Document YDNbjMRpMwD4MLZkdyRmn61On

PLAINTIFF'S EXHIBIT An epidemiological Study of Lung Cancer in Asbestos Miners DANIEL C. BRAUN, M.O., and T. DAVID TRUAN, M.A., Pittsburgh ! Ku-r -incc tilt- pronounced increa-c in sht- incidence nt lung i"inivi' among males became appnrenl. there have been aUempls to associate it with one or another of the various elements in the environment of man. 1'lie approach used by some workers has been to .-uspivi one or several sttb-tanees and then -cl abnu in an intensive -can'll for Unis' eiineer aiiioii.tr 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 dialogic conditions, has been to emphasize the percentage relationship in extremely small Series of cases, with control cases which are not in tiny way comparable." It would seem inevitable that asbestos should come under scrutiny in this manner, because prolonged exposure to this material is known to cause a specific type of pneu moconiosis. and because persons who show this form of pneumoconiosis often come to autopsy and provide a ready source of material for study. It was in this way that reports of the simultaneous occurrence of limy cancer and a.'bestosis began to accu mulate after the report of a case by Lynch and Smith ** in 1935. Within the next It) years, about 15 additional cases were re ported. and in 11 >5-4 Mercwether 70 reviewed all deaths from asbestosis recorded in Eng land since March. 1924. Lung cancer oc curred in 16G of these cases. Giovne.41 Accepted fur publication Jan. 20. 10SS. 1 his study was made possible through a grant irmn '.he Quebec .Asbestos Mining' .AsmviaIion. Medical Director i Dr. Rrann) and Statistical Consultant (Mr. Truant. Industrial Hygiene t-'ouud.v.ion. whose work t- also IrotUeiilh referred toi as establishing a connection between asbes-i tosis and cancer of ilu- iung. reported in' l`>51 that cancer of the lung was present, in 14.Kf of ashestosis cases examined by him. In 1941. Xordmanu and Surge7' claimed to have produced lung cancer in mice which tl'ev expo-cd ad'edits dust. Since 1951. additional ca-es of cancer ot the lung coexisting with a.-bc-to-is have been reported, and. according to Iluepei""' about 100 such i'.im-- had been reported up to 1955. A< a result, an association lietwven the. two diseases appears to have been ac cepted by many authors, and several writerwere using the term "ashe-'.osis cancer" of tile lung. Werlier.''* in 1''52, stated cate gorically that in 7G to 17'} of eases of asbestosis. after a latent period of about 1 to 2d years, carcinoma becomes estab tished in the lung. On the other hand, not all authors in cepted this alleged association without reservation. Saupein 1939 reported that he had discovered tin ca-es of lung cancer among 620 cases of asbestosis which he had examined: and in 1942. llolleb and Angrist4S expressed the opinion that the number of eases of asbestosis with lung cancer was too small for statistical evalua tion. In 1947. Wegelitts '1- reported 126 radiologically diagno-ed cases of asbestosis among 476 worker- in Finland, and found no cases of lung cancer in this group. Goldblatt and Goldblatt in their section of Mercwethers latest hook,'14 state: "Hut a( 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 ASARCO ELP 0002835 r. \. i * lUNG CANCER IN ASBESTOS MINERS i-nrni rwr VTt^TCTSfiSag^^ i no reliable criterion by which one can nticipate. carcinogenicity, and, as is well nown, relatively minute changes in the tructure of a chemical carcinogen are suffiient to diminish or eliminate carcinogenic ction. If asbestos is indeed to be regarded as a arcinogen, the need is felt to demonstrate ome property which can be regarded as nmething more than inertness." These authors advance the theory that, ntil some more experimental evidence of irect carcinogenesis by asbestos or a deomposition product of it can be obtained, sbestos might be considered as a "co-carinogen" which only induces a further deelopment of a preneoplastic condition rought about by something independent of he asbestos, such a- an endogenous factor. Thus the literature, while tending to supon the thesis that asbestosis is in some rav related to the development of lung ancer. is by no means unanimous. Alto;ether. it is perhaps more confusing than ^lightening. A careful review shows that he majority of the reports are clinical and tot epidemiological. They lack many elenents necessary for the application of pidemiolugical techniques to their content, jid most of the authors do not make claim 0 having done sn. What has happened is hat succeeding authors have drawn concluions and generalized beyond the scope of he works which they- quote. Nowhere, for ixainple. have we found references to a *ofiliation of asbestos workers, although evernl authors who have quoted the oberved incidence of lung cancer in autopsies 1/ persons zoho also had ash,stasis imply hat this incidence applies to asbestos work s. generally. We have likewise been 1 table to find any study which actually tilculated the incidence of lung cancer along a population of persons who had isbestosis, and not iu>t those who came to tutopsy. With the exception of a paper ty Doll,28 none of those reviewed gave any lata on exposure and dust concentrations, nd even Doll's paper merely mentions "scheduled" areas, by which is meant, "those areas where processes -are carried on which were scheduled under the Asbestos Industry Regulations of 1931 as being dusty." There is, furthermore, a complete lack of definition of terms as used in the pub lished literature. For example, the term "asbestosis," as used, may refer to changes observable only by microscopic examination of the lung tissue, or it may mean a radiologically detectable condition. Most of the published reports obviously included women among their cases, but some of them do not give the number or proportion of women involved in the study. There is also a lack of uniformity's to what type of exposure most studies have dealt with. Of 99 cases enumerated by Elucpcr in 1955. only 10 appear to have originated in the United States, and 7 in Canada. Some of the earlier reports ap parently included asbestos miners, but it can be .assumed, since 82 of the 99 cases had originated in Kngland, and since no asbestos mining operations are carried on in that country, that most of the reported cases have involved workers in the textile or fabricating industries. Such factors as smoking habits, family history of cancer, length of time in the industry, and age of the individual case arc also notably absent in the majority of these reports. With this understanding of the limita tions of the existing literature with respect to epidemiological generalization, it may be of value to consider in somewhat more de tail some representative earlier publications, a few of which were referred to briefly above. J One of the most detailed studies and one which deserves the most serious considera tion is that reported by Doll28 in 1955. This study reviews causes of death among asbestos workers based on coroners' rec ords. It also attempts to estimate the risk by studying records of men who worked for at least 20 years in exposed situations. raun--Truatt 6.55 ASARCO ELP 0002836 A. if. A. ARCHlTEA OE IXPCSTRIAL HEALTH Doll concluded that lung cancer was a spe lung cancer in other forms of pneumoconio cific industrial hazard of certain asbestos sis was 6.7%, anti in 169 cases which workers and that, after 20 years of expo proved not to have any type of pneumo sure, the risk is 10 times as great as for coniosis it was 8.3%. Gloyne considered the general population. "the mortality of the asbestos workers" to This article is important for several rea be "disturbing." First of all, it is obvious sons, in addition to the definite conclusions that the paper does util deal with the "mor at which it arrives. lror example, it begins tality of asbestos workers." and secondly, by stating that "in view of the infrequency it must be borne in mind that all of Dr. of asbestosis, this large number of cases Gloyne's cases were submitted to him for (61 cases of lung cancer) suggests--but study because the findings were unusual does not prove --that lung cancer is an for uncomplicated pneumoconiosis. It can occupational hazard of asbestos workers." reasonably be assumed that cases, including Neither this article nor any previous one those of asbestosis. in which the findings which we have examined presents any fig were not considered unusual were not sent ures to prove that asbestosis is an infre to Dr. Gloyne for examination. As a mat quent occurrence. Estimates of the number ter of fact, in the same paragraph in which of persons potentially exposed to asbestos he expresses concern over the incidence dust in the United States alone van' from rate in asbestosis, Dr. Gloyne himself 10,000 to 35,000. and the incidence of as points out that the rate for lung cancer bestosis of any degree might be higher than based on necropsies at the London Chest] Doll imagines. Hospital was 21.3%. while the figures of) This study, like so many others, involves autopsy records. The number of persons involved in the statistical analysis is only 113, representing only 1,042.25 man-years of life. It is also true that in selecting men who had been employed for at least 20 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 1951 Gloyne41 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 the Registrar-General showed only 2.4%] He thus recognized that autopsies on a cer-! tain selected group of cases were not rep-! resentative of the general population. It would seem. then, that notwithstanding the. value of Dr. Gloyne's work, its importance] as an index of the prevalence of lung earn cer in asbestotics has been misinterpreted by some who have quoted him. All that it really shows is the fact that in a group o 121 cases, selected for special study pri marily because they seemed abnormal by, preliminary examination, 17, or 14.1%, had lung cancer. Merewether 75 in 1947. in the report of the Chief Inspector of Factories, reviewed all cases reported between 1924 and 1946 in which asbestosis was the cause of death or a coexisting condition. This work was later extended to include all such cases re ported up to December, 1954, by which time there were 344 deaths, including 205 males incidence rate of 14.1% for lung cancer and 139 females. Among them were 55 among asbestosis cases coming to autopsy. cases (16%) of cancer of the lung, 41 in There were in his series 796 cases with sili males and 14 in females. It is quite possible cosis. and 6.9% of these also showed pri that a large number of asbestotics who did mary cancer of the lung. The incidence of not die of their asbestosis, or in whose 636 Cot. IT, June. 1951 ASARCO ELP 0002837 death certificate it was not mentioned, may have been missed. The import of this 16l/c is enhanced by * lie simultaneous statement that the incidence "t lung cancer in autopsies of the general population is .only I^c. The danger of attempting to compare a rate found in 544 ca-es with the r;ite for ihe general [lopulalion without respect to age. occupation, and many other variables, such as smoking habits, is obv.ous. Lynch.70 who with Smith1'" had reported the first case in l'*.i5. reported 4 cases of carcinoma of the lung in a series of 49 autopsies mi workers in an asbestos manu facturing plant who were shown to have "demonstrable deposits of asbestos in the lungs." This, of cut'-e. is not necessarily identical with the li-a'isi: asbestosis. Lynch, himself, [joints nut that, .although this is an incidence of 8.5'<. "both figures are too small for very serious statistical types of :alcula*ion." Nevertheless, later writers have used this paper to strengthen the case for ati association of carcinoma of the lung with asbestosis. It is also ot interest that Ivlotz03 found only the same number of rases of lung cancer in a series nearly 10 rimes as large, i. . 4 in 47.4 cases of isbestosis. Behrens. a> cited by Merewet her.7'1 estinated that, of 5<)') cases of asbestosis `ln the iterature. 44 showed associated cancer of he lung-- giving an incidence of 14.2'?.. 1`his i> an illustr.r.'oir of generalizing an ncidence obtained hi a group of cases' vhich were undoubtedly reported only /vrtK.vr some i.f th. in -bowed lung cancer, to mssihly hundred- of asbc-totics whose vises were mver reported. The same apilies to the conclusion of Teleky,'7' who ippears to have reviewed reports of 59 uitopsivs on persons with asbestosis among vhich 6 case.- of lung cancer occurred. InWmalinn from si.urces such as thc-e does tot justify generaii/ations with regard to tiortality rates. I'erhaps no mu has written so extenively on the 'iibieit as litis I f neper.7,2 1955 he reviewed the c.i-es-'" reported prior to that date and enumerated a total of 99. Eleven of these were those dis cussed by Doll 28 and may have been cases covered by other authors. Eight were dis covered by Kennaway and Kentiavvay82 in art analysis of death certificates, and, unless Merevvether's study was incomplete, these cases should have been included in his re port. Of the remaining 80, it is quite pos sible that the 31 contributed by Mercwcther and the 17 by (iloyne contain some duplica tion with each other or with those of other English authors. Principles of the Epidemiological Method Dorn '1" has pointed out that much of what is now thought to lie pertinent concerning the comparative frequency of lung cancer in different imputation groups has been de veloped from the analysis of clinical ma terial, particularly surgical anil autopsy record-., supplemented t<* some extent by the reported impressions of various clini cians based upon their personal observa tions. More recently, however, attention has turned to the systematic investiga tion of this problem iv the same methods that have proved so successful previously in the study of communicable diseases, that is to say. by epidemiological methods. In order !o apply this method of investi gation to the problem under discussion, vve were of the opinion that a study should be planned as to provide t 1 ) a well-defined population group: i2) available data for all members of this population, including the healthy as well a> the ill: i3) a sample which is truly representative of the popula tion: (41 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 die group seems to have liecn available to the author. In order to draw a generalization regarding all asbestos workers, it i.- necessary for a study to in clude living persons as well .is the dead. \raun--Tru.ln 637 i ASARCO ELP 0002838 -/. H. ARCH/l IS at- IXIiC.srRIAl. lth.AI.TH Limiting the investigation to vases 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 asliestos miners ex|<erieiice 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 seem' ad\isable to discu-s the differ ences Urtween the epidemiological approach and lhar used in the 'indies which have lieeii reported to date A very important coii'ideration is the fact that lung cancer, m spite of its increasing number', 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: f 2) comparing the relative frequency of cancer in a group of hospital ized patients: 131 comparing the relative frequence .of cancer in a group of cases coming to autopsy. Attempting to compare two population groups, looking only at the relative fre quency of cancer in various body sites, may result in finding a higher percentage i relative frequency i in one of the groups, when, in fact, the mortality rate of cancer of a particular organ is exactly the same in 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 autopsv 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 size, hut 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 i<> make proper comparisons and to draw only those conclusions which are valid and justified. A good statistical 'Indy of cases of cancer of the lung occur ring in a group of -iiitop-ai-s can load to a proper inference concerning the frequency of lung cancer among cases coming to autopsy, but only to such cases. Fur 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. j There is some danger that the figures; reported bv some authors may be niiscon-l strued as applying to asbestos workers ori 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 asbestos miners has been estab lished in such a way that it constitutes a good sample of the whole population of asbestos miners in Quebec. Data for all members of this group have been collected and analyzed. Those concerning lung can cer have received most careful considera tion. Details of the methods employed will be set forth later, but the type of approach is considered to permit of fair comparisons and valid generalizations. Collection and Analysis of Data A preliminary survey of potential sources of information in February, 1956, involved 6.18 I'ol. 17. June. IVfil I ASARCO ELP 0002839 t.VXC CAXCER IX ASBESTOS MIXERS discussions with the physicians in charge pf the asbestos companies' programs and frith clinicians, pathologists, representatives pf City and Provincial health departments nd of the Canadian Cancer Society, and Pther interested persons. It was found that morbidity data, although somewhat limited, frere available from such sources, as the jospitals in Montreal and Quebec City, and he 13 cancer detection centers in the Prov ince. However, because of the high nmrJalitv in lung cancer, it seemed advisable }o depend upon data relating to deaths. These we found to lie obtainable at the t'ital statistics department of the Ministry >t Health in Quebec Cite. From the preiimi.nary survey, it was ap'parent that exteniive and detailed information could be fathered with respect to both the persons jmployed in the asbestos mining industry md the mortality figures for the general sopulation. Following this exploratory survey, the iiitial effort was directed to the collection if data relating to all workers who had Jeen processed through the clinic at TlielJord Mines since its inception in lf,47. and similar' information regarding all workers It A-l>e-i< >s. Qtic. Data from the clinical ecords included the age. family and porlotial medical hi-tories. smoking habits, lumber of year.- of exposure, an estimate jf weighted expo-lire, ami the course of be individual'- health -tatus or the cau.-e jf his death. ! From thi- information it was possible > formulate a "c.-hori" wliicli could be well efined. .-houlil he representative of the hole group, and could he followed for a efitiitc period of time. All of the available xperienoe indicates that the development jf asbesto-is in less than five years of exosure must be somewhat rare. Acoordiglv. the cohort was defined as including very miner who had a total exposure of ve or more years, and who was cm the nployment roll.- in 1050. Office and other onexposed personnel, regardless of length f employment, were not included. This ' cohort was then followed by means of the annual 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 to the physical examination results and x-ray findings at the end of the period. .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. Thc-y represent men who had left employ ment through retirement or resignation. Kvenutallv. all but a small number of these were accounted for as either living or dead, and in the latter event, the cause of death was substantiated in a similar manner, and the results added to the original list of deaths. Death certificates for the Province of Quebec for the years 1952 to 1955, inclu sive, were reviewed in the department of vital statistics of the Provincial Health Ministry, together with statistical sum maries of the causes of deaths in the Prov ince by counties. All cases in which death was certified as having been due to pri mary cancer of the lung were examined for such information as place of residence, occupation, date of death, hospital in which death occurred, and whether or ttot an autopsy was performed. Cases in which lung cancer was given as a cause of death, but in which it was nut specified as to whether the cancer originated in the lung, were also reviewed in an effort to include all instances of primary carcinoma of the lung in the study. The stati-ties for the Province of Quebec relate to imputation, 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. r,mn--Trmn Ai<> ASARCO ELP 0002840 if. A. ARCHlTHU OR 1XDCSTRIAL HEALTH 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 hv a group policy of life insur ance which, fortunately, nearly all of then: continue to carry when they retire. A very few tire 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 Miiall number. A? 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 caneer of the lung. Deaths from lung eancer 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. The deaths were then verified individually by 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 caneer of the lung is con sidered to have been proved as the cause of death. A few cases in which lung cancer is strongly suspected but not proved as the cause of death were considered separately. Mortality rates have liven calculated using both the "proved" and the total of "proved" and "suspected" cases during the years un der observation. Comparisons were then made between the death rates from the same cause among specific segments of unexposed persons. All lung eancer 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 every case diagnosed hut 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 asliestos-produeing counties has been made with that in counties which are far removed from the ashe-tos mine'1 and in which, presumably, no a-botu': 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 tno'-t 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 generat population. Description of the cohort will be presented here as a preface to the results of the study: Original Cohort Io--t Person* Deducted Final Cohort Living in 1955 (working and retired) Dead hy 1955 Cancer of him: Questionable cancer of lung Other causes Vnkno^n causes Smokers Nonsmokers t'nknown 0,091 13 J 5.95S 5,771 187 < 16< < 4,67: 1,26; 2( Tables 1. 2. 3. and 4 present age, number of years of employment, weighted average exposure, and smoking habits of the cohort A comparison of the exposure to asbesto: dust is presented in Table 3. All member: of the cohort were placed in one of three categories, representing increasing degree: of exposure based on a weighted average of the years spent at various levels o: dustiness. The degree of dustiness for eacl job category was eletermineel after consulta tion with persons familiar with the environ ment and conditions in the various worl 640 Vat. 17, June. 195. ASARCO ELP 000284-1 LUNG CANCER IX ASBESTOS MIXERS Table 1.--Xumber and Percentage Distribution Table 2.--Number and Percentage Distribution by i by Age _____ Length of Employment Ape 20-44.................................... .............. .............. .. 65+ ................................. . ... .............. Totals.................... ............ Averse Ape..................... ....... Xumber 3.001 1,124 615 315 3 5,95s It * Loss than 0-5%. Per Cent 06 ly 10 5 * 100 Length of Employment 5-9................................................... 10-19................................................ ._ 20-29.............................................. .. 30-39................................................ . 4<M9................................................ . 50+................................................ Totals................................. Average years of employment....... Number 1,793 2.396 922 603 165 55 5,958 18 Per Cent 30 40 16 10 3 1 100 areas. I'or the purposes of calculation, the assumption has been made that the relation ship between these categories is linear, and that Category 11 i> twice as dusty, and Category III three times as dusty as Cate gory- I. ually smoking more than five cigarettes per day. Persons who smoke pipes or cigars exclusively were not considered to be smok ers for the purpose of this study. Table 5 presents the vear-by-year ex perience of the cohort and indicates the Table }.--Xumber and Percentage Dislrihutbm by Iixposurc Category Tabi.e 4.--Number and Percentage Distribution by Smoking Habits Exposure Category Itl1lf....................................................................... Vnknown ........................ Totals.............................. Average Exposure....................... Less iban 0.5%. Xumltfr 2,031 2.150 1.772 5 3.95R 2.0 pt root 34 3*' ,w too Smoking Habits Smokers.................. Nonsmokers........ I'uknown..... Totals............... .... ............ Less Ilian 0 Nun: her 673 1.265 20 Per Cent 79 21 100 The fourth variable. ,-moking habit>. was similarly tabulated and! is shown in Tabic 4. This wa- included 1 itoaii'c* the information'ua- available and becau-e smoking was regarded a.- -me <>f the variables which, beside- the environment, could conceivably influence the development of lung cancer. As used in this 'presentation, the term smoker refers to a cigarette -moker. habit- number of deaths each year from specified causes. In general, a case \va> considered to be "proved" a- one of primarv cancer of the lung when the records showed that the diagnosis had been -upported by an autopsy or >urgical resection of the lung with micro-copic examination of the re moved tissue, lit otu- case so considered, however, diagnosis was confirmed by broti- Tvbi.e 5.-- -IVtrr lixft'ricuc of Cohort and Death Rates per tul'tiQQ Man-) ears of Risk Cause * t Death ear MO.. ........... Mml...... ...................... ..................... M3... M4... 335... ........................ N\ Ahve At Recummc f \ ear -V.M2 S.'iSi 5.6 in Pn>vel Primary Ca. ol Lung l j 0 2 1 3 Su<i*ected Primarv Ca.of Luni* 2 0 n 1 it i* oilier 12 17 37 34 :a :t: Totals.................. ...................... 9 3 toy Proved** tuv per hXt.000 man-y ar< of ro k-S533--"* Total 'rute per 1C0.0C0 of ri.-k J1,2 r-*3I.O Unknown 1 1 0 ) 4 n i> Man*Years of Risk 5,950 5h.:9m32.u 5 v*u 5.790..'. 35.271.5 iraun--Truan 641 ASARCO ELP 0002842 ./ 1/ .f .//v-t /////> // /.\"< 'V.v/.// iih.ti in '1 \m < *': v*;.* ' t \isrj ,-r J'riuniry' C oui't r #/ */ l.U*Ut \tf. IVt \ "C* W*K> SV- Y\* 'll Y-* Y** iS > m\ ii. i\n. 11 \\ vr. Ui i t: in Cn. 1 j -j;r mCni.II j:i>r ui<\tt Ul yr, ;a C-ii. 11 \t m (* * I > yr. m c.\,i. 1(1 X* ii ,V* : a -v. -51 i :i i y * 5M v- V-* V*4 v* Y-YrY.jY.. Mfiiti-a Y- Y-Y^ \N..* \'i. 1 \ 1 >u:i!i/:ann ..i.ii ! another. although there was in* .msi)~y. the diaguc-i- i'if jirimary nf the lung -edits i> ll.lM: 1 il-<-I J ! (.< >M< I i|lll>tl'>tl. Thi t'-nn "'a-i.iilci'' {r*,,:.n'v i.meer nf the Hull; w.c |>jritc-e in v Inch tlu- diagnc-i- remains m dn"I*t hut -uuse cl the evidence poml- lu i/aiinT et the lung. There were tliivo -m h ease-" Thi; term "man nai'- nf :a-k" ha- hcvtt used i" mean the nui-.licr i*i* men at ri-k icr the year under .ii:il: -si A pvtsuti vhu Ii-1-*I th:nagh**tl! 'In- veer n;i> ceuntcd a.- ,i lull mau-ve.e. vid. ii*:i *ii'.c whn died lurin'; the year "a- intuited a- ime-hair' a man-year. Deaths c ' urrinc ihr rul.ur:. ;11 < 1 in a Iveh '.ana .ana- *~ have hcen pieced '- a iviii-1 in- -hewn in 1'al.ic n. lu I alia- . .-ii* "A t; ".luce death- 'A have lieu: I -u-pccied" Inn" lli'v r ' -i-e \h :: !i' a *l liie ,;i pcrl.mci* cl llie-e "-tl-pl*l le.l" a-e- in ink ;*, re. a ig llie tv-ult- i 1 llie 'al. ;:ia,;i.c- i- di-i-.ah'e iiefnre fur = lier di-c,! the n.urlalilv rales which are 'lerivui -a ii!' : tahli k-.r i xample. il ii:i|ij'iii- ilial she r.ae inml fur llie proved c.:-c- i.- elii-e **. tp,,- *V\pi eled ran* ha-cd nil tile genet.d p> pula! inn tigure# fur the I'riiviuce. a- vv :!i In* -hnun later, ati'l mi tin- liasis u*i -hi a! ! tin*! eight deaths imm lung cancer amnug the enhert. Actuallv. nine cases vv eiv nh-erieil. it. him ever, the a additional ".-u-|ieeted'" ca.-es were in- cluih*il. incrca-mg 11;is. figure in 12, the t()pi! he very cl< *>l' ! llie >5, lev nf significance. I hic.'ever, h.a\imr fnun.l ju.-t 12 case?, we tire imt almve thi- levi*l and therefore the hyputhi-is tint a-hc-t"- u.iner lu ;/*.' have a higher nicrttilitv fret:: nine cancer than due.- lilt general |i|nl;:ti*:t can net he rejected Wveriiteic--.. the "iiut* teuce nf 12 ia.-e- ill thi.- .-aiti|ile wdilil increase the rate n. a (mint ulucli appmacln tin* significant level, itecau-e n: the trenienilcu.- iii!|icr;;uice el the uicstinnahU. case.- in thi.- iv-nect. -mile detaii regarding them will he given here. In cm* of then* ea-e-. the -ti-jiicinil el .nicer nf llie him; i- ha-cd upon the x*rav interpret,tiinu. and. akhnugh u>, .*uiiu|.-v wa!.erfcr:itei|. the death cerlilicate indicate that death v\a- due * lung i attar. It iwell kiinun that the x ray appearance of hlvfe-'..-. especially if a lectili/.ed deu-itv nr .a superimposed tuliereulnu- lesinn is pres cut. e:m .-imuiate shat nf a lunmr. and liv itself, due.- nut in-lily the inclusion nf this ease a- one nf "proved" cancer cf the lung. A .-eeutid t*;i-e vv a- certified a- having died hy re:i-"li nf hvdrvithtirax. juissilily du tn lum; rale er, hut agatu thetv was nu surgery and im '.n-imnrtem e\;miitt;Uum. In the third ra-i*. ahhuugh it u.i> .-uhjeeled tn auto|i-v. lun |ia!liulugi-t- di-agreevl as u whether lung vaiiwr was j'lv-vnl. The dettth was certitied ;is having been due in ehrrmie inyocarditi.- with nephritis and pulnmnarv euiigesiinn. and pu-sihlv eatieer nf the lung. Uu the basis nf these fact.-, il seem- unwar ranted tn include these three case*= aninug 'I VIII It "ttw'vrvrf" Primary Cancer .if the f.wuj \- `imik-r 1 1 n m Y.s X os Y.* K\|**Siiro vr. in Cut. HI *Cyr. u: Ill V2 yr. m Cal. H Dktl lit 25-frt 7- - yaiy-W Amopsy No Y*i No Asbcsti*5is No Y*s No M2 I'n/. IT, June. 195$ ASARCO ELP 000284*3 LUNG CANCER IN ASBESTOS MINERS "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 both ways. Table 8 gives the rales by age groups. The rates by length of employment are shown in 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 "suspected'' cases are added, one case does show up in this T.UU.F. 8.--Lung Cancer Deaths by Age Groups Table 9.--Lung Cancer Deaths by Length of Employment Number of Persons and Number of Lung Cancer Deaths Length of Employment No. of Deaths No. of ----------------------------------- Persons Proved Total 5-9........................... 10-19............................ 20-29............................ 30-39............................ 40-49............................ 50+............................. 1,795 2.398 922 003 1H5 55 0 t 3 5 0 0 0 1 3 7 l 0 Totals........... 5.958 9 12 Annual Lunjt Cancer Death Kates per 100.000 Man-Years of Kt|>osure Length of Employment Proved Total 5-9. 10-19 20-29 30-39 40-49 flU-r. on M M iaos usao oo Overall....... ....................... 25 34 Number of l'cc?on* and Number of Lunjr Cancer Death? Age tPup No. of No. of ------------------- * D-o--it-h-s------ - I'm sons Proved Total 20-4* ................. 45-54. ..... 55-04..................... M+.......................... Cnl'ti<iu*tt................. 3.901 1.12* 615 315 3 1 l 3 4 0 1 3 3 5 0 Total?.......... 9 12 Annua! l.tme Cumer Death Rates | rr 100.000 M anAeafN of E \l*ourc Age viup Proved Total 20-44.................. 45-54.............. 55-04.. , . 65+____ .. CnknowR............ 44 15 44 51 >1 212 2ta U0 Overall.. . 25 34 j period. This would-produce a rate of 69 per KHj.OOO. again demonstrating the im portance of these nuestionable, but un proved. cases to the final conclusion, because, if there were no cases in this number nt men with long exposure, 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 ami is consistent with the theory of an intrinsic or endogenous factor in can cer. The only other explanation would be that the susceptible members of thi> 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 <>nlv possible error in this interpretation could occur if the weighted exposures were inversely related to years of employment. Tmmk 10.--f.ung Cancer Deaths by Exposure (. atci/ory Number of Person* and Number f Lung Cancer Death- Exposure Category No. of Persons N. of Deaths Proved Total I.......................... II..................... Ilf................... Cnknnwn.. . 2.031 2.150 1.772 5 4 3o 0 4 4 4 0 Totals........ 5.95b 9 12 Annual Lung Cancer Death Rates per 100,000 Man-Years of Exposure Exposure Category Proved Tola ........ ..T............................... II............................... m............................. 1 ukimvvn.. . ... . 33 23 19 0 33 31 37 0 Overall.. . . . . 25 34 Braun--Tntan MS \ ASARCO ELP 0002844. ,i m. .1. .manres nr ixnrsrxi.it. iir.u.ru Table 11.--Xlimber of Persons in / orhnis Weighted Exposure Categories by Length of Employment -___ . ... . -- ... . VcMhM Espusoir* i.ateirorws f^utzthof --........ Employment 1 HI 3-9 iu- 19 to-39 UHy 714* 7u: ,V.ih u*i3 w SM Mi 2i:< 247 21* 37 7. 07 41 24 21 Ml - l*nknown 0 r i 0 Total i.Tvs 2.3ir0sSt I''*! 55 Totals 2.031 Average years if exposure I7.S .',150 17a 11.772 Ifi.li 5 3,955 .-.1.0 in which case the hea\ ie-t weighted ex posure i Categorv Ilf) would -how the shortest length of employment. Table 11. which list.- 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 nonsmoker.-, 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, !>oth "proved" and "-u-pected,'' occurred in smokers. Table 12 was -o striking that it was felt diaf further verification was necessary. Jt was possible that some abnormal distribu tion may have occurred, e. g.. the nou- I'.uilX I.t.--Xumhor nnJ I Vr.. n/.i.,v / >islrihulion .if Smokers ond X.otsm.'kers i>y .-I.;,- Croups ice rou| JtW4.. 5-S4........................ VHW.......................... t'uknown................. . Totala.......... Average age............ Number Viin5intkcr 3/,,nu 411 K.4 2 w.i 221 iU2 n 1.073 :<y.3 1.265 44.2 Unknown 12 4 2 l l 20 40.7 T.\m k 12.- Lung (.*nicer /Veif/i for Xmoksrjt and Numl*er t IVr-oti* liy.*tmSl mNoukitimiJ:n-rHaobfit?I.unc lancer llratli* No. of Deaths lVr*ms t*rv*i| Total Smokers............. Nonsmokers .. . Unknown.. 1.073 ill u u o 12 0 II Totals 5/j.Vt j 12 Annual f.omr Cancer Peith Katr* jer lyu.rtuO Man Year* of Exposure hv Habits Death* l*ri>\el Tot it .1SNm'nwki*ubkntci:wisi.u.k..p....i............................ . .Ti> 0 r< Over-ill............... - 34 ,-mokers nitty have ineludvd tt larger percentage of young men. I'on.-eouenth . ad ditional Tables, 15, 14. ami 15 were con structed to show the distribution of -tnokers and nousmokers by age. length of employ ment. and degree of exposure. Although there tire slight differences, they do not account for the fact that all observed cases of lung cancer were in smokers, fn re.-jiect to age fTable 151 the combined nu-rage age of the smokers was 4.0 years le<- than that of the tion-mokers. Table 14 -hows that as far as length of employment is con- Tahi k 14.--Xundvr imd /Yiviitih/r I h's!rihu!i.m nf Smokvrs oud Xotisnikers I y J.emilii of Employment Lcucth of Employment 6-9 ... 10-19... . 20-29....... . 30-39........................ {HV.................... 504-.............. Totals.... Averaco length of cruployment........ Number rtu'ikrrs YuttsmokefS I.Uk l.'nT 722 133 ; 33 377 420 tU9 HV 76 4.h73 I.203 17.0 10.3 Unknown 10 4 4 0 0 20 10.0 Perrontaire Distribution \fe Group Smoker Xonsnmker 20-44................. . . . 45-64................... . 55-64................... . 054-............................. Unknown............. . . 03.5 iy.2 3.5 * 54.5 17.7 16.0 1124 0.0 Totals... ....... 11)0% H0% Unknown on.O 211.0 10.0 5.0 5.0 100% T^ss than 0.03%. MU Pcrcotitofie Distribution length of Employment 5-9.......................... 10-19....................... 20-29........................ 30- 39...................... 10-49........................ .10+.......................... Totals........ Smoker 30.1 42.1 15.4 9.3 2.4 100% Nonsmoker 20.8 33.7 15.7 13.1 5.9 1.* tno% Unknown 50.0 20.0 10.0 2101..00 0.0 ioo% I'ol. 17, June, 10SS ASARCO ELP 0002845 LUNG CAXCER IS ASBESTOS MIXERS Table 15.--Xumber and Percentage Distribution of Smokers and Xansmokrrs by Exposure Category Ex|K>5ure Category II . m .. C'nkRou'n. Totals.... Average exposure t-ateporj .... Number Smokers Sousmokers I.5.*5y3i 474 452 i.425 333 l 4/73 1.2G5 2.U 1.9 t'nknown 4 9 0 20 2.3 Exposure Category I... 11.... III.. Cnknown Total*, f'1'wnt.iue Distribution Smokftj. :ih.2 Xnusmokers 37 7* 35.7 ,,*S.7 <).! lu% Unknown 20.0 35.0 45.0 0.0 UOCi c-med. lilt- stinkers had worked about 2.3 years its-? <>n the average than the non<nn)ker With lunger exposure and greater age. one would expect the nonsmoking group to show a hitflnr rate if" lung cancer were due to asbestos. 1'altle 15 shows that the average exposure category was almost the -nnu tor me two groups. Therefore, this variable -eeiti'. to he of no importance in accounting tor this difference. The result of this additional analvsis is that none of these factors appears to lessen the effect of Table 12. ('o;/(/ao';.oT ,-.y the (e-,` /f.r/vriV/nv zeith the; ,f tin' Province ./' Oucl'cc. f'i<- inini'V! t amnia. ami the ('nil/ States.-- In oriier to make a comparison of the experienci aiming asbestos miners with that of the gvo.eral population of the Province of Qitehe.. -t.iti'tics were gathered, as stated office of tile I >i\ isinti 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 ami by county for the years 1950 through 1955. In addition, all death certificates which specified primary cancer of the lung, and all those which indicated lung cancer but did not specify the origin, were exam ined for the years 1952 through 1955. Table 16 gives a tabulation of the number of deaths from lung cancer in the Province and in the cohort for the years 1950 through 1955, and shows the annual rate per 109.000 in these segments. It will be noted from the table that the mortality rale for the "proved" cases in the cohort is only slightly higher than the rate for the I'rovince. When the "suspected" cases are included in the calculation, the rate for the cohort rises to 33.8 i>er 1(K),0(X), which is about 50r/c higher than the rate for the Province. This, it will he 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 case' for the Province between 1950 and 1**55. it is assumed that at least part of this increase is due to im proved recognition and reporting of lung cancer during the interval. For this reason, the years 195-1 and 1955 were thought to be more nearly representative of actual condi tions. Kven so. it is quite likely that the general population is not studied for lung cancer with the same diligence with whicl Tuu.r in.-t 'iKparisitn ii ; Cohort with Prttvincc of Outiwr rI'riobv**imri ** Total Pro***! (`Perxocvliundcieng 'worker?* Numberf --- - Ptfrfot> l*..r4 '.'.y'U'od * un :t i ly.'.i 220 j 2ts t.un>: Cancer IVatlw 1942 IM3 1954 245 303 3<*3 03 i* > 245 3*M 1 \ Annual - p*r 1955 Total tnO.OOO 357 1 *24 22.fi 3 \2 39 3.44 l.olj 43.3 25.3 22-4 ! In the Pniv.nc* ficwvt. : Ih^ii n^sunird all male lune cancer death? ar* for men of 20+ { * Approximate nudp;m *f ih** enuiceratr.d population for 1951. and the estimated population for 1931 'P.upporl. Div. de la De mographic- tNumber alive in rh*rt at Wt-inatnc of 1952. Braun -- 7"r;m fH5 ASARCO ELP 0002846 Ape Group 20-44 45-54 55-44 M+ Totals Tmu.e 17.---Lutu; Cancer Deaths for the Province of Quebec9 Kttiniutcd t population 777,000 2u2.f*** 137,ton 121.00U 1.237,000 Number of Deaths 19M Total Certified Specified primary Total Proved Total Proved 17 13 11 9 67 36 43 29 100 36 69 32 lit 33 66 29 295 120 191 99 iv.V Total CYrtifiM Sjtecifiod Primary Total 17 t 117 146 342 Prmed * 35 57 M 1ST. Total 17 55 116 14* 337 Proved 9 32 57 54 152 Abo Group <.V54 ........................... ................. ................... ................... Over-all........................ .................... Death Rates per lOO.UOO 1954 Total Certified Specified Primary Total Proved Total Proved 0 r> 1.7 1.4 1.2 33.2 17.H 21.3 14.4 73.0 *7.7 50.4 23.4 91.7 27.3 56.2 24.0 23.8 9.7 15.4 6.0 1055 Total Certified Total Proved 22 29.7 85.4 122.3 52 17.3 41.6 44.6 S|HiCified Primary Total Proved 2.2 <j?T M.7 122.3 1.2 15.5 41.6 44.6 27.6 12 : 27.2 12.3 4 Data from death certificates. 1 Estimate for population obtained by applying 1951 percentages for age groups for males to the total tHpul;vtiou for 3954. as given in Rapport, Div.de la Demographic. this disease is looked for in the miners, and it seems probable that the mortality rates for 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 bv autopsy, surgery, or biopsy. The term "specified primary" refers to those cases in these two categoric.-, 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 r-preified 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, Miinmarized in Table 18, shows that the observed number of deaths iu 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 t>5 and over, the five deaths provide a figure which is almost significant at the 95' c level. How ever, it should be noted that this number includes one of the suspected hut 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 Aetna/ ami Expected Number of Lung Cancer Deaths by Age Among Asbestos Miners Age Oroup Province Total Specified Primary Rate per 100,000 20-44 45-54 55-64 654Unknown U 24.5 67.6 89.3 ** Observed No. Expected of Deaths No. of No. of . Miner? Deaths Proved Total 3.901 1,124 615 315 3 o2 t 1 1 23 24 -* 0 1 3 3 5 0 The eipccltd number Is based on th averaee otthe 1954 and 1955 aee-sneeinc rates tor the Province ot Quebec, t Actually 0.4. I'ol IT, J.unc. 1958 ASARCO ELP 0002847 LUXC CASCER IS ASBESTOS MISERS Table l1).--Age Distribution of Adult Males for Table 20.--Annual Death Rates per lOOflOO for the Province of Quebec, 1951* Cancer of the Lung in Canada* Age Group 20-44................ 45-54............... 55-64................ *5+................. Total__ i*nv!Into Numl*r PewniHge 727.135 IMS,952 128,944 113,467 63 16 11 10 100 rtrcoiuace in Cohort 5 100 * Support, JSSC i matter of the same intensity of interest as it is in younger jicrsnns. Table 18 also answers a question pre viously raised. It shows that the members t>f the cohort have not died from lung can ter at an age earlier than the general popu lation. ami that -uch an explanation cannot :-e offered for the absence of lung cancer n 240 men with more than 40 years of employment referred to on page 64.1. Before leaving this comparison of the Province with the miners, it should be shown that their age distributions are rea sonably the -amt. That this is the case can >e observed from Table 19. It should be remembered that the miners -cure and consequently, it can be expected bat the oldest age group will be larger in be general population. 1 he data presented n Table 20 'indicate that the lung cancer rate generally decreases a Her age 70. There fore. we could expect the rate for all people vcr Co to be smaller than the rate for the roup la-tween tv and 75. which would apply n the oldest group of miners. It is felt bat bv using the whole adult male populajon. we hate developed rates for the genral population which are somewhat lower ban if we had been able to exclude the jeople in the general population over 75. i A comparison between the aslarstos miners lid the population fit' the Dominion as a hole was made, using statistical material full several sources. In one source. Philps ~3 gave age- and sex-specific rates for anada for three periods between 1931 and ?52. The rates for males are given in able 20. These figures show strikingly the increase i rates between 1931 anti 1952. and this .Kg* ('.roup Cncler 30 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 0-84 85+ AH Ages 1931-11*33 0.2 0.9 2.0 3.0 5.2 3.2 12.7 12.5 15.1 10.7 15.8 8.2 11.4 2.8 Uroups of Years 1941-1943 0.3 0.9 3.2 S.4 12.5 18.9 27.0 33.7 34.5 30.6 30.0 27.9 14.3 7.1 1950-1952 1.0 0.6 3.0 6.5 16.7 37.2 59.7 77.8 102.9 86.3 83.9 59.7 71.0 15.8 "Mortality from Lung Cancer m Canmift." 1031 to 1052. 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: Ace Croup 20-14 45-S4 ;S-C4 65 + Rate 5 27 60 >0.95 These rates are. in general, lower than those developed for the total (proved and suspected i cases of lung cancer among the asbestos miners. The only large difference, however, is in the age group of 65 years and over, and it is quite possible that the rate for this group may have increased for Canada between 1952 and 1954 as it did for the Province of Quebec (Table 17). A further comparison has been made with an over-all rate obtained from the American Cancer Society for respiratory cancer deaths in Canada in 1953. This rate, for males, is 20.8 per 100,000. or 5 more per 100,000 than 'Phillips' 1950-1952 rate, and compares with 25.3 per 100,000 for proved cases and 33.S per 100.000 for total cases among the aun--Truaii 647 ASARCO ELP 0002848 ,' - -v. A. M. A. ARCHll'ES OF INDUSTRIAL HF.AI.TH Table 21.--Number of Deaths and Death Rates per 100,000 by Age Groups for the Adult Male Population of the United States * Age Group JO-M 4$-54 6.V64 Total Population 24.644,000 3.U65.0OU *.*40,000 S.H70.000 44.H19.000 Cases m 2.979 6.254 6.483 16,599 Kate per U 3.6 36.9 98.6 114.3 37.2 Dat* from "Vital Statistics of the United States." Vol. I and 2. 1852. asbestos miners in this study. It is there fore obvious that there are no important differences between the rates for asbestos miners and those for the general 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 tor males, these were 25.3 per KiOXKX) in 1953. and 28.0 per 100,000 in 1955. They are not identical with the rate calculated from the figures of the office of Vital Statistics, but this is possibly because the American Can cer Society rate- are for males of all ages. Nevertheless, they. too. compare favorably with the rate- of 25 for 34 for total cases) obtaining among the asbestos miners. Turning for a moment to a comparison between the asbestos miners and persons who are exposed to asbestos in one form or another ias distinguished from the gen eral population groups just discused. who have no exposure) an interesting observa tion can be developed by deduction. Hueper 58 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 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 ca-e 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 i- 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 rate: were computed on the basis of figures foi the years 1950 through 1955. The eigh counties selected for comparison were Ar gentcuil, Chateaugay. Montmagny. Port neuf. Richlieu. Kiviere-du-Loup. St Hyaeinthe, and Terrebonne, mainly because they represent a wide geographic distribu tion throughout the Pn.>\ ince. The countie selected because of their proximity to til asbestos mines include Arthabaska, Beaucc Drummond. Erontenac. Megantic. Rich mond. Sherhrooke, and Wolfe. Table 2 shows the number of lung cancer death for the years 1950 through 1955 for eac of these counties, and a mortality ratt based on the adult male population in 1953 To emphasize the comparison. Megantij County has been shown separately, as ha( the Province of Quebec and al-o the Pro\ ince with the eight "asbestos-producing counties subtracted. Because of its uniqi lung cancer death rate, Montreal et Isle i Jesus has also been listed in order to provic further comparison. It is apparent from the table that tl lung cancer death rate for the eight count! 648 rot. IT, June, 19 I ASARCO ELP 0002849 LVXG CAXCER IX ASBESTOS MIXERS Tabu: 22.--Xumber r/ Lung Cancer Oeaths and Rate per 100.000 Man-Years Counties Mtfutmic County Eight "Adjacent** Counth*# Eight Selected Counties Province of Quebec Province of Quebec less eleht "adjacent** cuuntles Montreal ft Isle de iesus Adult Mate population lv52 13.100 ilT.lVK) >*3.000 Mt&nuo 1.WQ.MK) 394.000 1930 3 t> 2 196 190 3 1951 1 3 to 220 21" 7 Male Lung Cancer Deaths * 1952 1953 1954 . tV55 33 1 4 ! 1C 4 ir, 3 10 5 9 243 303 303 337 236 287 299 341 156 192 185 225 It is Assumed that till tnnl; lung C"tnrer deaths occurred after age '20. Total 15 54 49 1624 1370 770 Rate tier 100.000 18.9 9.4 9.6 22.6 23.8 32.3 immediately surrounding the ai-bestos-producing areas is practically identical with that of eight counties selected for comparison. While Megontic C"timy has a rate nearly twice that of the combined eight selected counties, it i- lower than the rate for the Trovince. and considerably lower than the rate for Montreal. The figure for Montreal would certainly he 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 alxnir 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 asj bestos-producing areas have any greater I incidence of lung cancer than those who ] live elsewhere in the Province. Comment on All Recorded Rung Cancer Cases, l.iviin/ and Dead, among the Asbes tos Miners.- Although a simple enumera tion of all the known or suspected cases of cancer of the lung in these areas has no particular value from a statistical point of view, it is of interest to summarize such cases for the record. There were nine deaths prior to the beginning of the time period covered by the study, including one in which the. diagnosis was mediastinal lymphosar coma. During the period covered by this investigation, there were nine proved eases and three suspected eases in the cohort. Through 1956 and to date in 1957. there were eight deaths, ,-ix of which were merelv 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. Tn addition, there are now living four cases in which the diagnostic evidence is strongly suggestive of lung cancer. This is a total of 33 cases of all types, including 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 inert 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 HI. and six worked in an exposure represented by Category I. There were only 17 among these proved lung cancer cases in which we have in formation regarding the presence of asbestosis. 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 (WO ASARCO ELP 0002850 [Wi A. M. A. ARCHIVES OF IS'ULSTRtAL 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 exposure and who were in the industry in 1950. Data relative to their characteristics were collected and their status at the end of a six-year period of observation was de termined. In the case of those who had 'died, an exhaustive search of death certif icates and insurance records was carried out in order to determine ns 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. ItI 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,-1 000. When the three "suspected'' cases werej added, the "total" rate for the cohort rose; to 33.8. The importance of the suspected! ' but unproved cases in determining these I rates has been reiterated because it is likely; that such cases would not be included ini the statistics for the general population andi because thev influence the results so mark-- edty. * ! 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 which presents strong evidence against the carcinogenicity of asbestos. Comparison of the. experience among the asbestos miners with that of various seg ments of the unexposed. comparable popu lation shows that the observed number ofdeaths among the miners is not significantly greater than the expected number. The rate for proved cases among the asbestos miners f25.3 per 100,0001 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 I \il. IT, June, JOSS ASARCO ELP 0002851 LCXG CANCER IX ASBESTOS MIXERS I of 37.2, 25.3, and 28.0 obtained from various 6. Behrens, W.: Exiierimental Asbestosis, sources for adult males in the United States. Finally, in this matter of comparison, it would appear that the world-wide experience of persons exposed to asbestos dust is not Schweiz. Ztschr. allg. Path. 14:275-297, 1951. 7. Behrens, W., Jr.: The Clinical Picture and Pathology of Asbestosis, Ztschr. Unfallmed. u. Berufskrankh. 45:129-140 (June 15) 1952. 8. Berblinger, W.: Increase of Lung Cancer worse with respect to lung cancer than that and Diseases Due to Dust Inhalation. Med. Klin. of the unexposed population. The counties surrounding the asbestos- producing areas, in which it is presumed most of the asbestos miners live, have al 27-.1357-1342 (Sept. 11) 1931. 9. Bcrenblum, I.: Irritation and Carcinogenesis, Arch. Path. 38:233-244 (Oct.) 1944. 10. Botinc: Asbestosis, Deutsche med. VVciinschr. 62:928-930 (June 5) 1936. most identical mortality rates with those of 11. Bohme, A.: Results of Periodical Examina eight counties widely scattered through the tions of Workers in an Asbestos Factory, Beitr. Province, and are lower than those for the Silikose Forsrh. 11:34. 1951. remainder of the Province, and much lower than the rate for Montreal. Since 1940 there have been 1V cases in which the <liugiiu*is of primary cancer of the iting may he emi-idered to have been proved. Vppripximaieit half of these cases were ,i.---dated uiih .i.-lie.-ln-i.-. .Ml hot one 12 Bowles, ().: Ashc-stos-Milliug. Marketing ainl Fabrii-ation. Information Circular Xo. 6869, l' S. Department of the Interior. Bureau of Mine-. 1955, [,p. ] -A,. 15. Breslovv. I..; Ih.ingliu, I..; Kustmti-eu. G.. and Abrams. H. K.: (-)ccup.itiwns and Cigarette Smoking a- Factnvs in I.nng Cancer. Am. 1. Pul-. Health. 44:171-181 1Feb.) 1954. died in tiie recognized "eaneer-age" and at lea-! one-third had only the lightest t-xpo-itre > t ategory i i to a-he-los dtl-t. tin the ha--- of vtliat are believed to he complete and r- liable data, it -cents tair to conclude that the `she-to- miners in the Province of (Juehec do not have a signif 14. Bn*tnl, L. J.: Roentgenologic As|>crts of Siliru-i*. and Ashe-tosis, A. M. A. Arch. Indust. Health 11:189.195 1 March) 1955. 15. Cancer of the Lung: An Evaluation of the Problem. Proceedings of the Scientific Section, Annual Meeting. American Cancer Society, Inc., Xnv 3-4, 195J, New York. American Cancer Society. Inc.. 1956. icantly higher death rate from lung cancer titan do coinpatahle segments of the general poptii.itioii I'ttrtiiv v:i o'-<. the d.-ath rate from lung -.iiuvr til rite .i'v.is contiguous to the a.-he-- to- iiper.i-ioii- i- comparable to that, in areas widely -ralti-rcd throughout the Prov ince of 16. ('artier. P : Asbestosis Cancer of die Lung, in discussion on Smith. W. E.: Survey ot Some Current llriti-h and F.um|iean Studies of Occupa tional Tumor. Problems. A M. A. Arch. Indust. live 5 -2ti2-26J, 1952. 17 Cartier, P.: Suite Clinical Observations of A.-besto-is in Mine and Mill Workers. A. M. A. Arch. Indust. Health 11:34-207 1 March) 1955. tjuehec .:*id - lower than in -mie urban ized an i- uttliie tin- Primme. 18. Clcrcns, J Research into Pulmonary Aabeslo-is in Belgium, Arch, la-lges med. Soviale 8:557505 1 Xnv.) 1951. REFERENCES * 1 At:.-.;. I.-eoii.ii". R Bronchial Carcinoma: Review ' Jisi v a*v--. j lim-riim Cull. Surgeons ` 2o:.tr5-.'r,i i Sep* j 1 150 . J. Alien. M. !. Brotu-biogcnic Carcinoma As- -""iaieil u::i 1 `mn..,-nt;io-:-: Repon of 2 - t .t-e-. J li-'-i-" Mv-j Ui-.Mii-.v4/ i Xnv. i pi.ij, 3. turinr. 1`. \ "mriliutinn to the Study of A-l-c*i. -i.. \-.v.-.H n::i! pnvfc-*. 1M ASff-511, l'4'*l 4. Aiiili-r-...-i. V S. si.il Dil-le. J. H : Silioo-is and Carciuon <; :l-e l.nne. 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Hvg. 4:221-235 (Sept.) 1951. Braun--Truan 653 i ASARCO ELP 0002854