Document rZ15mrvOn2EqZ3jpw6p2RZOE

Reprinted Ifom the A. M. A. Archives of Industrial Health June 1958, Vol. 17, pp. 634-653 Copyright 1958, by American Medical Association FROM An Epidemiological Study of HYGT FomATm mU Fllth *. Pittsburgh 13. p3 Lung Cancer in Asbestos Miners DANIII C. AUN, M.O., T. DAVID TKUAN, M.A* Ptmbvrth 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 emphasise the percentage relationship in extremely small series of <ases, 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 came a specific type of pneu moconiosis, and because persons who show this form of pneumoconiosis often come to autopsy and provide a ready source of material for study. It was in this way that reports of the simultaneous occurrence of lung cancer and asbestosis began to accu mulate after the rejort 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 the Quebec Asbestos Mining Association. Medical Director (Dr. Braun) and Statistical Consultant (Mr. Truan), Industrial Hygiene Foundation. 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 Hueper M 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 \l/i 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 Angrist49 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 radiological!)' diagnosed cases of asbestosis among 476 workers in Finland, and found no cases of lung cancer in this group. Goldblart and Goldbiatt 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 634 ' /r/d o "//>/& !.C\G CANCER JN ASBESTOS MIXERS is no reliable criterion by which one cau .utiioiMtc carcinogenicity and. as is well known, relatively minute changes in the structure of a chemical carcinogen axe suffi cient to diminish or eliminate carcinogenic "schedules!" area*, by which is meant, "thoy? areas where processes are carried on which were scheduled under the Asbestos Industry Regulations of 1931 as being dusty." action. There is, furthermore, a complete lack If asbestos is indeed to be regarded as a of definition of terms as used in the pub carcinogen, the need is felt to demonstrate lished literature. For example, the term some property which can be regarded as "asbestosis," as used, may refer to changes something more than inertness." observable only by microscopic examination These authors advance the theory that, of the lung tissue, or it may mean a radiountil some more experimental evidence of logically detectable condition. direct carcinogenesis by asbestos or a de- Most of the published reports obviously comjosilion product of it can be obtained, included women among their cases, but asbestos might be considered as a "co-car some of them do not give the number or cinogen" which only induces a further de projxirtion of women involved in the study. velopment of a preneoplastic condition There is also a lack of uniformity as to brought about by something independent of what type of exposure most studies have the asbestos, such as an endogenous factor. dealt with. Of 99 cases enumerated by Thus the literature, while tending to sup Hueper** in 1955, only 10 apfiear to have port the thesis that asbestosis is in some way related to the development of lung cancer, is by no means unanimous. Alto originated in the United States, and 7 in Canada. Some of the earlier reports ap parently included asbestos miners, but it gether, it is perhaps more confusing than can be assumed, since 82 of the 99 cases 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, 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. and most of the authors do not make claim Such factors as smoking habits, family to having done so. What has happened is history of cancer, length of time in the that succeeding authors have drawn conclu industry, and age of the individual case are sions and generalized beyond the scojw of also notably absent in the majority of these the works which they quote. Nowhere, for reports. example, have we found references to a peculation of asbestos workers, although several authors who have quoted the ob served incidence of lung cancer in autopsies of persons who also hod 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 came to autopsy. With the exception of a paper by Doll,*8 none of those reviewed gave am data on exjosure ami dust concentrations, and oven Doll's paper merely mentions With thi- understanding of the limit2:Mi> the existing literature with respect to epidemiological generalization, it may be of value to consider in somewhat more de tail ome representative earlier publications, a few of which were referred to briefly above. One of the most detailed studies and one which deserves the most serious considera tion is that reported by Doll*8 in 1955. This study reviews causes of death among asbestos workers based on coroners' rec ord?.. U al> attempts to estimate the risk lv studying records of men who worked for at least 20 years in exposed situations. Broun--Truon 635 A. M A AR( an l..s ()! 'STR/Af. Hl.Al.Th DoU concluded that iung cancer was a spe cific industrial hazard of certain asbestos workers and that, after 20 years of expo sure. the risk is 10 times as great as for the general population. This article is important for several rea sons, in addition to the definite conclusions at which it arrives. For example, it begins by stating that "in view of the infrequency of asbestosis, this large number of cases <61 cases of lung cancer) suggests--but does not prove--that lung cancer is an occupational hazard of asbestos workers." Neither this article nor any previous one which we have examined presents any fig ures to prove that asbestosis is an infre quent occurrence. Estimates of the number of persons potentially exposed to asbestos dust in the United States alone vary from 10,000 to 35,000, and the incidence of as bestosis of any degree might be higher than Doll imagines. This study, like so many others, involves autopsy records. The number of persons involved in the statistical analysis is only 113. representing only 1,042.25 man-years of life. It is also true that in selecting men who had been employed for at least 2U 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 Merewether and by Gloyne" In 19$ \ Gloyne *l 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. There were in his series 796 cases with sili cosis, and 6.9% of these also showed pri mary cancer of the lung. The incidence of lung cancer in other forms of pneumoconio sis Yas 6.7%. and in 169 cases which proved not to have any type of pneumo coniosis it was 8.3%. Gloyne considered "the mortality of the asbestos workers" to be "disturbing." First of all, it is obvious that the paper does not deal with the "mor tality of asbestos workers," and secondly, it must be borne in mind that all of Dr. Gloyne's cases were submitted to him for study because the findings were unusual for uncomplicated pneumoconiosis. It can reasonably be assumed that cases, including those of asbestosis, in which the findings were not considered unusual were not sent to Dr. Gloyne for examination. As a mat ter of fact, in the same paragraph in which he expresses concern over the incidence rate in asbestosis, Dr. Gloyne himself I>oint.s out that the rate for lung cancer based on necropsies at the London Chest Hospital was 21.3% while the figures of the Registrar-General showed only 2.4%. He thus recognized that autopsies on a cer tain selected group of cases were not rq>resentntive of the general population. It would seem, then, that notwithstanding the value of Dr Gloyne's work, its imjxjrtance 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 study pri marily l*r;tu>c they seemed abnormal by preliminary examination. 17. or 14.1G. had lung cancer Mereuetbe- - m 1^47. ;:i thi. rtqxirt of the !:'vcv.;c>f ot I`actorie>. reviewed all case- re]>rted beOAcen 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 re lucted up to December, 1954. by which time there were 344 Heaths, including 205 males and 139 females. Among them were 55 cases (16%) of cancer of the lung. 41 in males and 14 in females. It is quite possible that a large number of asbestotics who did not die of their asbestosis, or in whose 636 Vul. 17, June. AV /.CSC CAXCr.R !S ASBESTOS MISERS death certificate h was not mentioned, may prior to that date and enumerated a total have been missed. The import of this 16% 1 of 99. Eleven of these were those dis is enhanced by the simultaneous statement cussed by Doll M and may have been cases thru the incidence of King cancer in autop covered by other authors. Eight were dis sies of the general j>opulntion is only 1%. covered by Kennaway and Kennaway62 in The danger of attempting to compare a an analysts of death certificates, imd, 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,w who with Smith** had reported the first case in 1935, reported 4 cases of carcinoma of the lung in a series of 49 and the 17 by Gloyne contain some duplica tion with each other or with those of other English authors. autopsies on workers in an asbestos manu facturing plant who were shown to have "demonstrable deposits of asbestos in the Principles of the Epidemiological Method lungs." This, of course, is not necessarily identical with the disease asbestosis. Lynch, himself, points out that, although this is an incidence of 8.2%, "both figures are too small for very serious statistical types of Dorn * has pointed out that much of what is now thought to be pertinent concerning the comparative frequency of lung cancer in different population groups has been de veloped from the analysis of clinical ma 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 with asbestosis. It is also of interest that Klotz43 found only the same number of the reported impressions of various clini cians based upon their personal observa 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,'* esti the study of communicable diseases, that is mated that, of 309 cases of asbestosis in the to say, by epidemiological methods. literature, 44 showed associated cancer of the lung--giving an incidence of 14.2%. This is an illustration of generalizing an incidence obtained in a group of cases which were undoubtedly reported only be cause some of them showed lung cancer, to possibly hundreds of asbestotics whose In order to apply this method of investi gation to the problem under discussion, we were of the opinion that a study should be planned so as to provide (1) a well-defined population group: (2) available data for all members of this population, including the healthy as well as the ill; (3) a sample cases were never reported. The same ap plies to the conclusion of Teleky,** who appears to have reviewed reports of 39 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. which is truly representative of the popula tion; (4) reliable and valid observations relating to the problem of the study. A serious defect, common to most of the studies which have been reported, is that little or no Information concerning the healthy people in the group seems to have been 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.**`w workers, it is necessary for a study to in In 1955 he reviewed the cases M reported clude living persons as well as the dead. Braun--Truan 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 large samples, most earlier writers deviated from the epidemiological method and sought to circumvent the requirement of observing well persons by (1) compar ing the relative frequency of cancer in vari ous sites; (2) comparing the relative frequency of cancer in a group of hospital ized patients; (Z) 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 fre quency of cancer in various body sites, may resuit in finding a higher percentage r:m- frequency i in one of the groups, v.hen ir. :v:t, the Mortality 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 be found in another group of the same srie, 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 rqiorted by some authors may be miscon strued as applying to asbestos workers or even asbestos miners, when, in fact, the authors in question do not make this gen eralization, nor can the generalization be made for the reasons stated. Close study of the reports reveals that the percentages cited relate only to the group of autopsies covered by the particular investigation. The present study, in contrast to the earlier works, has been planned to utilize the epidemiological method. A well-defined group of asl*cstos miners has been estab lished in such a way that it constitute? a good 'ample of the whose population ol asbestos miners in Quclxc. 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, bur 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 638 Vol 17. Iu*f. /9.W AV s' 0 /./ A c; i'JXt f-.fi IX Mtxi Ks <li>*t;u^iions with the physicians in charge of the asbestos companies' programs and with clinicians, pathologists, representatives of City and Provincial health dejianments awl of the Canadian Cancer Society, and other interested |**rsons. Jt was found that morbiditv data, although somewhat limited, were available from such sources as the hospitals in Montreal and Quebec Cifv. and the 13 cancer detection centers in the Prov ince. However, because of the high mor tality in lung cancer, it seemed advisable tti depend tt)*on data relating to deaths. These we found to be obtainable at the vital statistics dejwrtmem of the Miuistn of Health in Quebec City. Prom the pre liminary survey, it was apparent that exten sive and detailed information cottld be gathered with res[ect to both the jarsons employed in the asbestos mining industry and the mortality figures for the general population. Following thi> exploratory survey, the initial effort whs directed to the collection of data relating to all workers who had been processed through the clinic at Thetford Mines since its inception in 1947. and similar information regarding all workers at Asbestos. Que. Data Pom the clinical records included the age, fantilv and per sona! medical historic*, smoking habits, number of years of expn-urc, an estimate >f weighted exposure, and the course of the individual's health status or the cause of his death From this information it wa> |*ible to formulate a "cohort" which could !>e well defined, should be representative of the whole group, and could be followed for a definite period of time. AH of the available experience indicates that the development of asbestosis in less than five years of ex posure must be somewhat rare. Accord ingly, the cohort was defined as including every miner who had a total exposure 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 w;ii then followed by means of the annua! physical examination records through a six-year interval, 1950 through 1955. All data regarding this group were then tabulated in order to determine the characteristics of the cohort. For those who survived the entire period, reference was made :o the physical examination results and x-ray findings at the end of the f>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. Eventually, all but a small number of these were accounted for as either living or dead, ;ul 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 case? in which death was certified as having been due to pri mary cancer of the lung were examined for 'uch information as place of residence, occupation. <Ui> o; denth, hosjv.ta' 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 instance? 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. Broun--Tman 639 /*/ ba a. m. a ARCmn:.s o/: ixdlxtrial hlaj.uj From them, death rates for the general population of Quebec and of individual counties were calculated for specific years and analyzed by cause. Practically all employees of one company are covered by a group policy of life insur ance which, fortunately, nearly all of them continue to carry when they retire. A very few are not covered by this policy, and those who leave the industry for one reason or another except retirement usually are no longer covered, but this is likewise a small number. As an additional check upon the information obtained from the clinical records on this group, .the records of the life insurance company were examined for all death claims paid under the policy, and particular notice was taken of the claims in which the proof of death was based on cancer of the lung. Deaths from lung cancer among asbestos miners were thus determined from the clinical records in the medical service of the industry and checked by means of the death certificates and insurance company records, "'"he deaths were then verified individually oy reviewing them with the physicians in charge of the medical services. In this man ner, there was established a list of cases in which primary cancer of the lung is con sidered to Have been proved as the cause of death. A few cases in which lung cancer is strongly suspected but not proved as the cause of death were considered separatelv. Mortality rates have been calculated using both the "proved" and the total of "proved" and ''suspected" cases during the rears un der observation. Comparisons were then made between the death rates from the same cause among specific segments of unex>osed persons. AN 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 known from the clinical records, such as family history of cancer, personal history of heavy smoking, coexistence of asbestosis, or exposure to asbestos. In addition 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 well as ever)- 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: Orteinal Cohort l,,ost Person$ PctluctfU Final Cohort i.ivute '> 195$ (orVi<v aix) rtiirnO 1 >rd by I9SS Canter of Sun* canor or 1 ,,, Oilwr tausts t'nknnwn exustt \vo*inoktrs t 'nknow it (.091 133 5.958 1.771 187 9 3 169 6 *.633 1.265 20 Tables 1. 2. .1. and -4 r -t-wn; age. number of years of eniplnvment wcigfved average c\|>osure. and -mokmg habits of 'he 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 nf exj>osure based on a weighted average of the years $|>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 Vot. 17, /*. MX AV LUNG CANCER IN ASBkSTOb MISERS Table 1 --Number and Percentage Dish ibut\on Table 2.--Number and Percentage Distribution by by Age i Length of Employment Ace ...... 46-64................................... ......... 65+..................................... UetMirn-......................... ......... A*er*cr aic....... -............. Number 3.90! 616 $.464 Lee than 0J%. Per Cent 66 IV 10 $ * ico Lenflb of Employment 6-9 ..................................................... KH9..................................................... -39................ .................................... 30-39..................................................... H..................................................... 60+....................................................... Touts..................................... A*enc yean ofemployment......... Number 1.746 Z39* 932 tea 166 66 6.464 Per Cent SO 40 16 10 3 1 too areas. For the purposes of calculation, the assumption has been made that the relation ship between these categories is linear, and that Category II is twice as dusty, and Category III three times as dusty as Cate gory f. uaJly smoking more than five cigarettes per day. Persons who smoke pipes or cigars exclusively were not considered to be smok ers for the purpose of this study. Table 5 presents the year-by-year ex perience of the cohort and indicates the Table 3.--Number and Percentage Distribution by Exposure Category Table 4.--Number and Percentage Distribution by Smoking Habits Exposure Ceucory I......................... ................. ........... It........................................... ........... Ill.......................................... ........... Unknown................................ ........... Touts........................ ........... A verve Exposure................. Number 3.031 3.160 1.772 6 5.464 Lee than 0.1%. Per Cent 34 34 30 # >00 Smokrnt Habus Smokers....--............... NoanaoKers................. Unknown.................... Touts.............. Lee then 0-i%. Number 4.673 1.364 20 6B54 Per Cent 74 21 100 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 refers to a cigarette smoker, habit- number of deaths each year from specified causes. In general, a case was considered to be "proved" as one of primary' cancer of the lung when the records showed that the diagnosis had been supported by an 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- TaBLE 5 -- Ycor-byYcor Experience cf Cohort and Death Rates per lOQ.OOO Man-Years of Risk Year No. Alive At Becrantnc of Veer Proved Primary Ce. of Luftc I960........................... 1961............................ 1952 ......................... 1463........................... 1964........................... 1965............................ 6.964 5.941 6.922 6.443 6.444 5.410 l 3 0 2 1 3 Touts........ . 9 e "Proved" nie per >00,000 tun-year*of rt* isjpl T " *Toul" nu per 100.0UQ uR.yun ot rok Cause o< Death Suspected Primary Ce.of Lunf Other Causes 2 12 0 t? 0 37 l 34 0 33 0 36 3 169 Unknown i 1 0 0 4 0 6 Men-Yean of Risk 5.960 6.932 6.903.6 $.866.6 6.829 5.790.6 36.371.6 5rau--Truan A U A ARCHIVE* Of INDUSTRIAL HEALTH Tabu 6.--"Proved" Cases of Primary Cancer of the Lung Ceae So. 1 2 3 S 6 T 8 8 Aft 06 6$ 66 69 48 61 66 37 68 Smoker Yes Yu Yu Yu Yu Yes Yes Yes Yes Exposure 26 yr. to Cei. 11 34 yr. to Ci. 1 37 jt. u> Cei. 1 32 yr. Is Cei. 1 22 yr.In Cei. 1! 33 JT. in Cei. Ill 30 yr. ta Cei. 11 to yt. ts Cei. 1 28 yr. Is Cal. Ill Died 10-12-51 5- 3-56 7-20-55 8-20-60 -51 4-30-.13 11-22-63 8- 6-54 6- -66 Autopsy Yes Yes No Yes Yes Yes Yes Yes Brooch. Astesiosis Yes No No No Yes Yes Yes So 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" case? in interpreting the results of the calculations is desirable before fur ther discussion of the mortality rates which are derived in later tables For example, it happen- that the rate found for the proved cases is close to the "expected" rate based on the general population figures for the Province, as will be shown later, and on this basis we should find eight deaths from lung cancer among the cohort. Actually, nine cases were observed. If, however, the 3 additional "suspected" cases were in cluded, increasing this figure to 12, the total would be very close to the 95% 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 lung case was certified as having died by rra-ou of hydrothorax, possibly due to lung t'rr but agarr there was no surgery and no postmortem examination. In th- third ci's. although it was subjected to auton>y. two pathologists disagreed as to whether lung cancer was present. The death was certified as having been due to chronic myocarditis with nephritis and pulmonary congestion, and possibly cancer of the lung. On the basis of these facts, it seems unwar ranted to include these three cases among Table 7Suspected" Primary Cancer of the Lung Ceee No. i 2 3 Ate 49 46 66 Smoker Ye* Yes Yol Exposure 32 yr. ta Cet. til 33 yr. tn Cel. Ill Cyr.laCecn Died 10-26-60 7- -63 9-30-56 Autopsy No Y'es No Asbestoss No Yes No 642 Vol. 17, June, mg 7 -I 6 I.l C.-1XCHR JX .iS'Hl.sros' MfA'liRS "proved" instances of lung cancer. On the other hand, they cannot, in fairness, be dis regarded completely. It is for this reason that mortality rates have been calculated lv>th 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" cases reported for a total of 240 men dur ing the six years, or about 1440 man-years of exposure. When the "susi>ecte<r* cases are added, one case does show up in this Table 8.--Lung Canter Death.t by Age Groups I able (f.--Lung Cancer Deaths by Length of Employment Number of Persons in<J Number of Lunt: Cancer Death* I^enetli of Employment No. of I'enons No. of Death* Proved Toutl 4-9............................... HM*............................... 30-29............................... 30-39......... 40-49.................. . Me........................... Touts........ 1.7*4 2.396 922 603 IBS 54 4.946 0 1 3 5 0 0 0 1 3 7 I 0 12 Annual l.unc Cancer Death Rate* per 100.000 Man-Years of Exposure Lonxth of Employment VroeoO Total 4-9............................................ 10-19...................... 20-29........................................... 30-39........................................... 0-49.......................................... 40+............................................ 0 193 90 Over-ell...................... 34 Number of Person* and Number of Lunir Cancer Death* A<e Orvup No. of I'enons No. f r>aihi Proved Toul 20-44................. .. .. 45*54........................... 14 -to........................... 5+............................. 1nknown.................. 3,901 U24 A14 314 3 i i s 4 U 1 3 s s 0 Touts......... 4.94b y 12 Annual I.unc Cancer Death Rate* per 100.000 Man-Years of Exyosut* A Be froup novel I'OUl 20-44.......... 44-54... . 54-W............. 04+ .......... l- tikrxiv'ii... .......... Uvcr- all............................. 1 15 n\ 212 U _ 25 4 44 l 205 n 3 period ThU would produce a rale of 69 per 100.UOU, again demonstrating the im portance of these questionable, but un proved, cases to the final conclusion, liecaus-;:. if there were no cases in this number of men with long exjwsure, 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 othT 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 being a carcinogenic agent, for, if exposure to asbestos is in any way con nected to lung cancer, we would expect that the longer and heavier the exposure, the higher the rate that would be found. The only possible error in this interpretation could occur if the weighted exposures were inversely related to years of employment, Tahi 10 -- l.uni; Cancer Deaths by Exposure Category Number o; Pr'i'm an,! Number cf Lunc Cancer Deair* Exposure Caieeory I............. inn.......................................... Unknown.................... Touts............ No of I'ersons 2.031 2.140 1.772 4 4.94b No.ofDenths Proved Total 44 34 74 00 9 12 Annual Kune Cancer Death Rates per 100,000 Man.Years of Exposure Exposure Category Proved Tota .11t ..................................................................... ................ lit............................................ .............. Unksown.......... . 33 23 19 33 31 37 0 Over-all..................... .............. 24 34 H rrtupf--Trutin 643 /'-V A. M. A. ARCHIVES OF INDUSTRIAL HEALTH TAdLf 11 --Number of Persons in Various Weighted Exposure Categories by Length of Employment UoehOteltdXoEnxpwosure Length of ----------- -- Employment l 11 lit 5-9 10-19 20-29 30-39 <0-9 504- to; 593 490 663 683 651 314 363 243 247 218 137 76 67 41 >4 21 10 Totals 2.031 twite yean of exposure 174 2.150 174 1.772 16.6 Un known 0 l 2 l 1 0 5 29.0 Total 1.795 2.393 922 603 185 55 5.956 174 in which case the heaviest weighted ex posure (Category 111) would show the shortest length of employment. Table 11, which lists the number of persons in various exposure categories by length of employ ment indicates that this error has not oc curred. In fact, the average number of years of employment for each exposure category' is almost identical. Table 12, which develops the rates for smokers and nonsmokers, is most striking. It shows that not a single case of lung cancer developed among the 1265 nonsmokers and that all cases of lung cancer, both "proved" and "suspected," occurred in smokers. Table 12 was so striking that it was felt that further verification was necessary. It was possible that some abnormal distribu tion may have occurred, e. g.. the non- Tasle 13--Number and Percentage Distribution Smokers ana Xonsmokcrs by Age Groups 4.-S*. 4. (yS-- ......... f r.tnou n.............. Totals.......... A-eerac* asc.............. Number Smoker Nonsmoker 3.?- 8W u l(A 2 669 224 202 150 0 4.673 394 1.265 44.2 Unknown 12 4 2 l l 40.7 Table 12.--Lung Cancer Dtash for Smokers and Nonsmoktrs Number of Persons and Number of Lung Cancer Deaths by Smoking Hahns No. of Deaths Persons Proved Total Smokers.................... Nonsmokers............... Unknown.................... 4.673 ijfij JO 9 12 00 00 Totals............ 4,946 9u Annual Long Cancer Death Rates oer 100.000 Man-Years of Exposure by Smoking Habits No. of Deaths prored Total Smokers....................................... Notumokers.............................. Unknown..................................... 43 0 0 OW4ll.......................... 34 smokers may have included a larger percentage of young men. Consequently, ad ditional Tables, 13, 14, and 15 were con structed to show the distribution of smokers and nonsmokers by age, length of employ ment, and degree of exposure. Although there are slight differences, they do not account for the fact that all observed cases of lung cancer were in smokers. In respect to age (Table 13) the combined average age of the smokers was 4.9 years less than that of the nonsmokers. Table 14 shows that as far as length of employment is con- Table 14--Number and Percentage Distribution of :ts o(i Sonsmokers by Length of Employment Leneth of Employment 5-9.................. 10-19..................... 20-J9..................... 30-39..................... 0-49..................... 50+....................... Totals.... Average length of espiopTDem.... Number Smokers i.40 1.967 722 433 no 3.1 Vonsrooke? i ir: 426 199 166 7.1 ** Unknown 1C 4 2 4 0 0 4.673 1.265 20 19.3 16.0 Percentage Distribution Ate Croup Smoker Konsmoker 20-44.................... ....... 45-54.................... ....... 55-64.................... ....... 95-*- .................. ........ Unknown........... 68.5 19-2 8.6 3,5 54.5 17.7 16.0 11.8 0.0 Totals... ....... 100% 100% Unknown 60.0 20.0 10.0 5.0 5.0 m% * Less than o.os%. 644 Percentage DtorttmWft Length of Employment Smoker Nonsmoker 4-4 ............................ 10-19............................. X-29............................. 3<V39............................. 40-49.................................. SO+.................................... 30.1 4J.t 15.4 9.3 2.4 0.7 29S 33-7 tS-7 13.1 4.9 U Total*........... 100% v% Unknown SO O X.O 100 20.0 0,0 0.0 \co% VoL 17, June, 195* LU SC CASCER IS ASBESTOS MISERS Table 25--Sumber and Percentage Distribution of Smokers and Sonsmokers by Exposure Category Exposure Cetetor? I.................... 11..................... ....... Ill.................... . Unknown................... Totals... ....... A*er*ce exposure eatater?........ . Number Smokers Nonsmokers 1.601 4 474 432 338 1 4.673 1.265 2.0 1.0 UoLoowa 4 0 0 20 2-3 Porenute Distribution Exposure Caictor? 1...................... II........................ ill...................... Uaksowp............. Smokers 36.2 0.1 Notumokers 37.3 33.7 26.T 0.1 Totals.... 100% 100% Unknown 30.0 33-0 43.0 0.0 100% cemed, the smokers had worked about 2.3 years less on the average than the nonsmokers. With longer exposure and greater age, one would 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, Dotr.inion of Canada, and the United States.-- In order to make a comparison of the experience among asbestos miners with that of the general population of the Province of Quebec, statistics were gathered, as stated earlier, tn 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 1930 through 1955, and shows the annua! rate per 100,000 in these segments. It will be noted from the table that the' mortality rate for the "proved" cases in the cohort is only slightly higher than the rate for the Province. When the "suspected" cases are included in the calculation, the rate for the cohort rises to 33.8 per 100.000, which is about 50% higher than the rate for the Province. This, it will be recalled from the previous dis cussion of the 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 total 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 vears 1954 and 1955 were'thought to be more nenriv representative of actual condi tions /y.:Ue likely that the gener.r. r.<~: studlvd for lung cancer wr. the same diligence with which t Ta*& 16.--Comparison of Cohort with province of Quebte Province Cobon Total Proved Province (etrludlac aebeew* workri) Number of -- -- Persons 1930 1.198.000 * 3.923 t 1.193.000 196 3 J 193 1931 230 2 2 2)6 Loot Cenoer Deaths . --......... 1932 1033 1944 1933 243 303 303 337 03 I 3 02l 3 243 300 302 334 Total 1,624 12 9 1.612 Annoil R*te per 100.000 V* 33.8 2.1.3 22.3 la the Provtae* (Stum. it has bow assumed all mak iuu aim daaih* are lor sea of JtH- yean. Approximate midpoint of the enumerated population tor 1931, sad ibe estimated population for 1944 (Rapport, Pit. be la De> mocraphie). INuiriber alive la cohort et beflnntng ot 1932. Bra**--Truer* r-v / .2, b tie Group 20-44 45-54 55-64 65+ Totals A. M. A. ARCHIVES OF INDUSTRIAL HEALTH Table 17.--Lung Cancer Deaths for the Province of Quebec* Population 777.000 2CC.UQ0 137.000 ns.coo 1.237.000 Number of Deaths 1954 Toul Certified Specified Primary Toul Proved Toul Proved 17 13 11 9 67 36 43 29 100 38 69 32 111 33 as 29 295 120 191 99 1955 Toul Certified Specified Primary Total Proved Total Proved 17 9 17 9 60 35 56 22 117 57 116 1m4m8 54 148 54 342 155 337 153 At< Group 2D-44..................................................... 45-64..................................................... 55-64..................................................... 66+......... ........................................... Over-all..................... Death Hates per 100,000 1954 Toul Certified Specified Primary Total Proved Total Proved 73 53.2 73.0 91.7 23.8 1.7 17.8 37.7 27J 9.7 1.4 J1.3 30.4 U3 15.4 1.2 14.4 23.4 34.0 8.0 1955 Total Certified Specified Primary Tout Proved Total Proved 2.2 29.7 tt.4 1*2.3 27.6 1.2 17.3 4L6 44.6 u!i 7.7 37.7 64.7 122.3 272 1.2 ISA 41.6 44.6 \Z3 D*u trom death certificates. t Estimate (or population obtained By applylaj 1951 peroe&iaces (or t|i (roups for mala* to the toul populate lor 1954. as tiven io Rapport. Dir. <ie la Demopaphie. 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 total cases reported in 1955, a much higher percentage than in 1954 were specified as primary. The table also shows that a higher percentage of the total cases certified in 1955 were proved, again indicating increasing interest in this disease. A comparison has been made between the age-specific rates shown in Table 17, and those for the cohort, shown in Table 8. An average of the 1954 and 1955 rates for the Province has been used, since the 1955 figure was higher and may have been ex ceptional. 646 This comparison, summarized in Table 18, shows that the observed number of deaths in our sample is not significantly greater than the expected number of deaths, based on the average of the 1954 and 1955 figures for the Province. It is true that, in the case of the age group of 65 and over, the five deaths provide a figure which is almost significant at the 95% 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 18--Comparison of the Actual and Expected Number of Lung Cancer Deaths by Age Among Asbestos Miners Oroup Province Toul Specified Primer* Rate per 100.000 20-44 46-54 55-64 M+ Unknown 1.9 24.6 67.6 19J Obeerrod No. Expected of Deaths No. of No. of Mum Deaths * Proved Toul 3.901 1.124 615 316 3 ot 1 1 2 13 2 33 2 45 .. 0 0 The eipeeied number is based an th* everote of the IBM aod 1955 exe-epiwfie nut for the Promt* of Quebec, t Actually 0.4. Vol. 17, June. 1958 LL'S'G CAXCER JX ASBESTOS MIXERS Table 19 --Age Distribution of Adult Motes for Table 20--Annual Death Rates per 100,000 the Province of Quebec, 1951 Cancer of the Lung m Canada * .......i ll ' A Oroup 20-44.................... 15-M.................... 3S-+4.................... 63+..................... Total........ Province Number Tercenuie :r.ias lte.932 128.944 113.4*? *3 l* 11 >0 1.138.498 too fercentate in Cohort 66 19 3 100 * support. ISM. 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 643. Before leaving this comparison of the Province with the miners, it should be shown that their age distributions are rea sonably the same. That this is the case can be observed from Table 19. It should be remembered that the miners retire and consequently, it can be expected that the oldest age group will be larger in the general population. The data presented in Table 20 indicate that the lung cancer rate generally decreases after age 70. There fore. we could expect the rate for all people over 65 to be smaller than the rate for the group between 65 and 75. which would apply to the oldest group of miners. It is felt that by using the whole adult male popula tion. we have developed rates for the gen era! oc.p-j'ation which are somewhat lower than i: wc 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 ips 79 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 Oroup Under 30 SO-M 36-39 40-44 43-49 SO*$4 36-39 60-64 64-69 70-74 73-79 10-64 14+ All Apes 1931-1933 0.3 0.9 3.0 30 4.2 6-3 13.7 I3.S l.Vl 10.7 13.8 84 11.4 3-8 Group* ot Yun 1941-1943 04 0.9 34 S.4 13.3 18.9 374 33.7 M4 30.6 30.0 37.9 HJ 7.1 1930-1933 1.0 04 6.3 16.7 374 39.7 77.8 103.9 8*4 83.9 39.7 71.0 13.8 * 'Mortality from Lung Cancer in Canaria." 1931 to 1937. increase is particularly marked after age 50, confirming an observation previously made, to the effect that until recently lung cancer has probably been underdiagnosed in the older age groups in the general 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-> 4S44 SS+4 6S + Rate S 4^ 69 90-95 These rates are, in general, lower than those developed for the total (proved and suspected') cases of lung cancer among the asbestos miners. The only large difference, however, is in the age group of 65 years and over, and it is quite possible that the rate tor this group may have increased for Canada between 1952 and 1954 as it did for the Province of Quebec fTable 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 A At. A. ARCHIVES OF INDUSTRIAL HFAITH T.vBle 2\ --Number of Deaths and Death Rates /. iOQ.OQft by Age Groups for the Adult Male Population of the United States A(t Qroup 20-44 45-M 6W* (5-r Toul Population 24.544.000 ft.0U.UU) (.540.000 $.670,000 44.(18.000 Cams M t.VTV (.2(4 6,4*3 16.M0 Uste per l< 3.6 36.0 06.( 114.3 37.2 ' Oau (rom *avtui StAUso ! tb Cawed And 2. 1852. Vol. V asbestos miners in this stud}'. It is there fore obvious that there are no important differences between the rates for asbestos miners and those for the general population of Quebec and the Dominion of Canada. Since it is probable that figures for the United States are more complete and, there fore, possibly more comparable to the data for the miners, age-specific rates were com puted from "Vital Statistics of the United States," Volumes I and II, for 1952. These rates have been tabulated in Table 21. It is apparent that these rates compare favorably with those for the asbestos miners as shown in Table 8. Still other rates for the United States were obtained from the American Cancer Society, and for males, these were 25.3 per 100,000 in 1953, and 28.0 per 100,000 in 1955. They are not identical with the rate calculated from the figures of the office of Vital Statistics, but this is possiblv because the American Can cer Society rates are for males of all ages. .Yevertbeicss. the}-, too. compare favorably with the rate- of 25 for 34 tor total cases') ''btamme amonc me asbestos miners. Turning tor a moment to a comparison between the asbestos miners and persons who are exposed to asbestos in one form or another fas distinguished from the gen eral population groups just discused, who have no exposure) an interesting observa tion can be developed by deduction. Hueper 5* 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. With workers in Africa, Denmark, Nor 648 way, and other countries, at least 50,000 persons must be exposed throughout the world, and it can be assumed that this number has been fairly constant in the 20 years since 1935 when the first case of asbestosis with lung cancer was reported. At least 1,000,000 man-years of exposure has thus been accumulated, and this figure can be divided by the approximately 150 cases of lung cancer with asbestosis re ported during the 20-year period. This gives a rate of 15 per 100,000, which is at least indicative that any lung cancer rate which can be calculated for workers ex posed to asbestos dust is not much greater than that for the unexposed population. Comparison Between Eight Counties Ad jacent to the Asbestos-Producing Areas and Eight Selected Counties.--To compare lung cancer mortality rates in the counties sur rounding the asbestos-producing areas with another group of counties in which no as bestos miners are likely to reside, the rates were computed on the basis of figures for the years 1950 through 1955. The eight counties selected for comparison were Argenteuil, Chateaugav. Montmagny, Portneuf, Richlteu. Rtviere-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, Fromenac. Megantic. Rich mond. Sherbrooke and Wolfe Table 22 show? thi mjmbvT of iung cancer deaths for the year? 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 27, June, 1958 / U'XG CAXCER IX ASBESTOS MIXERS TA8LE 22.--Xumber of Lung Cancer Deaths ond Rate per 100.000 Man-Years Couaues Mt*nuc Counts Eicbt "Ad|*ccnt" Counties E4bv Selected CounUt* Pro*ioc* of Quetec Prtmoe* of Quebec teljbt 'idjeceot" eounties Mcoueal el Ute tie Jesus Population 1962 13.ICC 97.600 83,000 1.198.000 1.100.000 394.000 1960 3 6 2 196 190 3 1961 1 3 10 230 nr i Ml* Lon* Cancer De*ths 1952 3 9 3 346 236 168 1963 3 16 18 303 SET 192 1964 1 4 5 303 299 186 1966 4 16 9 337 341 225 it u aouAcd ibat aU male iunc esooer deaths oosumd after ac< 30. Total 16 64 49 1624 15*0 770 Raie Per 100.000 18.9 9.4 94 22.6 23.6 324 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 only possible conclusion from this comparison is that there is no evidence that the persons who live and work in the coun ties surrounding and adjacent to the as bestos-producing areas have any greater incidence of lung canceT than those who live elsewhere in the Province. Comment on AH Recorded Lung Cancer Cases, Living and Dead, omono the Asbes tos Miners.--Although a simple enumera tion of a!! the known or suspected cases of cnnc<sT 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 im-e^igation, 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 lit, and six worked in an exposure represented by Category 1. There were only 17 among these provrd 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 WJB'.'IJ.V .B ^ 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 asbestosis were both present. As additional cases in which the two diseases coexisted were reported, a causal association appears to have been gradually accepted by many authors, although some workers considered the correlation to be inconclusive. The pres ent study was undertaken in an effort to de termine whether a causal relationship did, in fact, exist between exposure to asbestos and cancer of the lung. Since most earlier studies had been limited to enumerating the lung cancers found in certain selected samples, such as cases coming to autopsy or death certificates in which asbestosis was mentioned, it was apparent that they could not fulfill the re quirements of an epidemiological and sta tistical approach to the problem. The present study was, therefore, designed to meet the requirements of this method. After a preliminary survey to explore the availability of reliable information, data were gathered on workers in the asbestos mines in Quebec, based on their medical records A cohort was defined as a group of asbestos miners having at least five years of exoosure and who were in the industry in 1950. Data relative to their characteristics were collected and their status at the end of a 'ix-vear period of observation was de termined In the case of those who had died, an exhaustive search of death certif- and insurance record? was earned 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 likely that such cases would not be included in the statistics for the general population and because they influence the results so mark edly. According to the findings in this study, the mortality rate from lung cancer does not appear to increase with length of ex posure or with degree of exposure, a fact \\h\h t'-e'-vn? strong evidence against the carcinogtenicirv 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, hmt. 190* / 7 rfJL, o ICXC CAXCER IS ASBESTOS MIXERS of 37.2, 25.3. and 28.0 obtained from various sources for adult males in the United $;ates. Finally, in this matter of comparison, it would appear that the world-wide experience of persons exposed to asbestos dust is not worse with respect to lung cancer than that of the unexposed population. The counties surrounding the asbestosproducing areas, in which it is presumed most of the asbestos miners live, have al most identical mortality rates with those of eight counties widely scattered through the Province, and are lower than those for the remainder of the Province, and much lower than the rate for Montreal. Since 1940 there have been 19 cases in which the diagnosis of primary cancer of the lung may be considered to have been proved. Approximately half of these cases were associated with asbestosis. All but one 6. Behrens. W., Experimental Asbestosis. Schweiz Zisciir. allg. Path 14:275-297. 1951. 7.i Behrens. \\\, Jr.: The Clinical Picture and Pathoiugj of Asbestosis, Ztschr. Unfailmed u. Rerufskrankh. 45:129-140 (June 15) 1952. 8. Berbluiger, \V.: Increase of Lung Cancer and Diseases Due to Dust Inhalation, Med. Klin. 27:1337-1342 (Sept. 11) 1931. 9. Berenbium. I.: Irritation and Carcinogenesis, Arch. Path. 38:233-244 (Oct.) 1944. 10. Bohne: Asbestosis, Deutsche med. Wchnschr. 62:928-930 (June 5) 1936. 11. Bohme, A.: Results of Periodical Examina tions of Workers in an Asbestos Factory, Beitr. Silikose Forsch. 11:34, 1951. 12. Bowles, O.: Asbestos-Milling, Marketing and Fabrication, Information Circular No. 6869. U. S Department of the Interior, Bureau of Mines, 1935, pp. 1-26. 13. Breslow. L.; Hoaglir., L.; Rasmussen, G., and Abrams. H. K.: Occupations and Cigarette Smoking as Factors in Lung Cancer. Am. 1. Pub. Health. 44:171-181 (Feb.) 1954. died in the recognized "cancer-age" and at 14. Bristol, L. I.: Roentgenologic Aspects of least one-third had only the lightest ex Silicosis and Asbestosis, A. M. A. Arch. Indust. posure i Category I) to asbestos dust. Health U-.189-19$ (March) 1955. i On the basis of what are believed to be 15. Cancer of the Lung: An Evaluation of the Problem, Proceedings of the Scientific Section, complete and reliable data, it seems fair to Annual Meeting, American Cancer Society. Inc.. 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 operation? i? comparable to that in areas widely scattered throughout the Province of 16. Cartier. P.: Asbestosis Cancer of the Lung, in discussion on Smith. \V. 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 i? lower than in some urban ized area< within the Province. 18 Clerens. I : Research into Pulmonary- Asbes tosis in Belgium, Arch beige* med Sociaie 8 55756? < Nov ' 1951 REFERENCES 1. Alascii' Escobar. R: Bronchial Carcinoma Review of 200 Cases, ,1. Internal Coll Surgeons 26:375-379 (Sept.) 1956. 2. Allen, M. L.: Bronehiogenic Carcinoma As sociated with Pneumonoconiosis: Report of 2 Cases. J. Indust. Hyg. 16:346-347 (Nov.) 1934. 3. Cartier. P.: A Contribution to the Study of Asbestosis. Arch. mal. profess. 10:589-595, 1949. 4. Anderson. C. S., and Dible, .?. H.: Silicosis and Carcinoma of the Lung, J. Hyg. 38:185-204 (March) 1938. 5. Baader, E. W.: Asbestosis, Deutsche med. Wchnschr. 65:407-408 (March 17) 1939. 19 dyne1:379. 1951. and hdicirvv Ur:- M J 20 Coffin. G. J.; Dumee, H. C.: Maicr, H. C.; Pardee, H. E. E.( and Wynter, E. L : The Effects of Tobacco Smoking. Panel Meeting. Bull. New York Acad. Med. 32:133-156 (Feb.) 1956. 21. Cohart, E. M.: Lung Cancer and Economic Status, Cancer 8:1126-1129 (Nov.-Dee.) 1955. 22. Cooke, W. E.: Pulmonary Asbestosis, Brit. M. J. 2:1024-1025 (Dec. 3) 1927. 23. Cureton, R. J. R.: Squamous Cell Carcinoma Occurring in Asbestosis of the Lung, Brit. J. Cancer 2:249-253 (Sept.) 1948 24. Cutler. S. J.; Schneiderman, M. A., and Greenhouse, S. W.: Some Statistical Considera- Braim--Tntan 651 /v A. M. A. ARCHIVES Of INDUSTRIAL HEALTH tions in the Study of Cancer in Industry. Am. J Pub Health 4-4 1159-1166 (Sept.) 19S4. 25. Davies. D. F.: Current Status of Lung Cancer Research: Some Pathogenetic Aspects, CA 6:169-174 (Sept.) 1956. 26. Desmeules, R.; Rousseau, L.; Giroux, M., and Sirois, A.: Asbestosis and Pulmonary Cancer, Semaine de. hop. Paris 23:1820-1823 (Aug. 7) 1947. 27. Doll, R-: Bronchial Carcinoma: Incidence and Aetiology (Milroy Lectures, abridged), Brit. M. J. 2:521-527 (Sept. 5); 585-590 (Sept. 12) 1953. 28. Doll, R.: Mortality from Lung Cancer Among Asbestos Workers, Brit. J. Indust Med. 12:81-86, 1955. 29. Donnelly, J.: Pulmonary Asbestosis, Am. J. Pub. Health 23:1275-1281 (Dec.) 1933. 30. Dom, H. F., and Cutler, S. J.: Morbidity from Cancer in the United States, Pub. Health Monograph No. 29, P. H. S. Publication No. 418, U. S. Public Health Service, 1955, 121 pp. 31. Dom, H. F.: Cancer Morbidity Surveys: A Tool for Testing Theories of Cancer Etiology, Am. .1. Pub. Health 45:615-621 (May) 1955. 32. Egbert D. S., and Geiger, A. J.: Pulmonary Asbestosis and Carcinoma: Report of a Case with Necropsy Findings, Am. Rev. Tuberc. 34:143-150 (July) 1936. 33. Ellman, P.: Pulmonary Asbestosis: Its Clintcal, Radiological, and Pathological Features and Associated Risk of Tuberculosis Infection, J. Indust. Hvg. 15:165-183 (July) 1933. 34. Ellman, P.: Pulmonary Asbestosis. Proc Roy Soc Med. 34:557 (July) 1941. 35. Feil. A. Pneumoconiosis in Asbestos Workers, Presse med. 39:1872-1874 (Dec 19) 1931. 36. Fulton, W B.; Dooley, A.; Matthews, J. L.. and Houtz. 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, Pennsyivaiua Department of Labor and Industry, Bureau oi Indus:. Standards, Sept. 20, 1935. 3" 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. 4|. Gloyne, S. R.: Pneumoconiosis: A Histo logical Survey oi Necropsy Material in 1205 Cases. Lancet 1:810-814 (April 14) 1951. 4Z Gloyne, S. R.: A Case of Oat-Cell Car cinoma of the Lung Occurring in Asbestosis, Tubercle 18:100-101 (Dec) 1936. 43. Gloyne, S. R., and Merewether, E. R. A.: Asbestos, Occupation and Health, Supplement to Encyclopedia on Occupation and Health, Geneva. International Labor Office, 1938. 44. Goldblatt, M. W., and GoldWatt, J.: In dustrial Carcinogenesis and Toxicology, in In dustrial Medicine and Hygiene, edited by E. R. A. Merewether, London, London, Butterworth Sc 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.t and Angrist, A.: Bronchia genic 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. Hom, 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, Ztschr Krebsforsch 47:281-287, 1938. 52. Hueper, W. C. Cancer in Its Relation to Occupation and Environment, Bull. Ant Soc Control Cancer 25:63-69 (June) 1943. 53. Hueper, W. C.: Significance of Industrial Cancer in the Problem oi Cancer. Occup. Med. 2.190-200 (Sept) 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. 652 Vol. 17. June, 195S *T o Ll'NG 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 oi the Lung other than Tobacco Smoke. Dis. Chest 30:141-158 (Aug.) 1956. 60. Isselbacher, K. ; Klaus, H.. and Hardy, H. L.: Asbestosis and Bronchogenic Carcinoma: Report of One Autopsied Case and Review of Available Literature, Am. J. Med. 15:721-732 (Nov) 1953. 61. Kennaway, E. L, and Kennaway, N. M.: A Study of the Incidence of Cancer of the Lung and Larynx, J. Hyg. 36:236-267 (June) 1936. 62. Kennaway, , L., aod Kennaway, N. M.: Studies of Incidence of Cancer of the Lung and Larynx. Brit. J. Cancer 5:153-158 (June) 1951. 63. Klotz, M. O.: Association of Silicosis and Carcinoma of the Lung, Am. J. Cancer 35:38-49 (Jan.) 1939. 64 Lanza, A. McConnell, W. J., and Fehnel, J. W. -. The Effects of the Inhalation of Asbestos Dust on the Lungs of Asbestos Workers: Pre liminary Study, Pub Health Rep. SO. 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 Wedltr, H. W.; Occu pational Cancer among Asbestos Workers, Arch, path. Arut. 307:387-409, 1941. 68. Lynch, K. M., and Smith, W. A.: Pul monary Asbestosis: Carcinoma of Lung in Asbesto-Silicosis, Am. J. Cancer 24-56-64 (May) 1955 69. Lynch, K. M., and Smith, W. A.: Pul monary Asbestosis: A Report of Bronchial Car cinoma and Epithelial Metaplasia. Am. J Cancer 36 :567-3`3 ( Aug > 1939 70 Lynch, K M.. and Cannon, W. M.: Asbes tos Ar_vys:s o: 40 Necropsied Cases. Dts. Chest l-1 574-r.''-' (Nov-Dee.) 1948. 71 Mcr'hecters, S. B.. A Sur\-ey 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. 75. Merewether, E. R A.. Annual Reports of `the Chief Inspector of Factories, London, His Majesty's Stationery Office, 1947. 76. Merewether. . R. A., editor: industrial Medicine and Hygiene, London, Butte-worth & Co.. Ltd., 1956, Vol. 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 frem 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 Cancer with Special Reference to Silicosis and Asbestosis, Ccmpens. 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. Indust Hyg. 5:242-263 (March) 1952. 84. Stoll. R.; Bass, R, and Angrist, A. : Asbestosis Associated with Bronchogenic Car cinoma. A. M. A Arch. Int. Med. 88:831-834 (Dec.) 1951. 85. Teleky, L.: Occupational Lung Cancer, Acta Union internal. contTt Cancer 3.253-273, 1938; also, Zentralbl. Gewerbehyg. 27:33, 1940 86 Vorwaid, A. J.; Durkan. T. M., and Pratt, P. C.: Experimental Studies of Asbestosis. A. M. A Arch. Indust Hyg. 3:1-43 (Jan.) 1951. g7. Wedler, H. W.: Asbestosis and Lung Cancer, Deutsche med Wchnschr. 69:575-576 (Aug. 6) 1943. 88. Wegelius. C. Changes in the Lungs in 126 Cases of Asbestosis Observed in Finland Acta radio! 28:139-152, 1947. 89 Werber, M.: Pulmonary Asbestosis Asso ciated with Carcinoma. Zentralbl. 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 (Dec.) 1949. 92. Wynder, E L., and Graham, E. A.: Etiologic Factors in Broncliiogenic Carcinoma with Special Reference to Industrial Exposures; Report of 857 Proved Cases, A. M. A. Arch. Indust Hyg. 4:221-235 (Sept.) 1951. Browt' Tntan Primitd 04 Pnblukti m tkr Umittd Suttt wf Amrrie* 653 i I J i -5 2 fc* $ One further latoreatlaj observation from Table U'ie the ra:l;sr \ marked lacreaae la the total number of caeea for the Province berweca 1950 and 1955. It la aaeumed that at leaat part of thle lacreaae la due to Im proved recognition aad reporting of luag caacer during the interval. Tor thle reaeoa. the yoare 1954 aad 1955 were thought to bo more aearly repre- ' eeatatlve of actual coadltloae. Svea'ao* It U quite likely that the general population la not atudled for luag caacer with the aame dUtgeace with which IhU dlaeaae la looked for la the mlaere, aad It aeeme probable that the aertility ratee for tho Province may bo low. This would appear to be auhataatlaud by the fact that the reporting of caeee la the cohort showed no aueh laeraaae over the aame period. ,7 Tahlo lowaa compiled to ahow tho annual age-apeciflc lung caacer rate of caeee la which the death certificate merely read "eaacor el the lung", ea distinguished from thoae la which the diagaoele waa confirmed by autopey. surgery, er blopey. The term "specified primary** rofera to thoae eases In ^e theae two eategorlea la which the tumor wne specified ae having drlglaetod U tho lung. It will be noted that, of tho total caeea reported la 1955, a much higher percentage than la 1954 were epeeUlod at primary. The table aiao ahewa that a higher percentage of the total caeee certified la 1955 were proved, again indicating lacreaatag Utereat la thia dlaeaae. 0286 9 4w1 4. ^ 0 a 4 0 0 0|'M -- V' -- ^ ' *M 5-i W 0 i;l3V w a. K 4 4 |r* -- tf\ -- *>4 0 4 in "ij |H 4/ 0 *vl I >N 1i w -- 9 9* 9414 f*4 W9*> fi 5 N *4 0 0 . i 3!4 tm 4S u f. e [<m -- 0 z-- 4 5* 3 u to 41 491 00 4411 .! 4... i> 4 we -n 4 ow> 5 *3 u J a i: < H fg 4 9ta Q- fc 24 sa y 99 N 9 9 *^4* >la 2* WJ <4 44 41 9 ---- / <99 9l1--9' 49 vc9lfac aEW --4 _ 99 . "> J! u sil! 9 U fi. >. /40> <0M <m41(40/ 000---- 19/4 oOo Ooo Oeo Oeo r " / > J o. 5 S*>* 4La. <0 K 1& n c 0M e9 44 i* O " 9. a. 491 >to4 o -g v .5 Vi 41 4* I --41 O,11 00|| --0 --4 C -- Fto *. (to ( HS u 41 41 O II 44* 4f 141 c H c ww^ 00*4 0000 9 N 4 94r 2 ae. U* 4II0I0 r :uJ o1 441* 00 00 aQ 02S7 A eomparlaoa ha* been made between the ago-opecliic rates aiiowa ll 1 U Tibia 25, aad thoa# for the cohort, ahowa la Table y* Aa average of the 1)54 tad 1955 rate* for the Proviace haa beaa uted, alace th* 1955 figure higher aad may have beta excapcloaal. . \* ThU eomparlaoa, eummarlaad la TabU VdT ohowa that tba obaerved aumbar of daatha la our eampU la aot algalficaatly greater thaa the ejected aumbar of death*. baaed oa the average of the 2954 aad 2955 figure* for the Pvovlaca, It la true that, la the caae of the age group of 55 aad over, the five deatha provide a figure which l* almoat algslfleaat at th* 957* level. Hovaver, It ahould be soted that thle aumbar laeludoa oae of th* auapectad bet uapreved caae* prevloualy referred to. Furthermore, U la rather likely that the rate for th* geaeral population la uaderatated ia tbla age group, for the ebvioue reaaoa that the exact cause of deeth la the very old te not a matter f the tame lateaalty of latoroet aa It la la youagar peraoaa. TABLE IS Ago Oreo* Comparieoa of the Actual aad Expected Number of Luna Cancer Deathe by Are Among Aohecto* Miner* Proviace Expcctod* Obaervad No. Total Specified Primary Rate per 100. 000 No. of -' ' 1 No. of Minora Deatha of Death* Proved I util 20*44 45*54 55-64 454 Uakaowa 1.8 24.5 47.6 89.5 5901 1124 6)5 515 5 0? 2 2 -2 11 1- 3 35 45 00 Actually *4 a Th* axpoctad aumbor ta baaad oa Uto average of the 1954 and 1955 aga*apeclflc ratoa for the Provlaco of Quebec._____________________ 02SS . 39. 7kbit K ilio answer* & question previously raised, it ihvwi that msmbgr* of the cohort have sot died from lung cancer at as age earlier this the general population, and that such an explanation cannot be offered for the absence of lung cancer in 240 men with more than 40 years 1 cm. ploymoat referred to on page 26, Before leaving this comparison of the Province with the miners, it should be shewn that their age distributions are reasonably the same. That this is the ease can he observed from the following tabulation: fU 8L& /T Age Distribution of Adult Males for the Province of Quebec, 1951 (Rapport, 1954) A* Croi'p 20*44 45*54 $5*64 Tsui Province Humber Porecntaqo 727, 135 106,952 120,944 113,467 1, 150,496 63 16 11 10 To? Percentage In Cohort A- 66 19 10 $ 100 St should bo remembered that the miner* retire and consequently, |l can be expected that the oldest age group will bo larger in ths general popu. lilies. The data presented In Table yf indicate* that the lung cancer rat* (tesrillr decrease* after age 70. Therefore, we could expect the rate for ill people over 65 to bo smaller than the rate for tho group between 65 and 75, vhlcb would apply to tho oldest group of minora. It is foil that by using the heir adult male population, i have developed rates for the general popu* 0299 40 liticn vbirS are sussvhst lew tsaa 11 we test bera C1-* u ci-J tfci poepb la Us gsssrsl pepeUitoa ore? 73. A eoapariaea between Uo arbertoa aLcri ud tbe jxjpuUtlco d Us DcaUUa oa a wbela vaa aede, ulc; O ctntLctUal niUrrUl St/ i\ trota or?era! tweeae: caa scerco, Ptiillya (77) gava ago - aes - spoctHc rates fer Cassia lot Urea periods beteoaa US) and 1352. Rales lot aalea are gives Is Table $. AgtOrosp Vrdsr 30 $0-34 33-09 40-44 43-49 60-34 09-39 60-C4 03-09 70-74 73-79 90-04 93 plea All ages r- c^sutib >------------- ^r` //:* iwi-i-yq^ 1,* Grew* d Veers.. 104l-pa3 U63-i;3- 04 0.9 - 1 8.9 9.0 34 64 " - ` 18.7 13.3 13.1 10.7 1S.0 04 U.4 3.3 6.3 0.0 C-. y 8.3 6.4 124 L\0 ' '* 7 37.0 83.7 34.3 . 30.0 $0.9 27.9 M.3 7.1 10 O.S 3.0 0.3 10.7 / 7 87.2 83.7 77.3 102.9 36.3 68.9 r>../ 59.7 71.0 i3.fi 2* Mertaitty iroa Lay ccceer la Csunda '21 to W32*. 02SO / \\ \ 41. These figures show strikingly the Increase la rates betweea i951 sad 1952, tad this laereaee Is particularly marked alter age 50, confirmtag aa observation previously made, te the effect that until receutly lung tsacsr haa probably been uadcr-dUgaosed ia the older age group* la the jtaeral population. To uao those figures for purposes of eomparisoa, it is accessary / t* comblae the rates for certain age groups la order to conform to the age tlitrlbutieos used la this study. Siacs the exact populatioo* la eaeh age group tor the years Indicated Is not kaowa, this must bs as approximation. However, to* rates would bo somewhat as foUowtt Age Croup 20*44 45*54 55*64 65 Rato 5 27 65 50.95 These rates ars, Ufgoaorai, lower thaa these developed for ths total (proved end suspected) caeet of luag cancer among the asbestos miners, Ths only Urge difference, however, U la the age group of 6$ years ted over, tad U Is quite possible that the rate for thie group may have increased for Caaada betweea 1952 and 1954 as It did for ths Province of Quebec. {See Table >*0/7 0291 42. A further eorr.perl*on Ha* been made with as over-all rate obtained from the Americas Cancer Society for reapiratory cancer death* in Canada ri U 1933. Thti rate, for male*, U 20.8 per 100,000. five more per 100,000 (haa Phillip*' 1930*1952 rate, aad compare* with 25.3 per 100, 000 for proved ***** aad 33.8 per 100, 000 for total case* among the atbeate* miner* la thi* *tudy. Jt U therefore obviou* that thero are so important difference* between lh* rte* far eehestoa miaere aad tho*e for the general population of Quebec aad the Dominion of Canada. Since it ie probable that figure* for th United State* are more complete aad, therefor*, possibly more comparable to th* data for th* miner* *l.(pacific rates were computed from "Vital Statistics of th* Uaised State*", JL Velome* 2 aad 11, for 1932, Those rat** have bees tabulated la Table K, <1/ TABIX Number of Death* aad Death Rate* par 100,000 by Ag* Croups for the Adult Male Population of the United States*--Data From -Vital Statistic* 6f the United State*". Volame* 1 and U, 1952 Aje Croup 20-44 45.54 39.44 45 4 Total Population 24, 544, 000 8,045,000 4,340.000 5.490.000 44,419.000 Caaes 883 2979 4254 6403 16,599 Pate per 3.6 36.9 98.6 114.3 37.2 \ \\ \ i 0292 43. It i eppsrent that the** rate* cnmpirt favorably with :ho* (er t the asbette* miner* a* shown is Table V. Still otbr<raie* for tbe United itftfi were obtained from the Americas Cancer Society, end for n.aUe, thei* were 25, 3 per 100, 000 la 1953, end 28. 0 per 100,000 In 1155. Tbey are not identical with the rata calculated irom the figure* of the office of Vital Statietice, but thie la possibly because the American Cancer Society rate* are for male# of all agee. Nevertheless, they, too, compare favor* *bty with the ratee of 28 (or 34 for total caeee) obtaining among the aebeetoe mlnere. Turning for a moment to a comoarieon between the aebeatne mlnere 1*4 parson* wbe are exposed to aebeetoe in one form or another (ae die* llAgiilfbed from the general population groups Just difeuseed, who have no (56) eipocure} an Interesting observation can be developed by deduction. Hueper ba stated that there are about 35, 000 pereona espoeed in the United State*, sd we have found that the Canadian mine* employ about 8,000, Elsewhere, Ufca* been estimated that the workers In England who have espoeure total between 3* 000 and 5.000. With worker* la Africa, Seamark, Norway, and Uer countries, ax Uast 50, 000 persons must be espoeed throughout the world, ltd U can be assumed that this number has been fairly constant la tbe 20 year* Siact 1935 wbea the first ease of asbeatosis with lung cancer was reported. jU leest a million man-year* of esposure he* thus been accumulated, and IbU figure can be divided by the approximately ISO cases of lung cancer with liveliest* reported during the 20-year period. This gives a rat* of 15 per i;0.900 which t* at least Indicative that any lung cancer rate which can be dictated for worker* exposed to asbestos dust le no: rruck greater than that for the unexposed population. Comparison Dstwocn Eight Counties Adjacent to the Asbestos.Producing Areas iad right SMfCteri Counties______ To compare lung cancer mortality rates in the counties surround* ln| the atbestos.produclng areas with another group of counties in which ss asbestos miners are Ukoly to reside, the rates wors computed on the bests ol figures for the years 1950 through 1955. The eight counties selected fer comparison were *rgcatouil, Chatoaugay. Montnr.agny, Perineal, JUchlioe, Riv(ero*du~Loup. St. Hyacinths, and Torrebonne. mainly because they represent a wide geographic distribution throughout the Province. The eeualies selected because of their proximity to the asbestos mines Include Arthabaska, Seaueo, Drummond. Trontcnac, Megantic. Richmond, Sherbrooke, A' sad WoUe. Table )4 shows the number of lung cancer deaths for the years 1950 through 1955 for each of those counties, and a mortality rats, based on We adult mala population In 1952. To emphasise the comparison. Megantlc Ceuaty has boon shown separately, as has the Province of Cucbee and also the Province with the eight 'asbestos-producing" counties subtracted, Because f its unique lung cancer death rate, Montreal et Isle de Join* has also been listed in order to provide further comparison. iou s ir si 7M 9si ` i ooo*vtf ! p ii 0295 I* la apparent from the table that the lung cancer death rate for tbe eight esuatiea In.rr.ecUtelv surrounding the sebeetos.producmg area* is preeticaUy-ldentJcal with that of eight counties selected far comparison. White McgantU County has a rate early twice that of the combined eight elected.eeuatlee. It t lower than the rate for the Province, aed coaelderabiy lower than the rate for Montreal. The figure for Montreal would certainly he higher except for the very low numbers el death* reported for 1950 aad 1931. and it would appear that la those year# oome error la reporting bar . undoubtedly been made. On the heel* of the ether year*, 1950 aad 1951 death* would be expected to be about 100 greater. This would result in a rate of 40 per 100,000. The only poeelble conclusion from tbit comparison l* that ihero la ao evidence that the pereoae who live and work ia the counties surrouadiag aad adjacent to the aeheato*produeiag areas have aay greater Incidence of lung cancer than thoee who Uv elsewhere la the Previses. DtooMOst#wof All Recorded Lung Cancer Cases. Living and Peed. c'ffms??the Atbeetos Miners Although a simple enumeration of all the known or suspected cases c of cancer of the lung la those areas has ao particular value from a statistical point of view. It la of Interest to summarise such eaeet for the roeord, There were aloe death* prior to tbe beginning of the time period covered by the tudy. Includlog one in which the diagnosis was mediastinal lymphosarcoma. 47. Durlsgthe period covered by this investigation, there were nine proved cases end three suspected cnees la 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 Included such diagnoses as mediastinal lymphosarcoma, me** tholioma, cancer of the leg with msuitases to lung, obsess of lung, and cancer of the pancreas. One othsr was diagnosed.on the basis of x-ray only. In addition, thsrs are now living four, caste la which tbs diagnostic evidence Is strongly suggestive of lung caaesr. This is a total of 53 caeee of all types, Including ten "suspected" but unproved cases, and four that ars still living. The remaining 19 constitute the total of proved cases of cancer of the luag among tho asbestos miners sines 1940. The proved cases averaged 59 years of age at death, and varied between 37 years and 68 years. Their working span covered periods vary* lag from a minimum of 14 years to a maximum of 37 year*. Only three men bad Use than 25 yeara of employment in the Industry, Seven among those on whom ouch information Is available had a weighted exposure placing them in category HI, and tlx worked in an exposure represented by category I. Thors were only 17 among these proved luag cancer cases in which we have icformatlen regarding the presence of asbeetoeie. Asbestosl* was present in nine, although it was minimal la two. Two pathologists dtssgroed regarding Its presence la another. At least seven of the 19 proved lung cancers. Utarefera, were not accompanied by asbestosis. 0297 48. Summary anrt CaacLt'.cnt Interest la the question ot whether there may he aa aeeeeiatiea between lung cancer and exposure to asbestos has been evident since the report la 1935 by Lynch and Smith of a case la which lung cancer and ashes* losls were both present. As additional cases la which the two diseases eo aisled were reported, a causal association appears to have been gradually accepted by many authors, although aome workers considered the correlation to be inconclusive. The preeent study was commissioned in 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 cancers found In certain selected samples, such as cases coming to autopsy or death certificates in which aebeetoele was mentioned, It was apparent that they could not fulfill the requirements of an epidemiological and statistical Approach to the problem. The preeent study was, therefore, designed to mset the requirements of this method. After a preliminary survey to aplore the availability of reliable Information, data were gathered on workers la the asbestos mines In Cusbec, /fS yf 6**++ /* baaed on their medical records. A cohort was defined acswsiuli. j simrnfn # *;// x***s/- />*-t /wvrr * ** a- rrfrBmi-iiirt-wlW-tr-rr-n itii--tjii I \ 111111111 iiliel III ifm eimi> ,* W 44(. ^4 4 ts******/* ,*S Oata relative to their cbaraeteriotlce were collected end their status at the nd of a etx-year^erlod of observation was determined. In the case of those who had died, an exhaustive search of death certificates end Insurance records 029S V4i carried out in order to determine a* nearly as possible the exact cause of death. Mortality rates from lung caneor for the general population of the Province of Quebec and Its various counties and for the Dominion of Canada, ae well a* the United States were calculated from statistics collected In the appropriate placee. Comparisons of the rates obtained for asbestos workers and for the other population groups were made according to accopted statistical m sItinrls^rfi11 Vmm Vi snn nrplilnsrt fn i ims Aecords were obtained on 6091 pereont who fulfilled the criteria of the cohort. It was not poeelble to traee 133 of these for the whole period, bat 5771 of the remaining 5956 were found tn bo still living la 1955 or later. Of the It? known deed, cancer of the lung was considered to have been reason ably proved in nine and to be strongly suggested in three. The members of the cohort were studied with respect to age, length oi employment, a weighted average of their eapoeuro, and their smoking habUe, four thousand, six hundred and seventy-three were found to be smokers within the definition of that term ae used In this study. Thirty-four per.cent f the cohort were more than 45 year* of age, and 30% had been employed for longer than 20 yeers. Thirty per cent had a weighted exposure which plAced xrfa them \n category of highest exposure. The mortality rate for lung cancer, ae computed on the basis of nine "proved" deaths emoag the eohort was 25,3 per 100,000, When the three "Suspected" cases were added, the "tetel" rate for the cohort resets 33.8. so. The importance of the auepectod but unproved cases is determining those rate* has bees reiterated because U W likely that such cases would not be Included is the statistics tor tbs general population and because they influence the results so markedly. According to the findings is this.study. the mortality rat# from luag dancer doe# not appear to Increase with length of exposure or with degroo of exposure, a f%cawhich presents strong evidence against the eareisogeaiclty of asbestos. Comparison of the experience among the esbeetoa miners with that of various segments of the unexposed, comparable population shows that the observed number of deaths among the miners is not significantly greatar than the expected number. The rate for proved cases among the aebectce minors {25. J per 100,000) compares well with the rate of 22.5 per 100,000 lor the rest of the Province, and 20.8 par 100,000 for adult males throughout the Dominion of Canada. It also compares satisfactorily with rates of 3?,2, 25. J, and 21.0 obtained from various sources for adult males in the United Jutes, finally, in tble matter of comparison, U would appear that the world* wide experience of persona exposed to eebestos dust is not worse with respeet to lung cancer than that of the unexposed population. The counties surrounding the asbestos-producing erase, and In which it le presumed most of the asbestos miners Uve. have almost identical mor tality rates with those of eight counties widely scattered through the Province, end are tower then those for the remainder of the Province, and much lower than the rate for Montreal, 0 __,, -T' 51. Since 1940. there beve been 19 ceset la which the diagnosis of primary cancer of the lung may be considered to have bees proved. Approxi mately half of these case* were associated with asbeetosis. All but ose died (a the recogalted 'cancer-age'' and at least one-third had only the lightest exposure (category I) to asbeetoa dust. . On the basts of what are believed to be complete sad reliable data. It eecms fair to conclude that the eebestos miners In ths Province of Qsebee do not have a significantly higher death rate from lung cancer than do com parable segments of ths gsaoral population. Furthermore, the death rate from dung cancer la the areas contigu ous to the asbestos operations Is comparable to that in areae widely scattered throughout the Province of Quebec and Is lower than In some urbanised ereas within the Province. 0301 feibllorrap Uy 52. 1. Alatclo, hteobar A. Bronchial carcinoma; review of two hundred casts. J. Intern*;. Coll. Surgto&t. 26; 375-379, September, 1956. 2. AUen, M.L. Broncbiogenie carcinoma associated with pneumonocofuonUi report ol two caste, J. ladutt. Hyg, 16; 346-347, November, 1934. i* American Cancer Society, Inc. Cancer of the lung; *o evaluation oi the problem. Proceedings the Scientific Section, Annual Mooting, Nov. 3-4, 1953. American Cancer Society, Inc. Now York, 1956, 322 pp. 4. Anderson, C.S. and Diblo, J.H. Silicosis and careinoma of tbs lung. J. Hygnsn. 38: 185-204, March, 1933. 5. Baader, .\/ Aobestosls, Deutsche mod. Wochscbr. 65: 407408, March 17, 1939. f brent, W. experimental asbostosis. SchweU. Zttcbr. All*. / Path. U. Bakt. 14: 275-297, 1951. L Behrens, W. Jr. The clinic si picture and pathology of asbestos:*. 2. Unfallmed, u. Borufkrankh. 45: 129-140, June 15, 1952. K 8. Btrbllngcr, W. lncr<ate of lung cancer and diseases duo to dust inhalation. Med. Klin. 27; 1337-1342, September U, 1931. 9 Berenblum, 1. Irritation and carcinogens. Arch. Path. 38: 233244, October, 1944. 10. Bohme, & Atbvttotlt, Deutsche raed. Wocbschr. 62: 928-930, 1936. 0302 ....................... * V* 11. Bohme, A. Results. of periodical examination* of worker* In an asbestos factory. Bettr. a. SlUkose Forschung. 11: 34, 1951. 12. Bowles, O. Asbsstos.mllling, marketing end fabrication, U.S. Bur. Mine* inf. Clrc. Ho. 6269* 1*22, 1925. 12* Breslow, L*, Hoeglin, L., Rasmussen, G., and Abram*, H.K. Occupations and cigarette smoking aa factor* in lung caacar* Am. J. Pub. Health. 441 171-181, February, 1954. 14. Bristol, L.J. Roentgenologic aspects of aUicosia aod aabestoaia. A.M.A. Arch. Indust. tig. 11: 189*195. March. 1955. ' *46 4. T;y 15. Cartior, P. A contribution to tba study of aabestoaia. Arch. mal. profess. 10: 509*595. 1949. 16. Cartier. P. * Discussion on esbestoei* cancer of tha lung. A.M.A. Arch. Induet. H/g, U Occup, Med. 5: 262-262* T953^ ||j ^ 17. Cartier* P. Some clinical observations of asbostosis in mine and mill workers. A.M.A. Arcb. Indust. Health, lit 204*207, 1955. , It* Clorons. J. Research late pulmooary asbostosis in Belgium. Arcb. Beiges Mod. Socials. Hyg., Med. du Travail and Legale. It 557*545* November* 1951* 19* Ctynee. AebeelusU and silUnsU. Brit. Med. 2* It 279* 1921*. 20. Coffin* C.J., Duryoo, H.C.* Meier, II.C., Pardee. H..0* and Vfyntor* E.L. The effects of tobaeco smoking. Panel Meeting. Dull. Now York Acad. Med. 22: 122*156, February, 1956. 21. Cohart, .M. Lung cancer and economic status. Caacsr. $; 1124*1129. Hovember-Deesmber. 1965. 22. Cooks, W,. Pulmonary ssbestooli*. Brit. Med. J* 2i 1024* 102S, December 3, 1927. 54. 23. Curoton, R.J.R. Squamous cell carcinoma occurring in ashes* tosls oi tbs lung. Brit. 3. Caneor. 2i 249*253, September, 1942. 24* Cutler, 6, J. SchneLderman, U.A., and Greenhouse, S.W. Some statistical consideration In the study of eoncor in industry. Am. J. Pub. Health. 44: 1159*1166, September, 1934. 25. Daviss, D. F. Currant status of lung caneor research! some pathogoectic aspects. Ca, American Cancer Society, Inc. 4: 149*174, September, 1954. 26. Deomeuleo, R., Rousseau. L,. Giroux, 24., and Sirois, A. Amiantose et cancers pulmonaires. domains de. hop, Paris. 23 (Jj 1820*1823, August 7, 1947. 27, Doll, R. Bronchial carcinoma; incidence and aetiology {Milroy lectures, abridged). Drit. Med. J. 2t 521*527, September 5, 1933; $55*590, September 12, 1953. 26. Doll. R. Mortality from lung cancer among asbestos workers. Brit. J, Induet. Med. 12: *1*86, 1955. 29, Donnelly, J. Pulmonary asbsstosis. Am. 3* Pub. Health. 23: 1275.1261, December. 1933. 30. Dorn, U.F., and Cutler, S.J. Morbidity from cancel in the United States. Pub. Health Monograph No. 29. P. II. S. Publication No. 416. Washington. U.S. Government Printing Office. 1955. 121 pp. 31. Dorn, H.F. Cancer morbidity surveys! a tool for testing theortee of cancer etiology. Am. 3. Pub. Health. 45: 615*421. May, 1955. 0304 vl. 32. gbcrt, D.S., And Geiger, A.J, Pulmonary aebesteeis *nd carcinoma; report of a cast with necropsy findings. Am. Rev. Tubcrc. 34: 143*150, July, 1935. 55. 33. llman, P. Pulmonary aabestoeis; Us clinical radiological, end pathological feature# end Associated risk of tuberculosis iA* lection. J. ladust. Hyg. 15: 165*153, July, 1933, 34, Umaa, P. Pulmonary asbestos!*. Proc. Roy. See. Med. 34: . 557, July, 1941. 35. Fell, A, Pneumoconiosis in asbestos workers. Press* mod. 39: 1872*1874, December 19, 1931. 36. Pulton, W.B., Dooley, A., Matthews, J.L,, and Houts, R.L. Asbsstosis. Part ill. The effect# of exposure to dust an* . countered in asbestos fabricating plants on the health of a group of workers. Special Bull, No, 42, Penn. Dept, ef Labor and Industry. Bur. of ladust. Standards, September 20, 1935. 37. Gardner, L. U., and Cummings, D., Studies on experimental paeumoeoaloeis) inhalation of asbestos dust; its effeet upon primary tuberculous infection. J. ladust, Hyg. 13; 65*61, February; $7, March, 2931. 36* Gilliam, A.C. Mortality trends In lung cancer. Caaeer. 6; 1130*1236, November*Deeember, 1955. 39* Gilliam, A.G. Mortality attributed to lung cancer In the large cltiee of the United State* In 1948 and 1949. J. Nat. Cancer last. 15: 4307*1312, 1955. 40. Gloyne, S.ft. Two eases of squemou# carcinoma of the lung occurring in aabestoeis. Tuberel. 17; 5*10, October, 1935. 41. Gloyne, S.Jt. Pneumoeoaloole; a histologies! survey of necropsy material in 1205 eases. Lancet. 2; 810*814, April 14, 1951. CPOS 42. Gloywe, S.H. A c*oe of oat*cell carcinoma of the lung occurring in aebestocis. Tubercle. lot 100*101, December, 1916. 4). Gloyno, 3.P., and Merewetbcr, .R.A. Aebettoe. Occupation and Health, Supplement to Encyclopedia on Occupation and Health. Geneva, Internet, Lab. Office, 1938. 44, Goldblatt, M.W., and Goldblatt, J, Industrial carcinogenesis and toxicology. Edited by E.R. A. Mefewetber. Induet. Med. L Hyg. 3: 185*188. 1956. London, Butterworth k Co., Ltd. 45. Haensaoi, V.M. Epidemiological teite of theories on lung cancer etiology. Pub. Health Hep* 71; 163*172, February, 1956. 46, Hammond, . C, Lung cancer and common inbalante. Cancer. 7; 1100*1108, November, 1954.. 47, Hammond, . C. Etiology of bronchiogenic carcinoma. Ca, American Cancer society, Inc. 6; 156*168,.September, 1956. . 46, HoUcb, H.B., and Angrlat, A. Bronchiogenie carcinoma in > : aeeoclation with pulmonary asboetoeie; report of two caeos. Am. J. Path. 16t 123-135, January, 1942. 49* Homburgrr, F. The coincidence of primary carcinoma of lunge ' and pulmonary aebeetoele; analytie of literature and report of two caeee. Am. J. Path. 19: 797-807, September, 1943. SO. Horn. D. le lung cuneer on the increase? Evaluation of preeent day evidence. Cancer of the lung. Proceedings of the Scientific Section, Annual Meeting, Nov. 3-4, 1953. American Cancer Society, Inc. 51. Koroig, F. Clinical coneidcrationa on the ^ueetion of industrial cancer of asbeeto# workers. 2tcehr, f. ttrebsforsch. 47; 281-287, 2938. 0306 $7. 92. Hueper, V/.C. Cancer in lit relation to occupation and environ ment. Dull. Am. Soc. Control Cancer. 25: 63*69, June. 1945. $5. Hueper. W.C. Significance of induetrial cancer La the problem f cancer. Occup, Mod. 2i 190-200, September, 1946. 94. Hueper, W.C. ataviroemental and occupational cancer. Pub. Health. Supplement 209. Washington. D. C.. 1949. 69 pp. 99, Hueper, W.C. A methodology for environmental and occupational cancer eurveye. Pub. Health Monograph Ho. 1. P.H.S. PublicatiOA Ho. 12. Waeblngtoa, U.S. Government Printing Office. 1990. 96. Hueper. W.C. Environmental lung cancer. Induct. Med. and Surf. 20t 49*62, February, 1951. 97. Hueper, W.C. Occupational and environmental pulmonary cancere with epedal reference to pneumoconloeie. Procecdinge, 7th Saranac Sympoelum on Fneumoccnioeie. 1952, 59. Hucpor, W.C. A quect into the environmental cauoee of eencer Of the lung* Pub. Health Monograph No. 26. P.H.S. Publication No, 492, Waehington, U.S. Government Printong Office, 1995. 99* Hueper, W.C. hovironmeatal caueee of caneer of the lung other Shoo tobacco emoke. Ota. Cheet. 20: 141*159, Auguet, 1956. 40, Seeelbachar, it, 3. , Xlaue, H., and Hardy* H,L. Aebeetoele and bronchfopenle eareinomai report of one autopeied cate and review of available literature. Am. J. Mod. 19: 721*722, November, 1952. 41, Kennaway, .L*t and Kennawey, N.M. A etudy of the incidence of cancer of the lung and larynx. J. Hygiene. 26: 226*267, June, 1936. 42* Keanatvay, .L., arc! Ktnnaw&y, K.M. Studies of incidence of cancer cI the lung and larynx. Brit, J. Cancer. 5: 153-155. Juno, 1951. 58. 62. KJot*, M.O. Aaaociation of ailicoai* aad carcinoma of the lung. Am, J. Cancer. 35: 38**9, January, 1949. 64, Lenta, A. J., McConnell, W.J., and Fehnel, J. W, The effect* of the inhalation of aabeatos duet on the luog* of aebeatoe worker*; preliminary atudy. Pub. Health Hep. 20: 1*12, January 4, 1932. 25. Lenta, A.J. Sillcoele and aebeetoeie. New York, London, Oxford Unlverelty Preaa, 1938. 39 pp. 66. Low, .A. Uee of life ineurance company record* for eancer etudiee. A.M.A. Arch, iaduit. Hyg. $: 198*203, March, 1922. A < ^(4^)' 67. Lintbacb, A.J., and Wedlcr, H. W. Occupational cancer among aabeetoe worker*. Virehow* Arch, f, path. Aaat. 307: 387*409, 194). 68. Lynch, K.M., and Smith, W.A. Pulmonary aebeetoeie} carcinoma of lung in aabeato.aiJicoal*. Am. J. Cancer. 24: 26*6*, May, 1938. 69, Lynch, K.M., and Smith, W.A. Pulmonary aabeatoaia; a report of bronchial carcinoma aad epithelial mouplaaia. Am. J. Cancer. 34; 547.273, Auguet. 1939. 70. Lynch, K.M. and Cannon, W.M, Aebecteeiej analytic of forty necropaied caeee. Ole. Cheat. 14: 874*889, November*December, 1948. 71. McPbeetera. $. B. A aurvey of a group of employee* eapoaed to aebottoe duet. J. Induat, Hyg. aad Toxicol. 18: 229*239. April, 1936. 'M . # 72. Mte-*ther, .ft.A. The oceurrt'.ie* of pulmonary fibroia aod other pulmonary affection* tnaabeatoa worker*. 2. Induat. Hyg. 12: 198, May: 229. Jua. 1920. 72. Merewether, C.R.A., end Price. C.W. Report oa effect* of aebesto* duet on the lung* end duet euppreeeioa in the atbeito* lnduetry. London, K.M.S.O., 1920. 74, Mereu-etber-.-E.'R.A. ..Ajaomarenduni a 4*b*toi*. Tubercle. 15:'69*80, November,- 1922;' 109, December, 1922} 15: 1S2, January, 19J4,"*--'n-- '' 73, Mcreviather, fi.R.A, AnnuAl report* of the chief inspector of fectoriee. London, H.M.5.O., 1947. 76. Werewether, .R.A. Induetrial medicine end hygiene. 2t London, ` Lutterworth h Co., Ltd., 1956. 617 pp. 77. Nordmaan, M. The induetriel cancer of worker* in eabetio*, Zicchr. f. Krebeforcb. 47; 288*202, 1938. 78. Nordmana, M., and Sorgo, A. Pulmonary cancer produced by aebeetoe duet in experimental animal*. Zuchr. f. Krebeforeh. 51 168*182, 1941. 79. Phillip*, A.J. Mortality from canecr of the lung in Canada (1921*1952). Caned. Mod. A. J. 71: 242*244, September, 1954. 80, Saupe, . further contribution* to the roentgenological diagno*is of avbeetoel*. Arch. f. Cewerbepetb. u. Ceworbehyg. 9; 291* 406, 1929. 81. Smith, K.W. Pulmonary disability Li abe*toe worker*. A.M.A. Arch. Indue*. H73. 12: 196*202, August, 1955. 0?Q> 02. Smith, L.W. Pcnumoconioei* and lung eaneer with epecial re* fercnce to eilicoeie and eebeetoei*. Compens, Med. i: 3*10, November, 1949. 83, Smith, W,E. Survey of tom* currant British and European tudioa of occupational tumor problem*. Part 111, Asbestos. A.M.A, Areh. laduot. Hyg. 8: 242*283, March, 1982, .A 84, Stoll, R., Base, R, and Angrist-, A, Asbeetoeio associated with bronchiogeoic carcinoma, A.M.A. Arch, lot. Mod, 82: 831* 834, December, 1981, 88, Teleky, L, Cor borufllcho iungonkroba, Acta Ualo latornat. Contra Cancrum, Pario. 3: 253*273, 1938, Aloe, Zeatr, Coworbchyg. Unfallverhut. 27: 33, 1940. 8b, Vorwald, A.J., Durban, T.M., and Pratt, P. C, Experimental etudiee of aabestosie. A.M.A. Areh. laduot. Hyg. 3: 1*42, January, 1981. \ f?i%t*v 87, Wedler, H.W. Aobeotooo und lusgenkrobo. Doutaehe mod. Wochocbr. 89$ 578*878, Auguot 6, 1943. 88, Wogclluo, C. Changes in tho lunge in 128 eaaoe of asbeetoeia oboorvod in Finland, Acta rediol, 28: 139*152, 1947, 89, Worber, M. Pulmonary oebeetooie associated with carcinoma. 2ontralbl, Arbeitoaed. u. Arboitoocbuta, 2: 179*180, November, 1952. 90, Wood, W.B., and Cloyna, S.R. Pulmonary aabeatoola complicated by pulmonary tuberculosis. Eancot. 2: 954*956, Octobsr 31, 1931. 91. Wyars, H. Aabasteais* postgrad. M. J, 25: 631*638, Dscamber, 1949. 92. Wyndsr, C.L., and Crabam, E.A. Etlologic factors la bronckiegenic carcinoma with special reference te Inluetrlal exposures; report of eight hundred fifty*eeven proved cases. A.M.A. Arch, ladust. Hyg. > 4: 221*235, September, 1951. /-