Number and Percentage Distribution by by Age i Length of Employment Ate 30-44. ....... iS-H*,...................................... ......... ii-M.,... *.............. -............, _____ ft$+............................................ ......... UtHUkQlt&L^.................. ....... Touli......................... ......... A.*cfct A.,........ .................. Number J.flO! M34 6U m 3 S4SS * Lee tli*s 6A%. Pet Cent *6 IV 10 5 Lenttb of Employment ................................................. ................................................. 30-39............... ................................. ................................................ 40-4V............................ ,................... NH-.................................................. TouU,................................. A rente iwi of employment_____ Noaccr 1.389 Z39 ra <09 4i s,* it F Cent to 40 )ft to l 1 100 areas. For the purposes of calculation, the assumption has been made that the relation ship between these categories is linear, and that Category II is twice as dusty, and Category 117 three times as dusty as Cate gory I. ually smoking more than five cigarettes per day. Persons who smoke pipes or cigars exclusively were not considered to be smok ers lor the purpose of this study. Table 5 presents the year-by-year ex perience of the cohort and indicates the Table 3.--Number and Percentage Distributism by Exposure Category ECiepwoteourjrrt UmntIkl...n...o......w......n.....,.................................................................................... ... ... A renteTEatpeali*.u..r.e.................................. Number 1.031 40 Per Cent 33304f*t too ` Lot thin o.J%. Table 4.--Number and Percentage Distribution by Smoking Habits Smokinf Baoiti Smourn........ .............. Nonjmokerl................ Unknown................... Touh............. Namber . v*n . 1,363 . 30 . &BS4 Per Cent 7ft 31* vn * Lets this oj%. The fourth variable, smoking habits, was similarly tabulated and is shown in Table 4. This was included because the informa tion was available and because smoking was regarded as one of the variables which, besides the environment, could conceivably influence the development of lung cancer. As used in this presentation, the term smoker refer; to a cigarette smoker, habit- number of deaths each year from specified causes. In general, a case was considered to be "proved" as one of primary cancer of the lung vvhen the records showed that the diagnosis had been supported by an autopsy or surgical resection of the lung with microscopic examination of the re moved tissue. In one case so considered, however, diagnosis was confirmed by bron- Tabll 5 -- /co^-av-year Experience cj Cohen and Death Rotes per J00.000 Man-Years of Rise Cetue of Deetb TCmt No, Alive At Bettuntoe ot Veer Pruned Unwary Cft. of Luftt Suspected Primary C*. of Lunt Other Ctuie* 1950............................. lftil.............................. tfttt....................... .... J953....................... W44..................... . 1955.......................... i.fttt 5,942 i.W5 1 3 0 3 J 3 3 12 0 17 0 37 1 34 0 93 0 3ft Ttnl......... ft "Proved" nie per 100.000 trwn ycan of mk- fsjjp'i j--" 34.S 3 m Unknown l 1 0 0 4 0 ft Mftn-Yoftrs of Ri*fc J.930 i.Mi i.903.5 SMA 3.8W J.7S04 jj.m.s Toni" nu per 100.0UO aun.ywn ol nU - --" MB Braun--Truttn /V o A M. A ARCHli 'E.'> Of INDUSTRIAL HLAI.TH Table 6.--"Preyed" Cam of Prnnary Cancer of the Lung Cue So. I 2 3 4 6 t 7 a 06 66 66 6ft 4S 61 66 a? 66 Smoker Yes Yes Yu Yet Yes Yes Yes Yes Yes Eiposure 36 jt. to Cel. 11 64 3? jytr.. to id Ctc. Cat. 1 1 12 yr. io Cat-1 22 yr. la C*l. H 33 jt. id Cel, 111 3017. la Cel. tt 16 yr. la Cil. 1 58 yr. la Cat. Ill Died 30-12-Si 6- 3-66 7-20-65 6-20-60 -61 4-30-63 11-23-63 6- 6-64 6- *66 Autopsy Yes Yes No ^ es Yes Ye* Yes Yes Brooch, Yu NO No No Yes Yes Yes No No choscopv with visualization and biopsy. In another, although there was no autopsy, the diagnosis of primary cancer of the lung seems to have been beyond question. The term "suspected" primary cancer of the lung was applied to those cases in which the diagnosis remains in doubt but some of the evidence points to cancer of the lung. There were three such cases. The term "man-years of risk" has been used to mean the number of men at risk for the year under observation. A person who lived throughout the year was counted as a full man-year of risk, but one who died during the year was counted as one-half a man-year. Deaths occurring in the cohort, and in which lung cancer is considered to have been proved as a cause, are shown in Table 6. In Table 7 are shown three deaths which have been considered as "suspected" lung cancer cases. An indication of the importance of these "suspected" cases in interpreting the results of the calculations is desirable before fur ther discussion of the mortality rates which are deri-.ed in later tables For example, it happen; that the rate found tor the proved cases is close to the "expected" rate based on the general population figures for the Province, as will be shown later, and on this basis we should find eight deaths from lung cancer among the cohort. Actually, nine cases were observed. If, however, the 3 additional "suspected" cases were in cluded, increasing this figure to 12, the total would be very close to the 95 5c level of significance. However, having found, just 12 cases, we are not above this level, and therefore the hypothesis that asbestos miners do not have a higher mortality from lung cancer than does the general population can not be rejected. Nevertheless, the occur rence of 12 cases in this sample would increase the rate to a point which approaches the significant level. Because of the tre mendous importance of the questionable cases in this respect, some detail regarding them will be given here. In one of these cases, the suspicion of cancer of the lung is based upon the x-ray interpretation, and, although no autopsy was performed, the death certificate indicates that death was due to lung cancer. It is well known that the x-ray appearance of fibrosis, especially if a localized density or a superimposed tuberculous lesion is pres ent. can simulate that of a tumor, and by itself, does not justify the inclusion of this case as one of "proved" cancer of the tiuig A case was certified as having died by <w;iw>n of hydrothorax. possibly due to lung v<r but agam there was no surgerv ano ns. postmortem examination. In th*- third cn-a.. although it was subjected to autopsy, two pathologists disagreed as to whether lung cancer was present. The death was certified as having been due to chronic myocarditis with nephritis and pulmonary congestion, and possibly cancer of the lung. On the basis of these facts, it seems unwar ranted to include these three cases among Table. 7,--"Suspected" Primary Cancer of the Lung Cue No. 1 3 3 Alt Aft 46 66 Smoker Ye* Yes Y Eipmrn M yr. la Cet, tit M yr. tn Cet. lit yr. is Cet. n Died 10-26-60 7- *63 *-30-66 Autopsy No Ye* No Aibettoo* No Ye* No 642 Vol. 17, June, mg ? ef'-L b /.( A<; L'.I.VCCR ;.v ashi-sto^ miki-.rs "proved" instances of lung cancer. On she other hand, the)' cannot, in fairness, be dis regarded completely. It is for this reason that mortality rates have been calculated (aith ways. Table 8 gives the rates by age groups. The rates by length of employment are shown m Table 9. During the first 40 years of employment, the rate rises, an observa tion which seems plausible since the men were growing older. However, after 40 years of exposure there are no "proved" rases reported for a total of 240 men dur ing the six years, or about 1440 man-years of exposure. When the "sus|>ected'' cases are added, one case does show up in this T-sri.e 8.--Lung Canter Dealtr.t by Age Groups Table h--Lung Cancer Deaths by Length nj Employment Number of Perwirs anj Number of Lunt: Cancer De*ih- l-eneih of Employment. No. of I'WSOIU . No. of Deaths proved Total 5-0............................ WM9......................... , TthT*............................ ............ . 4fl-4y........................ +................. .... i.rw 2.3W 022 603 ISS 33 0 1 3 5 0 0 0 1 3 7 l 0 Totals ... 3.V& 0 17 Annual I.une Cancer Death Ralci per 100.000 Man Vean i Exposure l*ntth of Employment Proved Total 5-0.................. .... . 10-10............................... ................ 20-29..................................................... 30-39................................... ................. 40-40..................................... so+..................................... 0 ? 54 138 0 54 193 90 0 Over-all.................................. 25 34 Number of Person* and Number of I-umr Cancer Death* Ace Group * No. of I'enORf No. nf Deaths Toil 20-44................,, ... 45-54....................... .. Hi-64.................................... . ... l nknown....... . . . 3.901 1.124 *13 313 3 1 1 3 4 U 1 s 3 5 0 Totals.... ... 3.955 0 17 Annual T.un? Cancer Death Raie net 100.000 Man^ ears of Exi*>*ure Aft fniuii 20-44.......................... 45-54... . .. 55*4H........................................ ... M+ .................. .. Vtiknuv'ii................ . I'rOMrrl 4 13 *1 717 (i Total 4 44 fc) 2A3 n U'cf-uSl... ... .... 25 34 i>cnu<l Thi- uoultl produce a rale of 69 per 1D0.U0U, again demonstrating the im portance of these questionable, but un proved, cases to the final conclusion, liecausc. if there were no cases in this number of men with long ex|tosure, and if asbestos is a carcinogenic agent, it must be concluded that these 240 men have demon strated considerable resistance. This is a bio logical phenomenon which has been observed previously and is consistent 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 18, which appears later in this section, in- dicates that the members of the cohort did not die from lung cancer at a younger age than the general population. The rates by weighted exposure are shown in Table 10, and it will be noted that they present strong evidence against asbestos taring a carcinogenic agent, for, it exposure to asbestos is in any way con nected to lung cancer, we would expect that the longer and heavier the exposure, the higher the rate that would be found. The only possible error in this interpretation could occur it the weighted exposures were inversely related to years of employment, Tahi > K1* -- f.nwt; t'arifiv Deaths by Exposure Number o; P-'m- n*. ani! Number iit Lunc Cancer Deaip<- Exposure Category I'ersons No. of Dtnths Proved Toul l............ .. If......... ........... . . Iff.......................... ... Unknown.,........... .... 2.031 2.150 1.772 5 4 3 2 0 4 4 4 0 ToliU........ .. 3.958 9 12 Annual I-unjr Cancer Death Rates per 100*000 Man Year* of Exposure Exposure Category Proved Tola .!!1 .......................... [II............... Unknown..... . 33 33 33 31 19 37 00 Over-all. 35 34 H rntm~Truan /'-V / i 7^-d A. M A ARCHIVES OF INDUSTRIAL HEALTH Taw.? 11 --Number of Renans in Furious Weighted Exposure Categories by Length of Length of Employment weighted Einnture CalMOrtM f II hi 5-0 10-19 20-29 4 (MS 504* 7t7 593 400 663 m 851 1U 363 243 747 216 13: 76 67 41 X 21 10 TWU rail A write veer* of eipesure j:a 2.150 17-S 1,772 16.6 fcix>w*n 0 1 2 1 l 0 3 29.0 TouJ 1,79$ 2.396 922 603 I6& 65 5,968 in which case the heaviest weighted ex posure (Category III) would show the shortest length of employment. Table II, which lists the number of persons in various exposure categories by length of employ ment indicates that this error has not oc curred. In fact, the average number of years of employment for each exposure category' is almost identical. Table 12, which develops the rates for smokers and nonsmokers, is most striking. It shows that not a single case of lung cancer developed among the 1265 non smokers and that all cases of lung cancer, both "proved" and "suspected," occurred in smokers. Table 12 was so striking that it was felt that funner verification was necessary. It was possible that some abnormal distribu tion may have occurred, e. g.. the non- Tasle ij --A'umbrr and Percentage Distribution Smakere and .Vmjmnfcfrj f>y Age Groups Table 12.--Lung Cancer DeaJh for 1 Smokers and Nonsmokers Number of Persons and Numb** { Lorn Cancer l>etbi by Smoktnc Habits No. of Deaths Persons Proved Toul Smakers............. ........ . Nonsmoteen.. . UdXdo 4.673 1JC6 20 9 0 0 12 0 0 Toull........... 4,841 9 It Annual Lung Canter Death Hates per 100.000 Min-Vein of Exposure by Smoking Habits No. of Deaths Smokers...,,*........... ............ Noosmokers......,........... ,,* Unknown_____ ____ ... ............. Proved 0 Total 43 0 o Oeer-ell................... 34 smokers may have included a larger percentage of young men. Consequently, ad ditional Tables, 13, 14, and 15 were con structed to show the distribution of smokers and nonsmokers by age, length of employ ment, and degree of exposure. Although there are slight differences, they do not account for the fact that all observed cases of lung cancer were in smokers. In respect to age (Table 13) the combined average age of the smokers was 4.9 years less than that of the nonsmokers. Table 14 show; that as far as length of employment is con- TablC H--\!umber and Percentage Distribution of Smokers and S onsniokcrs hy Length of Employment .-M . T.*--`-4 . .. ... i r.Cnou n.. . . . Totals...... . Affnet ase............ , Number Smokrr NonsmoVer 3.?* fW 411 IU 2 4,673 393 224 202 150 0 -- 1.266 44.2 Unknown 13 4 2 1 1 -- 30 40.7 Empionneni 3-9......... ................... 10--19............................ 20-29............................ 30-39........................... *0-49............................ 504*.............................. Totals...... .. A verm toarth of id element............. Smokers 1.40? i.or,: 722 433 no 33 ---- 4.673 17-0 Nonsmokeri 377 42* 19* 1*> 73 <ys -- 1.265 19.3 Unknown 10 4 2 4 0 0 *_ ?o 16.0 Femauit Distribution At? Group Smoker 20-M.................... <5sV-6m4.................................................. 95* ........................... UrttPo^Ti.................... is.2 S.g 3,s Konsmoker M5 160 itj 0.0 Totals............ 100% 100% Unknown *0.0 J.Co.0 yo 6.0 -100% Less then 0.05%, <U4 Percentage Distribution Uncth of Employment Smoker Noninraket 6-9 ......................... 10-19......................... 20-29......................... 30-39......................... 40--49......................... ... +........................... 2,4 MS 33.7 16.7 ll.l 6.9 U Touli......... .. 100% 100% Unknown 500 20.0 10,0 20,0 o.O 0.0 100% Vol IT, June, I95S LUNG CANCER IN ASBESTOS MINERS Table 53--and Percentage Distribution of Smokers and Nonsmokers by Exposure Category Exposun Cetefory 1............................... n............................... m............................... Unknown.................... Tottli............ ^rrc arposure cautery........ . Number Smokers Nonamoten 1,663 1.691 1.426 4 474 433 133 1 4,673 1,363 1.0 1.9 viokncvo 4 7 9 0 30 U Potcbui* Distribution Exposure CBtctory Sunken N'onxmoJtttS I.................................... II.................................... UIUnl.s..o..v..p................................ 33.1 36.! o.i 33.7 0..71 Tttttls............ 100% 100% tlolnowg -0 M.0 04.30.0 100% cemed, the smokers had worked about 2.3 yeaxs less on the average than the non smokers. With longer exposure and greater age, one would expect the nonsmoking group to show a higher rate if lung cancer were due to asbestos. Table 15 shows that the average exposure category was almost the same for the two groups. Therefore, this variable seems to be of no importance in accounting for this difference. The result of this additional analysis is that none of these factors appears to lessen the effect of Table 12. Comparison of the Cohort Experience with that of the Province of Quebec, Do minion of Canada, and the United States.-- In order to make a comparison of the experience among asbestos miners with that of the general population of the Province of Quebec, statistic? were gathered, a? stated earlier, m the office of the Division of Demography in the Provincial Ministry of Health. The data on total deaths, deaths from all forms of cancer, and deaths from cancer of the lung were obtained by sex and by county for the years 1950 through 1955. In addition, all death certificates which specified primary cancer of the lung, and all those which indicated lung cancer but did not specify the origin, were exam ined for the years 1952 through 1955. Table 16 gives a tabulation of the number of deaths from lung cancer in the Province and in the cohort for the years 1950 through 1955, and shows the annual rate per 100,000 in these segments. It will be noted from the table that the' mortality rate for the "proved" cases in the cohort is only slightly higher than the rate for the Province. When the "suspected" cases are included in the calculation, the rate for the cohort rises to 33.8 per 100,000, which is about 50% higher than the rate for the Province. This, it will be recalled from the previous dis cussion of the effect of the "suspected" cases on the results, approaches but does not exceed the significant level. One further interesting observation from Table 16 is the rather marked increase in the iota! number of cases for the Province between 1950 and 1955. It is assumed that at least part of this increase is due to im proved recognition and reporting of lung cancer during the interval. For this reason, the years 195-t and 1955 were' thought io be more nearly representative of actual condi tions E-. er <-. is quite likely that the genera' " r. r.^t studied tor lung cancer wr. the same diligence with which 1 i Table 16---C&tup&riton of Cokort with provmef of Quebec Persons 1M0 1961 Leaf Ctnatr D*tb 1962 l3 1964 Annual Rnte per 1966 TotkJ 100.000 Pro.UM* Cohort Torn! PW*d ProTina* i.lWi.s.mWt m 2D Ml 303 303 sit 1.624 3 2 0 3 1 3 12 1 203 l 39 1J91000 193 214 246 303 302 364 1.612 tur'iixHnS ubosun workeei) 2TB m 5.3 22.5 In the Prolific* tom. H tel tern uwcwd tU mek lone carar death* tre for mto of 20+ Teen. Approxieme aidpoiato/tlttenouttmod population tor 1941, tod tbestia*t*d population for 1964 {Rapport, D\*. de ia De* soertphk). tNdmber *Il*e In cohort at beflnninf of 1942. Braun--Truatt r*/ / -2- * Groan 30-H 3553-+64 Tauls A. M. A. ARCHIVES OF INDUSTRIAL HEALTH Table 17 -- Lung Cancer Deaths for the Province of Quebec* Population 371C73C77,..10U/000000 1,277.000 Number of Deaths 1954 Total Certified Specified Primary Total Pt4>4td Total Proved i1mw16--0770 1U3U31"630 tn4too3 191 t322"o9299 1333 Total Certified Specified Primary Total Proved Total Proved U1101i42:703 3536794 133 115_1416673 337 3_554927 152 Ate Group 20-44..................................................... 45-34...................................................... Li-04..................................................... 4H-...................................... Ostr-all............................................... Death Rates per 100*000 1954 Tetel Certified Specified frimxry Total Prosed Total Prosed M 1.7 1.4 IJt 33.2 17 A 21.3 14.4 72.0 27.7 40.4 23.4 si-7 Vi sej ha 23J 0.7 13.4 8.0 1955 Tou) Certified Specified prtmefr Total Prosed Total Prosed 2.2 22.7 83.4 172.3 1.2 17 J 4L.fi 440 2.2 27.7 *4.7 122,3 l.J 1JJ 4l,fi 440 27,3 110 *7.2 12J * Data <Totn death certificates. t Estimate lor population obtained bp applylnj 1231 peraesiates for ate croups fpr males to tbe total population tor 1234, as tlsea to Rapport, Dir. de la Pemocnppte. this disease is looked for in the miners, and it seems probable that the mortality rates tor the Province may be low. This would appear to be substantiated by the fact that the reporting of cases in the cohort showed no such increase over the same period. Table 17 was compiled to show the an nual age-specific lung cancer rate of cases in which the death certificate merely read "cancer of the lung." as distinguished from those in which the diagnosis was confirmed by autopsy, surgery, or biopsy. The term "specified primary" refers to those cases in these rwo categories in which the tumor was specified as having originated in the lung. It will be noted that, of the lota! cases reported in 1955, a much higher percentage than in 1954 were specified as primary. The table also shows that a higher percentage ot the total cases certified in 1955 were proved, again indicating increasing interest in this disease. A comparison has been made between the age-specific rates shown in Table 17, and those for the cohort, shown in Table 8. An average of the 1954 and 1955 rates for the Province has been used, since the 1955 figure was higher and may have been ex ceptional. This comparison, summarized in Table IS, shows that the observed number of deaths in our sample is not significantly greater than the expected number of deaths, based on the average of the 1954 and 1955 figures for the Province. It is true that, in the case of the age group of 65 and over, the five deaths provide a figure which is almost significant at the 959c level. How ever, it should be noted that this number includes one of the suspected but unproved cases previously referred to Furthermore, it is rather likely that the rate for the general population is understated in this age group, for the obvious reason that the exact cause of death in the very old is not Table IS--Comparison of the Actual and Expected Number of Lung Cancer Deaths by Age Among Asbestos Miners Ate Group Province Total Specified pnmarv Rai* per 100.000 30-44 45-54 55-64 M+ Unknown 14 ?<4 67.6 itJ Observed No. &Tt*ct*d ot Destfct Ko< of No. of Miners Deaths * Proved Total 3.901 1.124 615 313 3 Ot t 1 2 13 t 33 2 43 - eo Th eipecied oomter Is based on the toons* of the 1233 ere-apeetfie rates for th* Profine* of Quebec. I Actually 0-4. tod 646 Voi V, June. I9SS LCXC CAXCER ix asbestos mixers Table 19.--Age Distribution of Adult Males for Table 20--Annual Death Rates per 100,000 /.<r the Province of Quebec, 1951 * (Tourer of the Lung tn Canada * At* Oroup 30-M............... ti-SA.................... ........................... *4+ Tout.......... Province Number Jtt.Ml 12S.MA 113.46? Temnut* w 1$ U 10 1.1U.49S 100 Ptmmnt In Cohort 1 '0 0 100 * support. MM. a matter of the same intensity of interest as it is in younger persons. Table 18 also answers a question pre viously raised. It snows that the members of the cohort have not died from lung can cer at an age earlier than the general popu lation. and that such an explanation cannot be offered for the absence of lung cancer in 240 men with more than 40 years of employment referred to on page 645. Before leaving this comparison of the Province with the miners, it should be shown that their age distributions are rea sonably the same. That this is the case can be observed from Table 19. It should be remembered that the miners retire and consequently, it can be expected that the oldest age group will be larger in the general population. The data presented in Table 20 indicate that the lung cancer rate generally decreases after age 70. There fore, we could expect the rate for all people over 65 to be smaller than the rate for the group between 65 and 75. which would apply to the oldest group of miners. It is felt that by using the whole adult male popula tion. we have developed rates for the gen era! population which are somewhat lower than if we had been able to exclude the people in the general population over 75 A comparison between the asbestos miners and the population of the Dominion as a whole was made, using statistical material from several sources. In one source. Phil lips r* gave age- and sex-specific rates for Canada for three periods between 1931 and 1952. The rates for males are given in Table 20. These figures show strikingly the increase in rates between 1931 and 1952, and this Braun--Truon Are Group Under 30 30-34 4105--4349 54S04A*--54M49 00-64 t7t0--6794 1706--9749 *A&l+l Ages I93M933 00..29 3.0 3AE,2> 8.2 12*7 u.s l1,0V.7l 16.8 1f1u.4 is Oroupi of Years 1941-1*43 QJ 0.9 3.2 6.4 12.5 18.9 27-0 33.7 MA 30.6 30.0 vs HJ M 1950-1963 1.0 0-8 3.0 6.3 16.7 37*2 39.7 77.8 102.9 86-3 S3.9 59.7 71.0 13-8 * "Mortality from Luhs Cancer in Canada," IUI to lSE. increase is particularly marked after age 50, confirming an observation previously made, lo the effect that until recently lung cancer has probably been underdiagnosed in the older age groups in the general popu lation. To use these figures for purposes of comparison, it is necessary to combine the rates for certain age groups in order to conform to the age distributions used in this study. Since the exact populations in each age group for the years indicated is not known, this must be an approximation. However, the rates would be somewhat as follows Ape Group 20-1.% 45-54 6$ + Rate 5 -> 69 90-95 These rates are, ir. general, lower than those developed for the total f proved and suspected ) cases of lung cancer among the asbestos miners. The only large difference, however, is ir. the age group of 65 years and over, and it is quite possible that the raie for thi group may have increased for Canada between 1952 and 1954 as it did for the Province of Quebec ("Table 17). A further comparison has been made with an over-all rate obtained from the American Cancer Society for respiratory cancer deaths in Canada in 1953. This rate, for males, is 20.8 per 100,000, or 5 more per 100,000 than Phillips' 1950-1952 rate, and compares with 25.3 per 100,000 for proved cases and 33.8 per 100,000 for total cases among the 647 -v A. M. A. ARCHH ES OF INDUSTRIAL HEALTH Table 2! --.Vnmi><v of Deaths and Death Rates I'ti 100.000 by Age Groups for the Adult Male Population of the United States* Apt Oteup 30-44 46-M tt-r Total population 24.M4.O0O ft.0tt.UU) 6.340.000 5.670.000 4019.000 Cues *a 6,2M 6.4*3 16.600 JUit per 1 3.6 36.0 96.6 HU xt.i Dxl from "Vtul Stiltsito ol tb* t,'nud Stuu," Vpl, l tml 2, 1M2. asbestos miners in this study. It is there fore obvious that there are no important differences between the rates for asbestos miners and those for the general jxjpulation of Quebec and the Dominion of Canada. Since it is probable that figures for the United States are more complete and, there fore, possibly more comparable to the data for the miners, age-specific rates were com puted from "Vital Statistics of the United States," Volumes I and II, for 1952. These rates have been tabulated in Table 21, It is apparent that these rates compare favorably with those for the asbestos miners as shown in Table 8. Still other rates for the United States were obtained from the American Cancer Society, and for males, these were 25.3 per 100.000 in 1953, and 28.0 per 100,000 in 1955. They are not identical with the rate calculated from the figures of the office of Vital Statistics, but this is possibly because the American Can cer Society rates are for males of all ages. Nevertheless. the}', too. compare favorably with the rate- of 25 for 3-t for total cases) `'btamiucr amc.nc the asbestos miners. Turning tor a moment to a comparison between the asbestos miners and persons who are exposed to asbestos in one form nr another fas distinguished from the gen eral population groups just diseased, who have no exposure) an interesting observa tion can be developed by deduction. Hueper s* has stated that there are about 35,000 persons exposed in the United States, and we have found that the Canadian mines employ about 8000, Elsewhere, it has been estimated that the workers in England who have exposure total between 3000 and 5000. V'ith workers in Africa, Denmark, Nor 643 way, and other countries, at least 50,000 persons must be exposed throughout the world, and it can be assumed that this number has been fairly constant in the 20 years since 1935 when the first case of asbestosis with lung cancer was reported. At least 1,000,000 man-years of exposure has thus been accumulated, and this figure can be divided by the approximately 150 cases of lung cancer with asbestosis re ported during the 20-year period. This gives a rate of 15 per 100,000, which is at least indicative that any lung cancer rate which can be calculated for workers ex posed to asbestos dust is not much greater than that for the unexposed population. Com^ortjon Between Eight Counties Ad jacent to the Asbestos-Producing Areas and Eight Selected Counties.--To compare lung cancer mortality rates in the counties sur rounding the asbestos-producing areas with another group of counties in which no as bestos miners are likely to reside, the rates were computed on the basis of figures for the years 1950 through 1955. The eight counties selected for comparison were Argenteuil, Chateaugay. Montmagny, Portneuf, Richlieu, Riviere-du-Loup, St. Hyacinthe. and Terrebonne, mainly because they represent a wide geographic distribu tion throughout the Province. The counties selected because of their proximity to the asbestos mines include Arthabaska, Beauce. Drummond, Frontenac. Megantic. Rich mond. Sherbrooke and Wolfe Table 22 shows :h; number of lung cancer deaths for the years 1950 through 1955 for each of these counties, and a mortality rate, based on the adult male population in 1952. To emphasize the comparison, Megantic County has been shown separately, as has the Province of Quebec and also the Prov ince with the eight "asbestos-producing" counties subtracted. Because of its unique lung cancer death rate, Montreal et Isle de Jesus has also been listed in order to provide further comparison. It is apparent from the table that the lung cancer death rate for the eight counties Vol 17, June, JOSS A-e/^ / 2- o UWG CANCER IN ASBESTOS MINERS Table 22.--Number of Lung Cancer Death* and Rate per }00.000 Man-Yean Couatiti Mttiiaiic CounfT Elttn "Adjani" Counuts ElxBt Select*! Counu** Province ol Quefcec Province of Qua bee Ws ei(ht "Adjaaot" eaunuei Menmel el 1*1* de Jasui A dull Mite Mel* Lem* Cancer Deaths Population 1912 IM0 1951 1952 1953 19M 1935 13,100 92.600 93,000 Mtt.000 3 6 7 196 1 3 10 230 3 9 3 343 3 19 16 303 1 4 5 303 4 16 9 K? l.MOjDM JW.000 1 3 711 7 2M 1M 267 m 999 165 Ml 225 ' It Is UttUBtd that all male Ion* cancer deatbi odeurod after *f* . ToUl 15 49 1624 ia:o "0 SUie r*r 100.000 ia.9 9.4 ' 9.6 22.6 23,6 32.3 immediately surrounding the asbestos-pro ducing areas is practically identical with that of eight counties selected for comparison. While Megantic County has a rate nearly twice that of the combined eight selected counties, it is lower than the rate for the Province, and considerably lower than the rate for Montreal. The figure for Montreal would certainly be higher except for the very low numbers of deaths reported for 1950 and 1951, and it would appear that in those years some error in reporting has undoubtedly been made. On the basis of the other years, 1950 and 1951 deaths would be expected to be about 200 greater. This would result in a rate of 40 per 100,000. The on)}' possible conclusion from this comparison is that there is no evidence that the persons who live and work in the coun ties surrounding and adjacent to the as bestos-producing areas have any greater incidence of King cancer than those who live elsewhere in the Province. Comment on All Recorded Lung Cancer Cases, Living and Dead, among the Ashestos Miners.--Although a simple enumera tion or a!! 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 such cases for the record. There were nine deaths prior to the beginning of the time period covered by the study, including one in which the diagnosis was mediastinal lymphosar coma, During the period covered by this investigation, there were nine proved cases and three suspected cases in the cohort. Through 1956 and to date in 1957, there were eight deaths, six of which were merely suggestive of cancer of the lung and in cluded such diagnoses as mediastinal lymphosarcoma, mesothelioma, cancer of the leg with metastases to lung, abscess of lung, and cancer of the pancreas. One other was diagnosed on the basis of x-ray only. In addition, there are now living four cases in which the diagnostic evidence is strongly suggestive of lung cancer. This is a total of 33 cases of ail types, including 10 "sus pected" but unproved cases, and 4 that are still living. The remaining 19 constitute the total of proved cases of cancer of the lung among the asbestos miners since 1940. The proved cases averaged 59 years of age at death, and varied between 37 years and 68 years. Their working span covered periods varying from a minimum of 14 years to a maximum of 37 years. Only three men had less than 25 years of em ployment in the industry. Seven among those on whom such information is avail able had a weighted exposure placing them in Category III, and six worked in an exposure represented by Category I. There were only 17 among these prov ed lung cancer cases in which we have in formation regarding the presence of as bestosis. Asbestosis was present in nine, although it was minimal in two. Two path ologists disagreed regarding its presence in another. At least seven of the 19 proved lung cancers, therefore, were not accom panied by asbestosis. Summary and Conclusions Interest in the question of whether there may be an association between lung cancer Braun--Truan 649 / * rf*i- A. M. A ARCHIVES Of INDUSTRIAL HEALTH and exposure to asbestos Has been evident since the report in 1935 by Lynch and Smith of a case in which lung cancer and ashestosis were both present. As additional cases in which the two diseases coexisted were reported, a causal association appears to have been gradually accepted by many authors, although some workers considered the correlation to be inconclusive. The pres ent study was undertaken in an effort to de termine whether a causal relationship did, in fact, exist between exposure to asbestos and cancer of the lung. Since most earlier studies had been limited to enumerating the lung cancers found in certain selected samples, such as cases coming to autopsy or death certificates in which asbestosis was mentioned, it was apparent that they could not fulfill the re quirements of an epidemiological and sta tistical approach to the problem. The present study was, therefore, designed to meet the requirements of this method. After a preliminary survey to explore the availability of reliable information, data were gathered on workers in the asbestos , mines in Quebec, based on their medical records A cohort was defined as a group of asbestos miners having at least five years of exposure and who were in the industry in 1950. Data relative to their characteristics were collected and their status at the end of a -ix-yesr period of observation was de termined In the case of those who had died, an exhaustive search of death certif'ca`e; and insurance records was carried our in order to determine as nearly as possible the exact cause of death. Mortality rates from lung cancer for the general population of the Province of Quebec and its various counties and for the Dominion of Canada, as well as the United States were calculated from statistics collected in the appropriate places. Comparisons of the rates obtained for asbestos workers and for the other popu lation groups were made according to ac cepted statistical methods. Records were obtained on 6091 persons who fulfilled the criteria of the cohort. It was not possible to trace 133 of these for the whole period, but 5771 of the remaining 5958 were found to be still living in 1955 or later. Of the 187 known dead, cancer of the lung was considered to have been reasonably proved in 9 and to be strongly suggested in 3. The members of the cohort were studied with respect to age, length of employment, a weighted average of their exposure, and their smoking habits. It was found that 4673 were smokers within the definition of that term as used in this study. Thirty-four per cent of the cohort were more than 45 years of age, and thirty per cent had been employed for longer than 20 years. Thirty per cent had a weighted exposure which placed them in the category of highest ex posure. The mortality rate for lung cancer, as computed on the basis of nine "proved" deaths among the cohort was 25.3 per 100, 000. When the three "suspected" cases were added, the "total" rate for the cohort rose to 33.8. The importance of the suspected but unproved cases in determining these rates has been reiterated because it is iikely that such cases would not be included in the statistics for the general population and because they influence the results so mark edly. According to the findings in this study, the mortality rate from lung cancer does no: appear to increase with length of ex posure or with degree of exposure, a fact whiih yearns strong evidence against the carcinogenicity of asbestos Comparison of the experience among the asbestos miners with that of various seg ments of the unexposed, comparable popu lation shows that the observed number of deaths among the miners is not significantly greater than the expected number. The rate for proved cases among the asbestos miners (25.3 per 100,000) compares well with the rate of 22.5 per 100,000 for the rest of the Province, and 20.8 per 100,000 for adult males throughout the Dominion of Canada. It also compares satisfactorily with rates 650 Vol 17, June. }?Nt A-i/ il'XG CAXCER IX ASBESTOS MIXERS of 37.2, 25.3. and 28.0 obtained from various sources for adult males in the United S;ates. Finally, in this matter of comparison, it would appear that the world-wide experience 6. Behrens. W.: Experimental Asbestosis. Schweiz Zisciir. .-dig. Path 14:275-297, 1951. 7.i Behrens. W., Jr.: The Clinical Picture and Paiholiig.i of Asbestosis, Ztschr. Unfallmed u. Berufskrankh 45:129-140 (June 15) 1952. of persons exposed to asbestos dust is not 8. Berblinger, \V.: Increase of Lung Cancer worse with respect to lung cancer than that and Diseases Due to Dust Inhalation, Med. Klin. of the unexposed population. The counties surrounding the asbestos- producing areas, in which it is presumed most of the asbestos miners live, have al 27:1337-1342 (Sept. 11) 1931. 9. Berenblum. I.: Irritation and Carcinogenesis, Arch. Path. 38:233-244 (Oct.) 1944. 10. Bohne: Asbestosis, Deutsche med. Wchnschr. 62:928-930 (June 5) 1936. most identical mortality rates with those of 11. Bohme, A.: Results of Periodical Examina eight counties widely scattered through the tions of Workers in an Asbestos Factory, Beitr. Province, and are lower than those for the Silikose Forsch. 11 :34, 1951. remainder ol the Province, and much lower than the rate for Montreal. Since 1940 there have been 19 cases in which the diagnosis of primary cancer of the lung may be considered to have been 12. Bowles, O.: Asbestos-Milling, Marketing and Fabrication, Information Circular No. 6869, U. S Department of the Interior, Bureau of Mines, 1935, pp. 1-26. 13. Breslow. L.; Hoaglir., L.; Rasmussen, G., and Abrams. H. K.: Occupations and Cigarette proved. Approximately half of these cases Smoking as Factors in Lung Cancer. Am. 1. were associated with asbestosis. All but one Pub. Health. 44:171-181 (Feb.) 1954. ` died in the recognized "cancer-age" and at 14. Bristol, L. I.: Roentgenologic Aspects of least one-third had only the lightest ex Silicosis and Asbestosis, A. M. A. Arch. Indust. posure i Category 11 to asbestos dust, Health 11:189-195 (March) 1955. 15. Cancer of the Lung: An Evaluation of the i On the basis of what are believed to be Problem. Proceedings of the Scientific Section, complete and reliable data, it seems fair to Annual Meeting, American Cancer Society, !r.c.. conclude that the asbestos miners in the Nov. 3-4, 1953, Xev York, American Cancer Province of Quebec do not have a signif Society, Inc,, 1956 icantly higher death rate from lung cancer than do comparable segments of the general population. Furthermore, the death rate from lung cancer in the areas contiguous to the asbes tos operaiion? is comparable to that in areas widely scattered throughout the Province of 16. Cartier. P.: Asbestosis Cancer of the Lung, in discussion on Smith. W. E.: Survey of Some Current British and European Studies of Occupa tional Tumor, Problems. A, M. A Arch Indust. Hyg 5:262-263, 1952 17 Cartier. P.: Some Clinical Observations of Asbestosis in Mine and Mill Workers, A. M A. Arch. Indust. Health 11.204-207 (March) 1955. Quebec and is lower than in some urban ized area' within the Province. 18 Clerens. j : Research into Pulmonary Asbes tosis in Belgium. Arch beige' med Sociaie 557 565 < Soy 1 1951 REFERENCES 19 t':y;ie: ; and Lir:: M J 1:379, 1931. 1. Alascn- Escobar, R : Bronchial Carcinoma Review of 200 Cases, ,1. Internal Coll Surgeons 20 Conin. G. .1.: Duryee, H. C.: Maicr, H. C.; 26:375-379 fSept.) 1956. Pardee, H. E. E., and Wynter, E. L : The Effects 2. Allen, M. 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J Puli Health 4-4:1139-1166 (Sept.) 1954. 25. Davies, D. F.: Current Status of Lung Cancer Research: Some Pathogenetic Aspects, CA 6:169-174 (Sept.) 1956. 26. Desmeules. R.; Rousseau, L.; Giroux, M., and SiTois, A. : Asbestosis and Pulmonary Cancer, Semaine de. hop. Paris 25:1820-1823 (Aug. 7) 1947. 27. Doll, R.: Bronchial Carcinoma: Incidence and Aetiology (Milroy Lectures, abridged), Brit. M. J. 2:521-527 (Sept. 5); 585-590 (Sept. 12) 1952. 28. Doll. R.: -Mortality from Lung Cancer Among Asbestos Workers, Bril. J, Indust. Med. 12.81-86, 1955. 29. Donnelly, J.: Pulmonary Asbestosis, Am. J. Pub. Health 23:1275-1281 (Dec.) 1933. 30. Dorn, H. F., and Culler, S. J.: Morbidity from Cancer in the United States, Pub. Health Monograph No. 29, P. H. S. Publication No, 418, U. S. Public Health Service, 1955, 121 pp. 31. Dorn, H. F.: Cancer Morbidity Surveys: A 'fool for Testing Theories o Cancer Etiology, Am. J. Pub. Health 45:615-621 (May) 1955. 32. Egbert, D. S., and Geiger, A. J.: Pulmonary Asbestosis and Carcinoma: Report of a Case vrith Necropsy Findings, Am. Res1. Tuberi 34:143-150 (July) 1936. . 33. Ellman, P.: Pulmonary Asbestosis: Its Clinical, Radiological, and Pathological Features and Associated Risk of Tuberculosis Infection, J. Indust. Hyg. 15:165-183 (July) 1933. 34 Ellman, P.: Pulmonary Asbestosis, Proc Roy Soc Med. 34:S57 (July) 1941. 35. Feil. A. Pneumoconiosis in Asbestos Workers, Presse med. 39:1872-1874 (Dec. 19) 1931. 36. Fulton. W B.; Dooley, A.; Matthews, J. L., and Hourz, R. L.: Asbestosis: Part III. The Effects of Exposure to Dust Encountered in Asbestos Fabricating Plants on the Health of a Group of Workers, Special Bulletin No. 42, Pennsylvania Department of Labor and Industry. Bureau oi Indus:. Standards. Sept. 20, 1935 37 Gardner, L U., and Cummings, D. E.: Studies on Experimental Pneumoconiosis: Inhala tion of Asbestos Dust; Its Effect upon Primary Tuberculous Infection, J. Indust. Hyg. 13:65-81 (Feb) ; 97 (March) 1931. 38. Gilliam. A. G.: Mortality Trends in Lung Cancer, Cancer 8:1130-1136 (Nov.-Dee.) 1955. 39. Gilliam, A. G.: Mortality Attributed to Lung Cancer in the Large Cities of the United States in 1948 and 1949, J. Nat. Cancer Inst. 15:1307-1312, 1955. 40. Gloyne, S- R-: Two Cases of Squamous Carcinoma of the Lung Occurring in Asbestosis, Tubercle 17:5-10 (Oct.) 1935. 652 4|- Gloyne, S R_: Pneumoconiosis : A Histo logical Survey oi Necropsy Material in 1205 Cases, Lancet 1:810-814 (April 14) 1951. 42. Gloyne, S. R_: A Case of Oat-Cell Car cinoma of the Lung Occurring in Asbestosis Tubercle 18:100-101 (Dec.) 1936. 43. Gloyne, S. R., and Merewether, E R- A.: Asbestos, Occupation and Health, Supplement to Encyclopedia on Occupation and Health, Geneva, International Labor Office, 1938, 44. Goldblatt, M. W., and Goldblatt, J,: In dustrial Carcinogenesis and Toxicology, in In dustrial Medicine and Hygiene, edited by E. R. A Merewether, London, Loudon, Butterworth & Co., Ltd., 1956, Vol. 3, pp. 185-188. 45. Haenszel, W. M-: Epidemiological Tests of Theories on Lung Cancer Etiology, Pub. Health Rep. 71:163-172 (Feb,) 1956. 46. Hammond, E. C.: Lung Cancer and Com mon Inhalants, Cancer 7:1100-1108 (Nov.) 1954. 47. Hammond, E. C,: Etiology of Bronchiogenic Carcinoma, CA 6:156-168 (Sept.) 1956. 48. Holleb, H. B.( and Angrist, A.: Bronchiogenic Carcinoma in Association with Pulmonary Asbestosis: Report of 2 Cases, Am. J. Path. 18: 123-135 (Jan.) 1942 49. Homburger, F.: The Co-Incidence of Primary' Carcinoma of Lungs and Pulmonary Asbestosis: Analysis of Literature and Report of 2 Cases, Am. J. Path. 19:797-807 (Sept.) 1943. 50. Horn, D.: Is Lung Cancer on the Increase? Evaluation of Present Day Evidence: Cancer of the Lung, Proceedings of the Scientific Section, Annual Meeting, American Cancer Society, Inc, Nov. 3-4, 1953. 51. Homig. F.: Clinical Considerations on the Question of Industrial Cancer of Asbestos Work ers, Etschr Krebsforsch 47,281-287, 1938. 52. Hueper. W. C. Cancer in Its Relation to Occupation and Environment, Bull. Am Soc Control Cancer 25:63-69 (June) 1943. 53. Hueper, W. C.: Significance of Industrial Cancer in the Problem o: Cancer. Occup. Med. 2.190-200 lSept) 194/, 54 Hueper. W. C : Environmental and Occupa tional Cancer, Public Health Service Supp. 209, U. S. Public Health Service. 1949. 55. Hueper, W. C.: A Methodology for Environ mental and Occupational Cancer Surveys, Public Health Monograph No. 1, P. H. S. Publication No. 12, U. S. Public Health Service, 1950. 56. Hueper, W. C.: Environmental Lung Cancer, Indust. Med. 20:49-62 (Feb.) 1951. 57. Hueper, W. C.: Occupational and Environ mental Pulmonary Cancers with Special Reference to Pneumoconiosis, Proceedings, 7th Saranac Symposium on Pneumoconiosis. 1952. 58. Hueper, W. C.: A Quest into the Environ mental Causes of Cancer of the Lung, Pub. Vet. 17. hm*. 195 /*<*/ ^o LL'SG CANCER IN ASBESTOS MINERS Health Monograph No. 36, P. H. S. Publication No. 452, U. S. Public Health Service, 1955. 59. Hueper. W. C.: Environmental Causes of Cancer of the Lung other than Tobacco Smoke, Dis. Chest 30:141-158 (Aug.) 1956. 60. Isselbacher, K. J.; Klaus, H., and Hardy, H. L.: Asbestosis and Bronchogenic Carcinoma: Report of One Autopsied Case and Review of Available Literature, Am. J. Med. 15:721-732 (Nov.) 1953. 61. Kehnaway, E. L-, and Kennaway, N, M.: A Study of the Incidence of Cancer of the Lung and Larynx, J. Hyg. 36:236-267 (June) 1936. 62. Kennaway, E. L., and Kennaway, N. M-: Studies of Incidence of Cancer of the Lung and Larynx, Brit- J. Cancer 5:153-158 (June) 1951. 63. Kiotz, M. O.: Association of Silicosis and Carcinoma of the Lung, Am. J. Cancer 35 :38-49 (Jan.) 1939. 64. Lanza, A. J.; McConnell, W. J., and Fehnei, J. W.: The Effects of the Inhalation of Asbestos Dust on ihe Lungs of Asbestos Workers: Pre liminary Study. Pub. Health Rep. 50:1-12 (Jan. 4) 1935. 65. Lanza, A. J., editor: Silicosis and Asbestosis, New York and London, Oxford University Press, 1938. 66. Lew, E. A.: Use of Life Insurance Com pany Records for Cancer Studies, A. M. A. Arch. ,, Indust, Hyg. 5:198-203 (March) 1952. 67 Linzbach, A. J.. and Wedler, H. W.; Occu pational Cancer among Asbestos Workers, Arch, path. Anat. 307:387-409, 1941. 75. Merewether, E. R. A.. Annual Reports of 'the Chief Inspector of Factories, London, His Majesty's Stationery Office, 1947. 76. Merewether, E. R. A., editor: industrial Medicine and Hygiene, London, Butte*worth & Co.. Ltd., 1956, Voi. 3. 77. Nordmann, M.: The Industrial Cancer of Workers in Asbestos. Ztschr. Krebsforch. 47 ;288302, 1938. 78. Nordmann, M., and Sorge, A.: Pulmonary Cancer Produced by Asbestos Dust in Experi mental Animals, Ztschr. Krebsforch. 51 -.168-182, 1941. 79. Phillips, A. J.: Mortality from Cancer of the Lung in Canada (1931-1952), Canad. M. A. J. 71:242-244 (Sept.) 1954. 80. Saupe, E.: Further Contributions to the Roentgenological Diagnosis of Asbestosis, Arch. Gewerbepath. u. Gewerbehyg. 9:391-406, 1939. 81. Smith, K. W.: Pulmonary Disability in Asbestos Workers, A. M. A. Arch. Indust. Health 12:198-203 (Aug) 1955. 82. Smith, L. W.: Pneumoconiosis and Lung CanceT with Special Reference to Silicosis and Asbestosis, Compens. Med 2:3-10 (Nov.) 1949. 83. Smith, W. E.: Survey of Some Current British and European Studies of Occupational Tumor Problems: Part III. Asbestos, A. M. A. Arch. IttdusL Hyg. 5:242-263 (March) 1952. 84. Stoll, R.; Bass, R, and Angrist, A.: Asbestosis Associated withBronchogenic Car cinoma, A. M. A Arch. Int. Med. 88:831-834 (Dec.) 1951. 68. Lynch, K. M., and Smith, W. A.: Pul monary Asbestosis: Carcinoma of Lung in Asbesto-Silicosis, Am. J. Cancer 24 56-64 (May) '.955 69. Lynch, K. M., and Smith, W. A.: Pul monary Asbestosis: A Report of Bronchial Car cinoma and Epithelial Metaplasia. Am. J Cancer 36:567-573 (Aug.) 1939 70 Lynch, K M,, and Cannon, W. M.: Asbest-njis Analysis o: 40 Necropsied Cases, Dts. Chest ; a : 74. j ; N ov - Dee.) 1946. 7! Mcr'heeters, S. B.: A Survey of a Group of Employees Exposed to Asbestos Dust, j. Indus:. Hyg. 18.229-239 (April) 1936. " 72. Merewether, E. R. A.: The Occurrence of Pulmonary Fibrosis and Other Pulmonary Affec tions in Asbestos Workers, J. Indust. Hyg. 12: 198 (May); 239 (June) 1930. 73. Merewether, E. R- A., and Price, C. W.: Report on Effects of Asbestos Dust on the Lungs and Dust Suppression in the Asbestos Industry, London, His Majesty's Stationery Office, 1930. 74. Merewether, E. R. A.: A Memorandum on Asbestosis. Tubercle 15:109; (Dec.) 1933; 15: 152 (Jan.) 1934. 85. Teleky, L.: Occupational Lung Cancer, Acta Union internal, centre Cancer 3:253-273, 1938; also, Zentraibl. Gewerbehyg. 27:33, 1940 86 Vorwald, A. J.; Durkan. T. M., and Pratt, P. C.: Experimental Studies of Asbestosis, A. M. A Arch. Indust Hyg. 3:1-43 (Jan.) 1951. 87. Wedler, H- W.: Asbestosis and Lung Cancer, Deutsche med Wchnschr. 69:575-576 (Aug. 6) 1943. 88. VVegelius. C. Changes in the Lungs in 126 Cases of Asbestosis Observed in Finland. Acta radio! 28:139-152, 1947. 89 W'erber, M.; Pulmonary Asbestosis Asso ciated with Carcinoma, Zentraibl. Arbeitsmed. u. Arbeitsschutz 2:179-180 (Nov.) 1952. 90. Wood, W. B., and Gloyne, S. R.: Pulmonary Asbestosis Complicated by Pulmonary Tubercu losis, Lancet 2:954-956 (Oct. 31) 1931. 91. Wyers, H.: Asbestosis, Postgrad. Med. 25: 631-638 (Dee.) 19*9. 92. Wynder, E, L,, and Graham. E. A.: Eliolugie Factors in Brcmdiiogenic Carcinoma with Special Reference to Industrial Exposures; Report of 857 Proved Cases, A. M, A. Ardi. Indust Hyg 4:221-235 (Sept.) 1951. Broun--Tnan Primit4 m/ m tfu Unittd StMtt Amfic* 653 I 1 J J 3 V e 36. !I ` Oat further Interesting observation from Tsble Ix'le the r:;!::r | marked Increase la die total number of cate* for the Province between i960 end 1955. It U assumed that at leaet part ot thle increase It due to 1m- proved recognition and reporting of lung cancer during the interval. For thl* reteon, the year* 1954 and 1955 were thought to bo more nearly repre> ' tentative of actual condition*. Even'eo, U l* quit* likely that the geaor&l population 1* not etudled for lung cancer with the *ame diligence with which tbit disease le looked for In the miser*, and It soots* probable that the mor- tallty rate* for the Province may be low. Tbla would appear to be substan tiated by the fact that the reporting of case* In the cohort showed no such laer*a*e over the eame period. - '' f'j 7 '' > Table Iowa* compiled to ebow tho annual ag*-*poclflc lung cancer H rate of caeeo la which the death certificate merely read "cancer of the lung", a* distinguished from those In which tho diagsoole was confirmed by autopsy, *V , . e surgery, or biopsy. The term "specified primary" rotor* to those case* In ' . *, . '. * * _ ` . these two categorise la which the tumor woe specified as having originated la the lung. It will be noted that, of tho total cases reported lo 1955, a much higher percentage than In 1954 were specified as primary. The table alee the** that a higher percentage of tho total cases certified la 1955 were proved, gain Indicating Increasing Interest la this disease, - 0286 L u a C * a c r D e a ih fl fo r th * P ro v in c e o f Q uebec| (D *U from D ciiK C e rtifica te *) 5; -i twsj pif*l /^ V) & f* -* ^ v> -* ^ r*n* -- ^ t^A in Vmim^ a4* C-- - -rt^2 O* U - o P-<w v ^*t *la --4 "I i o n a* n| cr * ^ l -- -- o > .Ve A2 o s 1* o b2 -a*A* O Vcvb QEo V* --* _ ** --* > aw *"v c* r i* * u s 1 I? qJ U 0* %* a e m, **t WHLnj o -- n o * * o o oo o o r* e <* ^ w^i ^ * 2c * n *vi m*r *c r L5o*. *g* M"o>. 4G&w * oc 5 I eV S0 Mi oe o is o " * la *, a o *" * e 2H Z ao. U* 3J T >!, If k i |w 'il a,* iji A *! ssi^ | J -- V *4 r p ** i ^4 ^ 2 H e* oU * t & tof 3 > o f u 21 *2] 5 u 1 *< * ift j^ 4 -3 a * 5 c .< r u u N N 6 ** P* W p- ^ 2J.> 4.7 O v*r-U V^^ o n ne Zn1 o^ 02S7 -1 7 ' \ \ \ " 7r m'T*-- I: * A comparison has boon nude between the ago-opeeUie rates iaoa tl f la T*bl IS, ud too** for the cohort, shown la Table y. Aa average of the 1914 tad 1955 rate* ter the Prevlace haa beta used, alaca the 1955 figure me* hljhar end may bava baaa exceptional, l* Thla comparison, summarised la Table ehowa that tba ebaerved dumber at daatha la oar cample la not significantly greater than the expected number of daatha, baaed oa the average of the 1954 aad 1955 figure# for the province. It (a true that, la the caaa of the ago group of 65 aad over, the f|*a daatha provide a figure which la aimoat aigalflcaat at the 957, level. However, It ahould be noted that thla number Include# oae of the ouopected bet unproved caae* prevloualy referred to. Furthermore. U to rather likely that the rata for the gaaeral population la uaderetated la thie age group, for the ebvieuo reaaoa that the exact cauao of death la the very old la not o matter if the came Intensity of Interest as It is la younger poreoas. . TABLE IS Ago Oreup Comparison of the Actual and Expected Humber of Lurn Cancer Deaths by Arc Amen* Asbestos Miners Province Expected'*1 Observed No, Total Specified Primary Rate per 100. 000 No. of - - I No. Of Minora Death a of Dontha Proved l utal >14 45*54 55.64 65# Unknown 1.8 24. 5 67.6 89.3 -- 3901 1124 615 . 315 3 0* 2 2 - 2 m .. ... 11 1. 3 33 45 00 e Actually .4 o The expected number te based on the average of the 1954 aad 1955 o|tepeclftc rate# for the Province of Quebec._____________________ 02SS . 39. V Table also answers a question previously raised. It ih^vi that "` tie member* of the cohort hove cot died Irom lung cancor at an ag earlier * thee the general population, and that such an explanation cannot be offered 1 v for tie absence of lung cancer In 240 men with more than 40 year* of *m ploymout reforred to on page 24. ' Before leaving tile comparison of the province with the minere. it should be shown that their age distributions are reasonably the same. That t I this te the cnee can be obeerved from the following tabulation: 7'ACLZ' /? . Age Distribution of Adult Melee for the Province of.Quebec, 1951 (Rapport, 1954) AS* _ Grevf Province Humber Poi-ccstaqe 20*44 45-54 55*64 65 fetal 727, 135 108,952 128,944 113,467 1, 158,498 63 16 11 10 Too Percenter* In Cohort A- 46 19 10 5 100 It ehould ho remembered that the minere retire and consequently, |l can be expected that the oldeet age group will be larger la the general popu- r* Istlee, The data presented In Table yf indicate# that the lung cancer rate 1 't gsesrslty decreases after age TO. Thrrefora, we could expect the rate for ! all people over 65 to be emallcr than the rate for the group between 65 and 75, 4 V vMcb would apply to the oldeet group of minere. It ie felt thet by using the hole adult n-.alo population, we have developed rates for the general popu* 40 laticu wfclai ars suasrbst lew?* taaa li wo Led bora si u* iw e'cLO* tfc po^pla la tta c=s?3l pwpclzitaa over 75. A coaapsrlssa beSseca Uo arbertoa caber* ud U*i populates d Ua Derbies aa avbab v&s siedo, uic; O etntbiUal osLerbl jo n Iron ssrcral oerce3(*sa caa ecjrte, Ptillipa (77) gats *g* - avx - specific rsice fer Caar.da lor urea perjuis bettrosa 1*51 sad 1555. Halos tar aalas or elves Is Tcblo $. >1 +*x yV JxtfAiSfji+S ' **, **r **"*?&&if*' ^'7--- V_____ ^ r AgtOros? trader 30 30-34 <2t 40-54 45-49 80-34 05-53 60-C4 98-03 70-74 73-79 90-04 95 plaa All cjjoa //: IKI-1933 0.3 0.9 .. ' 2.0 5.9 5J W ' 12.7 13.3 . i3a 10.7 15.0 04 11.4 . 2.9 Grwr* etf } ears_____ _ 1311-P42 0.3 0.9 r. '/ 5.3 6.4 124 10.9 ' 7 37.0 85.7 94.3 . 50.3 50.0 27.0 14.3 7.1 tfEO-l.'Si L0 O.S 3.8 0.3 10.7 / 7 37.2 83.7 77.3 102.9 36.3 ^ 03,9 / 89.7 71,0 13. S Z* Mortality Iras bs^ ccecct b Csuficb '1521 to 1952^. 02SO / \ u. These Xlgurs* show strikingly the Increase In rtlti be tweea 1 <531 tab 1952, sad this increase Is particularly marked after age 50, confirm* lag an observation previously mads, to the effect that until reeeutly lung cancer has probably beea uatUr-dlagaoeed In the older age groups la the general population. To use these figures for purposes of comparison. It Is necessary / It combine the rates for esrtaln ago groups la ordor to conform to the sge Ustrlbutleas used la this study. Sines tht enact populations In sach ags group 1st the years Indicated Is not known, this mutt be an approximation. However, As raise would bo somewbtt as follows! Afto Group 20.44 45-54 55.44 45 o Kate 22 49 90-95 These rates are, lafgonorml, lower than those developed for the total (proved and suspected) cases of lung cancer among the asbestos minors, lbs only Urge difference, however. Is la the age group of 4$ years tod over, tad It Is quite possible that the rate for this group may have Increased for Canada batweea 1952 and 1954 as It did for the Province ef Quebec. (Sec fable >40/7' V 0291 / Chi 12. A further comparison hit been made with *n over .all rate obtained from the American Cinder Society lor respiratory cancer deaths In Canada n la 19)3. Tht* rata, tor male*. U 20.8 par 100,000. live more per 100,000 that Phillip*1 19)0*1952 rata, and compare* with 25.3 par 100, 000 tor proved ease* tad 33.8 par 100, 000 tar total caaaa among the asbestos miner* In tht* study, It U therefor* obvious that there are no Important difference* between lb* rata* (er aabaetoa mtaere and thoee for the general population of Quebec *ad the Dominion of Canada. . Since It to probable that figure* for tb* United State* are more templet* and. therefor*, possibly more comparable to the data for the miner*. *l.*p*cUU roue were computed from "Vital Statistics of the United States", 'H' Velum** 1 and 11, for 1952. These rate* have been tabulated in Table id, . .. JJ ... TASDS )4 Number of Death* and Doath Rates par 100,000 by A|* Croup* for tb* Adult Mai* Population of the United State**--Data From "Vital Statistic* bi the United States", Volnme* 1 and 11, 1952 \ i\ 1 1 A^e Croup 10.44 45.54 *3-4* 43 rt*i Population 24, 544, 000 8,005,000 8,340,000 5.610,000 44, 619. 000 Case* 883 2919 6254 6483 16, 599 Rat* per 3.6 36,9 98.6 1M, 3 37,2 0292 t I s i l It 1* apparent that the** rate* enmpsre favorably with :ho^ fer ifc* itbesto* miner* a* shewn In Table V. Still oth*r<r*t*i (or the United i 1. Itt* were obtained Iron*. the Americas Cancer Society, and lor male*, the** were 15. 3 per 100, 000 la 1955, and 26, 0 per 100.000 In 1955. They 3 are set Identical with the rate calculated lrotn the figure* of the office of Vital Stailetice, but thl* la poeatbly because the Amertcaa Cancer Society J rates are for males of all age*. Nevertheless, they, too, compars favor* c ably with the rates of 25 (or 34 for total cases) obtaining among the asbestos miner*. 0 a Turning lor a moment to a comparison between the asbestos miner* . asd persons wbe are exposed to asbestos in one form or soother (as die* lUgslshed from the general population groups Just discussed, who have no t eipeeure} an Interesting observation can be developed by deduction. Hueper - has stated that there are shout 35, 000 persona exposed In the United States, ;1 tad we have found (bat the Canadian mine* employ about 6,00. 0. Elsewhere, 1 U gas been estimated that the worker* In England who have exposure total between 3,000 and 5, 000, With worker* In Africa, Denmark, Norway, and " sthsr countries, ml least 50, 000 peraons must be exposed throughout the world, ted it can be assumed that this aumher ha* been fairly constant la tbs 20 years ttsc* 1935 when the first case of aabeetoala with lung cancer was reported. At least a million man*yeare of exposure ha* thus been accumulated, and thitflg4** aha bo divided by tho approximately 150 cases of lung cancer with ittsitetii reported during the 20*ysar period. This give* a rat* of 15 per i;0,000 which U at least Indicative that any lung cancer rate which can be eiieulated fur corner* cvposerf to asbestos dust i* r.s: rruefc that for the unexpossd population. thsa , Comparison Betwocn Eight Counties AdjscttU to the As bcetoe-Producing Aren* Old rirht Selected Counties To coatpo.ro lung cancer mortality rate* In the counties surroundln| the asbestos-producing Arena with another (roup of countiaa la which se iibestoi cv,laere at* likely to reside, the rate* wore computed on the kttla of flgurs* for the year* 1950 through 1955. The eight countie selected far comparison were Mrgenteuil, Chatoaugay, Montmagny, Portae uf, gtchlieu, Rlvlero-du-Leup, St. Hyacistho, end Terrebonne, mainly because they represent a wine geographic distribution, throughout the Province. The teuailes selected because of their proximity to the asbestos mine* Include Atthahaeka, Beaueo, Drummond. Troatenac, Megantlc, Richmond, Sherbrooke, sad hrolfe. Table )4 shows the autnbir of luag caacor deaths for the years 1950 through 1955 for each of those counties, aad a mortality rate, based on the sdult male population la 1952, To emphasita the comparison, Me gentle County has been shown separately, ae has the Province of Cuahec aad alao the Province with the eight "asbesUis-produclng" counties subtracted, Because of its unique lueg cancer death rate, Montreal et Isle do Joeus bae also been listed la order to provide further comparison. 0294 45 0295 M ontreal <t Ilc de Jeaua 194,000 1 T ( 158 192 185 225 T70 I: Is apparent (rem the table that the lung cancer death rate far the eight esaatiea Immediately surrounding the aebestot-producmj area* U practlcally-ldentlcal with that of eight counties selected lor comparison. Vrhll# Megantlc County ha* a rat* nearly twice that of th* combined eight tclected eouatlea. It ( lower than the rate for the Province, and cenaiderably lower than the rate for Montreal. The figure for Montreal would certainly be higher except for the vory low number* of death* reported for 1950 and 1951. and it would appear that in those yeare some error in repotting has . undoubtedly been made. On the htal* of th* other years, 1950 and 1951 death* would be expected to be about 00 greater. This would result in a rate of 40 per 100.000. ... . The only poeelble conclusion from this comparison l* that thero la no evidence that the persona who live and work in the counties surrounding and adjacent to the asbestos-producing area* have any greater incidence of lung cancer than those who live elsewhere U the Province. . . Dlocuasien-of All Recorded Lung Cancer Cnees, Living and Dead. f.~ffTon*??the Asbeetoe Miners Although a simple enumeration of all the known or suspected case* id cancer of the lung in these nreae has no particular value from a statistical point of view, U l* of Interest to summarise such case# for the roeord. There were nine death* prior to the beginning of th* time period covered by the Study, including one tn which the diagnosis wne mediastinal lymphosarcoma. L 47. Our Is; the period covered by this Investigation, there were nine prove! cnoi and three suspected cases in the cohort. Through 1956 end to date in 1957, there were eight deaths, el* of which were merely suggesttve of cancer of the lung end included euch diegsoeee ee mediastinal lymphosarcoma, sttio. the Home, cancer of the leg with metastasot to lung, ebeeee of lung, end cancer of the pancreas. One other wee dUgnoeed.on the beeie of x-ray only, la addition, there ere bow Uvlng four, caaet la which the diagnostic evidence ta strongly suggestive of luag caaeer. This lo e total of 55 cates of all types, Including ten "suspected" but uaproved cases, and four that ars still living. The remaialag 19 constitute the total of proved caaea of cancor of the lung among tho asbestos miners sines 1940. Ths provsd cates averaged 59 years of age at death, and varied between 57 years and 58 year*. Their working epan covered period* vary* lag from a minimum of 14 years to a maximum of 57 yaars. Only three men had late than 25 year* of employment la tha Industry, Sevan among those on whom euch Information Is available had a walghted exposure placing them in category 111, and tin worked In an enpoeur* represented by entogory 1. There wore only 17 tmeeg these proved lung esnear case* in which we have icformailco regarding the presence of asbeetoei*. Aebeetosi* was present in nine, although it was minimal ta two. Two pathologists disagreed regarding Us presence la another. At least seven of the 19 proved lung cancers, therefore, were not accompanied by asbestoels. 0297 48. Summary onrt Caa:i'..ilc:ii Interest la she question of whether there msy be an association between lung cancer and exposure to asbestos bet been evident since the report la 141$ by Lynch and Smith of * cnee la which lung cancer and tehee* toele were both present. As additional caeca la which the two diseases co- ealeted were reported, a causal association appears to have been gradually accepted by many authors, although some workers considered the correlation to be inconclusive. The present study was commissioned la an effort to determine whether-a causal relationship did, la fact, exist between exposure to asbestos and cancer of the lung. Since most oarller studies had been limited to enumerating the lung cancere found In certain selected samples, such as cases coming to autopsy or death carttflcatee In which aebeetesle was mentioned, It was apparent that thay could not fulfill the requirements of an epidemiological and statistical approach to the problem. The present study was, therefore, designed to meet the requirements of this method. After a preliminary survey te explore the availability of reliable Information, data were gathered on workers In the eebestos mines In Cuebec, . /f s yt $**+< /* based ea their medical records. A cohort was defined aconsnjlL << < suortiLit 1 ^,yutr //av,vc y*r- /XVve /Wxr /" crtmanaSoltiMrkgrnoSo-t-M^*-----' . , --,..j *--*-- 4>*e */a<t rsa ,/vovr/v^K tfi~ - fiats rslatlve to their characteristics were collected and their statue at tha and of a a lx* year-period of observation was determined. In the case of those who had died, an exhaustive search of death certificates and insurance records 0295 19. V4l carried out io order to determine *s nearly at possible (be exact ciuie of death. Mortality rotes from lung cancor for the general population of the Province of Quebec end Us various counties nod for the Domioloa of Canada, os wo 11 the United States were calculated from statistics collected In the Appropriate places, Comparisons of the rate* obtained for aebettos workers and for the other population group# wore made according to accopted etatletlcal V<n (- . *--M ' Records were obtained on 6091 persons who fulfilled the criteria of the cohort. It *ti not possible to trace 133 of these for the whole period, bat 5991 af the remaining 5956 wars found to bo sttll living in 1955 or Inter. Of the 169 known dead, cancer of the lung was considered to have been roaeon- ably proved In nine and to be strongly suggested la three. ' The members of the cohort wers studied with respoet to age, length of employment, a weighted average of their exposure, and their smoking habits. Jour thousand, six hundred and eovanty-three were found to be smoker# within the definition of thst term as used In this study." Thirty-four per ,cent Sa1 - 4 -' of the cohort were more than 45 years of age, and 3071 had bsen smptoyed for longer than 20 years. Thirty per cent had a weighted exposure which placed them la category of highest exposure. The mortality rats for lung cancer, ea computed on the basis of nine "proved** deaths among the cohort was 25.3 per 100,000. When the three "tuspected*' cases were added, the "total" rate for the cohort roses# 33.8. o?ss 50. Tb# ImjKftiaet el the suepectod but unproved case* la determining that* rate* ha* beta reiterated because it is likely that such cases would not bo Included Is the statistics for tbs general population and because they Influents lbs results so markedly. According to tbs findings lb this, study, tbs mortality rats from lung cancer dess net appear to increase with length of exposure or with degree of exposure, a fact.which presents strong ovldeace against the carcinogenicity of asbestos. Comparison of tbs oxperla&ce among the asbestos miners with that of various segments of tbs uaexpeaed, comparable population shows that the observed number of death* among tbs miner* Is not significantly grsatar than the expected number. The rat* for provod cases among the aebsetc* minors (25.1 psr 109,000) compares well with the rate of 22.5 per 100,000 ' for tb* rest of the Province, and 20.8 par 100, 000 for adult mala* throughout the Dominion of Canada. It alto compare* satisfactorily with rate* of 51.2, 25.0, and 21.0 obtained from various source* for adult male* in tb* United States. Finally, la tht* matter of comparison, It would appear that tb* world* wide experience of person* exposed to asbestos dust is not worse with respect to lung cancer than that of tb* unexposed population. The countlv* surrounding the asbestos-producing are**, and In which It la presumed most of the asbestos miners Uv, have almost Identical mor tality rate* with tboaa of alght counties widely scattered through the Province, and are lower than (boss for the remainder of the Province, and much lower then tb* rate for Montreal. or? si. Since 1940, there have been 19 cases la which the diagnosis of primary cancer of the lung may be considered to have been proved. Approxi mately half of theec caaea were aaaoclated with aabeetoala. All but on* diet Is the recognised eanc* -aje" and at least one-third had only the lightest exposure (category I) to asbestos dust. . On the basis of what are belltved to be complete and reliable data. It aeeme fair to conclude that the aebestos miners In ths Province of Quebec do not have a significantly higher death rate from lung cancer than do com parable segments of ths gsneral population. ' Furthermore, the death rate from dung cancer la the areas contigu ous to the asbestoe operations Is comparable to that In areae widely ecattered throughout the Province of Quebec and te lower than In eome urbanised areas ' within the Province. 0301 fcihllorrap jy 1. Ala*clo, Zecobar A. Bronchial carcinoma; review of two hundred caee*. 3, Internet. Coll, Surgeon*. 26: 375-379, September, 1956 2. Allen, M. L. Broncbiogcnic carcinoma asaoclated with pneumono- corueeiei report of two caaee, J. Induet. Hyg. 16: 346-347, November, 1934. _ 3. American Cancer Society, lac. Cancer of the lung; an evaluation of tbe problem. Proceeding* of the Scientific Section, Annual Mooting, Nov. 3-4, 1553. American Cancer Society, Inc. Now York, 1956, 322 pp. 4. Andcraon, C. S, and Dlble, 3. H. 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