Document 44NxqVGLYE41Bo7VpjdRLYddV

''V -1 m sxtltj P-i, mil ^r;i g i **-<. jy *M{ \ Mi Wi M -Jil. ffi m rf^M I '. i ' ' M"'. IM - 4`. An Epidemiological Study of Lung Cancer in Asbestos Miners C>1^rw LJt .,tVv y y. y (^0 c.' J XW liM I w? .j.r.Yb C . I.Y( 7./V ; |is no reliable cr;. Ijsiticipatc enreiti'' |known, relative!}' $ structure of a che: L-ieiit to <liiuiiii-.li J action. DANIIL C. BRAUN, M.D.. and T. DAVID TRUAN, M.A., Pittsburgh UP If asbestos is ir. Icarcinogen, the tu 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 dements in the environment of man. The approach used by some workers lias been to suspect one or several sub stances and then set aimut in an intensive search for lung cancer among jtersons who | some property w whose work is also frequently referred te | something more th as establishing a connection between asl>.-> tosis and cancer of the lung, reported in 1951 that cancer of the lung was present These authors j until some more |direct carcinogens- in 14.1 c/c of asbestosis cases examined by him. In 1941, Nordtnann and Sorgo*' claimed to Live produced lung cancer in mice which they exposed to asbestos dim. ^composition prudu J asbestos niight !*_Icinogen" which on ,-elopment of a have had any exposure to t!u#>e materials. Since 1951. additional cases of cancer of t brought about by- In this connection, Smith 82 writes: "The the lung. coexisting with asliestosis h,in- ;;hc asbestos, such tendency of authors reporting; the coinci been reported, and, according to Hueper5' . Thus the literate; dental occurrence of primary lung cancer about 100 such cases had been reported up jport the thesis th: with silicosis or with any other theoretical to 1955. As a result, an association between Iviray related to th dialogic conditions, has been to emphasize the two diseases appears to have been ac * cancer, is by no i the percentage relationship in extremely cepted by many authors.jand several writers Igether, it is perha small series of cases, with control cases were using the term "asbestosis cancer" of * enlightening. A cr which are not in any way comparable." the lung. \Ycrber,M) in 1952, stated cate j the majority of th Tt 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 gorically that in 7c/r to 17cr of cases of asbestosis. after a latent period of about ]/. to 20 years, carcinoma Incomes estab lished in the lung. On the other hand, not till authors ac cepted this alleged association without , not tpidemiologica t inc. uts neee.ssar'v epidemiological tec ! and most of the au ;o having done so | that succeeding am autopsy and provide a ready source of reservation. Saiqie so in 1939 reported that jsioiis and-genera!!. material for study. Tt was in this way that he had discovered no cases of lung cancer 1 the works which th reports of the simultaneous occurrence of among (>20 cases of asbestosis which he (example, have we lung cancer and asbestosis began to accu had examined; and in 1942, Holleb and population of as!> mulate after the report of a case by Lynch Angrist 48 expressed the opinion that the several authors w! and Smith 68 in 1935. Within the next 10 number of cases of asbestosis with lung served incidence of years, about 15 additional cases were re ported, and in 1954 Merewether76 reviewed all deaths from asbestosis recorded in Eng land since March. 1924. Lung cancer oc curred in 16r,c of these cases. Gloyne.41 Accepted for publication Jan. 29, 1058. This study was made possible thrnuyli a grant from the Quebec Asliestos Mining Association. cancer was too small for statistical evalua of persons toko al tion. In 1947, Wegelius88 reported 126 ! that this incidence : radiological!}* diagnosed cases of asbestosis ers, generally. V. among 476 workers in Finland, and found unable to find an no cases of lung cancer in this group. I calculated the inc Goldblatt and Goldblatt in their section of among a populatio Merewether's latest book,11 state: "But at asbestosis, and not no stage in all these impressive researches , autopsy. With the Medical Director (Dr. lirnim) assd Statistical Consultant (Mr. Trunu), industrial Hygiene Foundation. 6.14 iwas any clue obtained which might have ' i by Loll,28 i. ne of offered any support to the possibility that ; data on e, k-sure asbestos could act as a carcinogen. There j and even"!lull's ; 1 firmni--Truan r?s8 'TSr-.- , , no reliable criterion by which imc can : oticipate carcinogenicity and, as is well J nown, relatively minute changes in the nurture of a chemical carcinogen are su(ti nt to diminish or eliminate carcinogenic ction. If asbestos is indeed to he regarded as a yjarcitiogcn, the need is felt to deinoiislrate ue property which can i>c regarded as ferred to -Something more than inertness." en asbes- These authors advance the theory that, >orted in ktil some more experimental evidence ot 5 present direct carcinogenesis by asbestos or a de nined bv composition product of it can he obtained. Sorge 'Ssbestos might he considered as a "cw-car- aneer in fjinogen" which only induces a further de 'tos dti.s:. velopment of a preneoplastic condition ancer of |rought about by something independent of fsis have e asbestos, such as .an endogenous factor. fueper Thus the literature, while tending t sup- ortcd up |ort the thesis that asbestosis is in some ' between .jay related to the development of lung been ac- icer, is by no means unanimous. Alto- d writers her, it is perhaps more confusing than cer" of ^lightening. A careful review shows that fed cate- *he majority of the reports are clinical and cases of lot epidemiological. They lack many ele f about ments necessary for the application of es estab- idemiological techniques to their content, ,d most of the authors do not make claim j thors ac- 4 having done so. What has happened is without That succeeding authors have drawn conclu sions and generalized beyond the scope of rted that SS cancer vhich 1^ she works which they quote. Nowhere, for jxample, have we found references to a population of asbestos workers, although <Ueb and that the Jeveral authors who have quoted the ob ith lung served incidence of lung cancer in autopsies evalua if persons who also hail ashestosis imply Ihat this incidence applies to asbestos work ted 12fi ers, generally. We have likewise been sbestosis *d foumj inable to find any study which actually i group, Calculated the incidence of lung cancer ijnong a population of persons who had action of Isbestosis, and not just those who came to "But at iutopsv. With the exception of a 5viper -searches '"jy Doll,28 none of those reviewed gave any ?ht have lata on exposure and dust concentrations. *hty th.it Wl even Doll's paper merely mentions * There .1V. raurt--Truan "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 "ashestosis." as used, may refer to changes observable only by microscopic examination of the lung tissue, or it may mean a radio logical!v detectable condition. Most of the published reports obviously included women among their cases, but some of them do not give the number or proportion of women involved in the study. There is also a lack of uniformity as to what type of exposure most studies have dealt with. Of 99 cases enumerated by I lueper in 1955, only 10 appear to have originated in the United States, and 7 in Canada. Some of the earlier reports ap parently included asbestos miners, but it can be assumed, since 82 of the 99 cases had originated in England, and- since no asbestos mining operations are carried on in that country, that most of the reported cases have involved workers in the textile or fabricating industries. Such factors as smoking habits, family history^ of cancer, length of time in the industry, and age of the individual case arealso 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. One of the most detailed studies and one which deserves the most serious considera tion is that reported by Doll23 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. 635 i- ' !' ^. #fr'VK. ` > '5 , ' - t -,, Is,' l,t .V . .4' r\r. ' '' i ii :4 &- k- * & Sr I *'r 4 st 'i % it. .1/. I><tl concluded that hint; cancer was a J'Jk-- I. AKCltm s or IXHI STKI. H- UliAI.TH /.('.VC C.l 11 UuiJ* QUt ri* ill oilier torn is of | 'neuinoconio- death cert citie industrial hazard of certain asbestos Ms vva.s , and in 106 eases which have beer. workers and that, after 20 years of expo proved not to have atn type <f I'tieumo- ,5 enhance sure, the risk is 10 limes as great as for coniosis it w;t s 8.3(7, Gloyne considered -hat the ir the general j>opiilatioti. "llu` mot lalitv of the as icstos workers" to dcs of the This article is important for several rea sons, in addition to the definite conclusions at which it arrives. I`or example, it liegitts be "disturbing " First i f all. it is obvious that the :q.er does not < 'cal w th the "mortalily of asbestos workc rs," ; nd secondlv. The dang rate toum the gener: by stating that "in view of the infrequency it must be borne in mind that all of Dr. l,ige. occup of asbestosis, this large number of cases (iloyne's cases were submitted to him for j.ueh as sr. (61 cases of lung cancer') suggests--but study because the findings were unusi'al I Lvitch."" does not prove- -that lung cancer is an for uncomplicated pneumoconiosis. * It can i^e first c: occupational hazard of asbestos workers." reasonably be assumed that cases, including !oarcinoma Neither this article nor any previous one those of asbestosis. in which the finding, jjutopsies < which we have examined presents any fig were not considered unusual were not sent (faeturing j ures to prove that tisbcstosis is an infre to Dr. Gloyne for examination. As a mat |*deinonstra quent occurrence. Kstimatcs of the number ter of fact, in the same paragraph in which 'tings." T; of persons i>tenlially exposed to asbestos he expresses concern over the incidence identical w dust in the I'nilcd States alone vary from rate in asbestosis. Dr. Gloyne himself Ihimself. p<- 10,000 to 35,000, and the incidence of as points out that the rate for lung cancer incidence < bestosis of any degree might t>e. higher than based on necropsies at the London Chest Lniall for Doll imagines. This study, like so many others, involves autopsy records. The number of jktsous 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 (lung cancer) may he a hazard (in asbestos workers) has lx-en 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 tin's group, an incidence rate of 14.1(4 for lung cancer among asbestosis cases coming to autopsy. Hospital was 21.3(4 while the figures of jdculation.' the Kegistnir-Gener.il showed only 2.4(4 -have used ; He thus recognized that autopsies on a cer- I ;or an ass*- tain selected group of cases were not rep- '.A-jth ashes: resentative of the general population, h glotz u3 tV would seem. then, that notwithstanding the ases of In value of Dr. Gloyne's work, its importance dimes as !; as an index of the prevalence of lung can- Ijsbeslosis. cer in asliestolics lias been misinterpreted i Behrens by some who have quoted him. All that it l^gted that really shows is the fact that in a group of tjiterature. - 121 cases, selected for special study prj_ 5' the- lung--c marily because they seemed abnormal bv 'This is an preliminary examination. 17. or 14.1(4, had incidence < lung cancer. tchich were Merewether 75 in 1947, in the report of cause some the Chief Inspector of Factories, reviewed |possibly hi all cases reported between 1924 and 1946 leases were in which asbestosis was the cause of death i plies to the or a coexisting condition. This work was Appears to later extended to include till such cases re iiutopsies ported up to December, 1654, by which time j.vhicli 6 cast there were 344 deaths, including 205 males formation t: and 139 females. Among them were 55 not justify cases (16(7) of cancer of the lung, 41 in mortality rat There were in his scries 796 cases with sili males and 14 in females. It is quite possible Perhaps i cosis, and 6.9(y of these also showed pri that a large number of asbestotics who did <ivelv oil tl mary cancer of the hiug. The incidence of not die of their aslwstosis, or in whose [n 1955 he 636 fill. 17, June, /9-v Jraiot- -Tman AgeZ** s ** ' ' 7X***-( TRIAL HEALTH %-V(7 CAXCIiR IX ASHIiSTOS MIXERS --of pncumoconio- sjeatli certificate it was not mentioned, may 169 cases which save been missed. The import of this 16% type of pneumo- |s enhanced by the simultaneous statement loyne considered iiiat the incidence of lung cancer in autopstos workers" tr- *><"$ of the general population is only 1%. all, it is obvious jfhe danger of attempting to com{>are a d with the "mor- *ite found in 344 cases with the rate for and secondly, the general population without res(x_*ct to that all of. Dr. Ige, occupation, and many other variables, itted to him for itch as smoking habits, is obvious, s were unusual | Lynch,70 who with Smith es had reported coniosis. It can -he first case in 1935, reported 4 cases of . cases, including ^rcinoina of the lung in a series of 49 itch the findings Autopsies on workers in an asbestos manu al were not sent yacturing plant who were shown to have .tion. As a mat tdemonstrable deposits of asbestos in the agraph in which Lngs." This, of course, is not necessarily r the incidence ,-jentical with the disease asbestosis. Lynch, Gloyne himself linself, points out that, although this is an for lung cancer Lcidence of 8.2%, "laoth figures are too ` London Chest !,rnall for very serious statistical types of * the figures of |dculation." Nevertheless, later writers ved only ,2.4%. ^ve used this paper to strengthen the case topstes on a cer- 4or an association of carcinoma of the lung s were not rep- yith asbestosis. It is also of interest that population. Tr *;iotz83 found only the same number of withstanding the loses of lung cancer in a series nearly 10 its.importance vines as large, i. e., 4 in 478 cases of tee of lung can- |>bestosis. l misinterpreted jgehrens, as cited by Merewether,78 estihim. All that it \ated that, of 309 cases of asbestosis in the t in a group of Aernture, 44 showed associated cancer of ecial study pri- |,e lung--giving an incidence of 14.2%. 4 abnormal by |hjs js an illustration of generalizing an j , or 14.1%, had lcidence obtained in a group of cases j |hich were undoubtedly reported only beI n the report of iiuse some of them showed lung cancer, to I tories, reviewed possibly hundreds of asbestotics whose j 1924 and 1946 hses were never reported. The same ap I cause of death -'dies to the conclusion of Telekv,83 who This work was spears to have reviewed reports of 39 ! such cases re- '.jtopsies on persons with asbestosis among I l, by which time |hich 6 cases of lung cancer occurred. In i .ding 205 males jormation from sources such as these does them were 55 lot justify generalizations with regard to j the lung, 41 in |ortality rates. | is quite possible j Perhaps no one has written so extenstotics who did Jvely on the subject as has llueper.5-59 jn, or in whose 1955 he reviewed the cases** reported I of. IT, June, i95,y Ljwn--Truan prior to that dale and enumerated a total of 99. Pleven of these were those dis cussed by Doll28 and may have been cases covered by other authors. Light were dis covered by Kemiaway and Kennaway in an analysis of death certificates, and, unless Merewothcr'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 Merewether and the 17 by Gloyne contain some duplica tion with each other or with those of other English authors. Principles of the Epidemiological Method Dorn 30 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 terial, particularly surgical and autopsy records, supplemented to 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 by the same methods that have proved so successful previously in the study of communicable diseases, that is to say, by epidemiological methods. 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 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 be^n available to the author. In order to draw a generalization regarding all asl>est(>s ' workers, it is necessary for a study to in clude living persons as well as the dead. 637 t-i". i r. V * :!< $ '1:1 !J{ 4-a .f'-/Mitia'i M i f>ts'f J*i ** *r . a. m. a. arciurns or industriai. iii-.ai.tii : ;.r\t; CA.xcr.it . Limiting the investig.itinn 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, ns 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 [M>pulation 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 fl) 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: (3) comparing the relative frequency 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 Duly sites, may result in finding a higher jiercentage (relative frequency) 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.3" 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 iti dealing with such samples, the observer may easily find more eases of a given disease than would fi.?K lie found in another group of the same size, ' discussions with but representative of the general population. of the asbestos It is true that investigation of cases from with clinicians, p, such a sample can furnish information i of City and Fro valuable for research, but the use of this .iiul ol the t an., information in drawing generalizations is other interested [ necessarily restricted. It is the obligation niorbidity data, a: of both the investigator and of those who were available fr read his report to make proper comparisons hospitals in Mon: and to draw only those conclusions which the 13 cancer detc are valid and justified. A good statistical ince. However. ! study of cases of cancer of the lung occur . taiity in lung ca: ring in a group of autopsies can lead to a to depend upon proper inference concerning the frequence These we found of lung cancer among cases coming to vital statistics de| autopsy, but only to such cases. For in of I lealthJn,,Quci formation from such a study to be pro liminary survey, it jected to some larger group, it is necessary Dive and detailo that the autopsies represent a good sample fathered with reT of that larger group. To assume that such employed in the is; the case in any particular series is dan . irtd the mortality gerous and likely to be false. population. There is some danger that the figures Following this reported by some authors may be miscon initial effort was < strued as applying to asbestos workers or of data relating ! even asbestos miners, when, in fact, tbe been processed th: authors in question do not make this gen ford Mines since i eralization. nor can the generalization be dmilar informath made for the reasons stated. L lose study of :it Asbestos, Quc. the reports reveals that the percentages records included t* cited relate only to the group of autopsies sonal medical his covered by the particular investigation. number of years t The present study, in contrast to the of weighted expo- earlier works, has been planned to utilize the individual's he the epidemiological method. A well-defined j)t his death. group of asbestos miners has been estab From this inter lished in such a way that it constitutes a to formulate a "coh good sample of the whole population of defined, should be asbestos miners in Quebec. Data for all whole group, and c members of this group have been collected definite period of ti; and analyzed. Those concerning lung can experience indicate- cer have received most careful considera tion. Details of the methods employed will he set forth later, but tbe type of approach is considered to permit of fair comparisons and valid generalizations. of asbestosis in less posine must lie so iuglv, the cohort w: every miner who h. five or more years, Collection and Analysis of Data employment rolls in ` A preliminary survey of potential sources' sionexposed persona of information in February, 1956, involved of employment, we l ol IT. /line. 1t/t.f mint--Triton health U`.Y<; CASTER IK ASBESTOS MIXERS line size, |iscussions with the physicians in charge pulation. -jf the asbestos. companies' programs and >es from Vith clinicians, pathologists, re[>resentatives ormation y City and Provincial health departments of this jid of the Canadian Cancer Society, and itions is her interested persons, it was found that bligation ose who turbidity data, although somewhat limited, j-ere available from such sources as the parisons -uspitals in Montreal and Quebec City, and iie 13 cancer detection centers in the Prov- s which Ve. However, because of the high mor tatistical g occur- ality in lung cancer, it seemed advisable d to a equency ning to \j> depend upon data relating to deaths, ifhese we found to be obtainable at the jital statistics department of the Ministry For in- .if Health in Quebec City. From the pre liminary survey, it was apparent that exten be prc>- sive and detailed information could be icessary ithered with respect to both the persons sample tnployed in the asl>estos mining industry at is such dan- jiid the mortality Population. figures for the general Following this exploratory survey, the aitial effort was directed to the collection If data relating to all workers who had ieen processed through the clinic at Thet*ord Mines since its inception in 1947, and jintilnr information regarding ..11 workers Asbestos, Que. Data from the clinical Vords included the age, family and per sonal medical histories, smoking habits, .lumber of years of exposure, an estimate If weighted exposure, and the course of individual's health status or the cause ,f his death. , From this information it was possible formulate a "cohort" which could be well 'Refined, should be representative of the iliole group, and could be followed for a lefinite period of time. All of the available Experience indicates that the development |f asbestosis in less than five years of ex posure must be somewhat rare. Accord ingly, the cohort was defined as including kery miner who had a total exposure of |ve or more years, and who was on the Employment rolls in 1950. Office and other ionexposed personnel, regardless of length >urccs jf employment, were not included. This solved JniH/i--Truan ' Ms 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 (he living and the known dead had been tabulated. The\' represent men who had left employ ment through retirement or resignation. F.veutually, 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 not an autopsy was performed. Cases in which lung cancer was given as a cause of death, but in which it was not specified as to whether the cancer originated in the lung, were also reviewed in an effort to include all instances of primary carcinoma of the lung in the study. The statistics for the Province of Quebec relate to population, total deaths from all causes, total deaths from cancer of all types, and deaths'from lung cancer. These were collected and tabulated by counties and by sex for the years 1950 to 1955, inclusive. . 63> . :<. r;<YW8S'V u> S'!i i b M.%;! i a55; i(' u SI i, *4 as or.f. if. a. Anani ixdustriai. hhalth ilung cas From them, dentil rates for the general population of Quebec ami of individual counties were calculated for specific years and analyzed by cause. Practically nil employees of om* 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 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 but still living, has been tabulated and analyzed. They will l>e discussed separ ately from those included in the population and time-interval under study. ftABI-K 1.--.Y Age JM4-- ! ii-54... few are not covered by this policy, and A comparison of lung cancer mortality Less than 0.1' 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 in the asbestos-producing counties has been made with that in counties which are far areas. For . removed from the asbestos mines aiul in ! assumption : which, presumably, no asbestos miners live. | ship betwee: IFinally, in order to broaden the compari son of death rates ill different population groups, the rates have been collected for that Catego: Category II. goryj. _ all death claims paid under the policy, and Canada generally, and for the United States, particular notice was taken of the claims according to the most recent published and t in which the proof of death was based on unpublished material. . j Taiii.k 3.--A' \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 bv 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 cancer of the lung is con sidered to have been proved as the cause of death. A few eases in which lung cancer is strongly suspected hut not proved as the cause of death were considered separately. Mortality rates have l>cen calculated using both the "proved" and the total of '`proved" Results and Interpretation The cuhort 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; OriuiiMi r.ilu.ti !,!*.( l>clnn*l Kinal CuUurt Living iu 1955 (working ami retired) iVttrf by 1955 Cancer of lung OurMion;ilIt* cancer of lung . C tther causes Unknown causes Smoker-. N'oii'itiolirfs I'ltktiouit rtt0Ql jjj S,95| $#77| jj7 9 j ^ 4,{7j *i,26 2a Exposure Cswcfcory I................ II..................... UInllk.n..o..w...n...................... Trials.. Aver.i^nxpsure !.oss than 0..'' The four;' similarly tab 4. This was tion was avai regarded as besides the c influence the As used in smoker refer and "suspected" eases during the vears un Tables 1. 2, 3, and 4 present age, number der observation. Comparisons were then of years of employment, weighted average T made between the death rates from the same exposure, and smoking habits of the cohort. cause among specific segments of unexposed A comparison of the exposure to asbestos persons. All lung cancer deaths. lx>th dust is presented in Table 3. All members suspected and prove*!, were carefullv ana of the cohort were placed in one of three V.-ur lyzed to determine possible relationship or correlations between the development of lung cancer and any factor known from the categories, representing increasing degrees of exjwsure based on a weighted average of the years spent at various levels of 1950. 1951. 1952. 1953. HIM. clinical records, such as family history of dustiness. The degree of dustiness for each Totals.... cancer, personal history of heavy smoking, job category was determined after consulta *`J*rov*r* mfc p*r ' coexistence of ashestosis. or exposure to tion with persons familiar with the environ asbestos. ' ment and conditions in the various work Total" rate i**r l ' 640 / '"I. IT. June. Braun--Truan IAL HEALTH h,UNG CANCER IN ASBESTOS MINERS of deaths oc ring the years vn death from as every case been tabulated scussed separthe population |fA*t-K 1.--Number Ace S-M........ 4-54.......... \VM.......... . ,4+....... . Unknown., Totals., kverage Age..., and Percentage Distribution by Age Number 31,,9316012115345 5,9- 64H-1 Per Cent 1--601150690 . icer mortality ' Less than 0.5%. nties has been vhich are far ireas. For the puqxises of calculation, the mines and in jissuniption has been made that the relation s miners live. ship between these categories is linear, and 1 the compari- Jthat Category II is twice as dusty, and nt population Category 'W i. III three times as dusty as Cate- collected for United States, pqblished anu Table 3.--Number and. Percentage Distribution by Exposure Category Table 2.--Number and Percentage Distribution by Length of Employment Employment Number 3245105000U---43210+9990........................................................................................................................................................................... ............ AverageTyoetaarlss.o.t.e..m..p.lo..y.m..e.n.t............. 251...,*3996.7195052.H01H5352.558 Per Cent 134--011:0006i0* ually smoking more than live cigarettes per day. Persons who stnoke 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 4.--Number and_ Percentage Distribution by Smoking Habits ;Ixpoeure -tation Category -n I......... . ructed accord- II .......... III ......... the preceding |Unknown.. dividually and Totals......... \venge Exposure.. 1 population, i-----------------be presented I * ^than 01%- Number 2,031 2,190 1,772 9 --5.958 2.0 Per Cent 34 36 30 -- 100 Smoking Habits Smokers......... ............................ Nonsmokers......... .................... ........... Unknown................................. ........... Totals.......................... ........... Number 1,265 20 -- ... _J,958 I.ess than 0.5%. Ter Cent 79 21 -- 100 < of the study: The fourth variable, smoking habits, was <i09i ^similarly tabulated and is shown in Table 5 914. This was included because the informa- s.?7i dtion was available and because smoking was Jregnnled as one of the variables which, j|besides the environment, cpuld conceivably **6 ^influence the development of lung cancer. ;As used in this presentation, the term 1,265 20 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 supjiorted by an autopsy or surgical resection of the lung with microscopic examination of the re moved tissue, la one case so considered, however, diagnosis was continued by bron- t age, number jhted average | of the cohort, Table 5.--Ycar-by-Ycar Experience of Cohort and Death Rates per 100,000 Man-Years of Risk re to asbestos All members j one of three! Year No. AUve At Beginning o| Year ising degrees 1950............................ ... ! 1961............................ ... fhted average .] 1952............................ 1953............................ .... us levels of3 1954............................ ... 1955............................ 5.958 5,942 5,922 5.848 Proved Primary Ca. of Lung l 2 0 2 l 3 Cause of Death Suspected Primary Ca. of Lun? Ollier Causes 2 12 0 17 0 37 34 0 33 0 36 Unknown l 1 0 0 4 0 ness for each Totals......... ft9 31 169 fter consulta- -i'rovml" mlo |**r 100,000 nmn-yearsof risk* 35.271.5 1 the environ-. _12__ various work *Total" rule per ICO,000 man-years of risk* 35,271.5 ` Man-Years of Risk 5,950 5,932 5,903.5 5,866.5 5,829 5,790.5 35,271.5 17. June, ]<s!>h Braun--Truan 641 `1 srr A. M. A. ARCHIVES OE IXPUSTRIAL UE.AI.TII 1 I.CSC CASTER IX Case No. 1 2 3 4 5 6 -? H 9 A( GO 65 05 59 4H 61 56 37 66 Tabu; 6.--"Proved" Cases of Primary Cancer of the Lung Smoker Yes Yes Yes YoS Yes Yes Yes Yes Yes Exposure 26 yr. In Cat. 11 34 yr. in Oat. 1 37 yr. In Cat. 1 32 yr. In Cut. I 2*2 yr. In Cat. U 33 yr. In Cat. Ill 30 yr. in Cat. II 10 yr. in Cat. 1 2H yr. In Cal. Ill Died 10-12-51 5- 3-55 7-31-55 K-'Jl) 5t| -51 4-30-53 11-22 53 X- 5-M 5- -5ft Autopay Yes Yes No Yes Yes Yes Yea Yes UnHH'li. ' Ashestoais Yes No No No Yes Yes Yes No No choscopy 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 numlier of men at risk for the year under observation. A person who lived throughout the year was counted as a full man-year of risk, but one who died during the year was counted as one-half a man-year. Deaths occurring in the cohort, and in which lung cancer is considered to have been proved as a cause, are shown in Table 6. In Table 7 are shown three deaths which have been considered as '`suspected" lung cancer cases. ' An indication of the importance of these "suspected" cases in interpreting the results of the calculations is desirable before fur ther discussion of the mortality rates which arc derived in later tables, bur example, it hapi>ens 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 95level 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 |u,,g 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 {mint which approaches the significant level. Ilecause 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-rav 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 iulx.-rcvrl<>us 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. A second case was certified as having died by reason of hvdrothorax, possibly dm., to lung cancer, but again there was no surgery and no postmortem examination. In the third case, although it was subjected to autopsy, two pathologists disagreed as to whether lung cancer was present. The death was certified as having been due to chronic myocarditis with nephritis and pulmonary congestion, and possiMy cancer of the lung On the basis of these facts, it seems unwar ranted to include these three cases among Tabi.e 7.--'`Suspected" Primary Cancer of the Lung Case No. 1 2 3 AW 49 4f 65 Smoker Yes Yes Yes Ksposure 1 32 yr. In Oat. Ill ' 33 vr. In Out. III . 42 yr. In Cut. II Died 10-25-50 7- -53 9- 30 55 Autopsy No Yes No . Asbcstosls No Yes No "proved" instances other hand, they car. : regarded completely. \ that mortality rate? both ways. Table S gives the r The rates by loin shown m Table 9. L of employment, the tion which seems p ' were growing older years of ex[>osure : ; cases reported for a ing the six years, or of ex|H)Stire. When are added, une.case Tabi.e 8.--Luna C ' Gr Nnmher of Persons a::.'! Ni Ago Group 20-14.............................. 45-54.............................. 55-4.................................. 65+................................ Unknown..................... Totals............. No.. Verso 3.90 U2 SI 31 5.v5 Annual T-uni:MaCns-eYreearr- Ago group JO-44......... 45-54......... 55-64........ . 65+ ......... Unknown. Over-all.......................... | period. This would per 100,000, again i portance of these proved, cases to : because, if there w number of men with asbestos is a carcinog concluded that these strated considerable r< logical phenomenon w previously and is con. of an intrinsic or end cer. The only other that the susceptible 'group had died earlier 18, which appears Iat Cot. IT, June, 795,? Praun--Truan ! HALT!I CAXCl:-R /.V ASBESTOS MIXHRS Yproved" instances of lung cancer, On the -= .iyther hand, they cannot, in fairness, be dis lOStOSU regarded completely. It is for this reason Vos No ^hat mortality rates have been calculated No No both ways. Vi'oos* Table 8 gives the rates by age groups. Ves 4o The rates by length of employment are Jo &hown tn Table 9. During the first 40 years V employment, the rate rises, an observa- ?'e jtion which seems plausible since the men ^US* *ere ?row`n? older. However, after 40 - and Years of exposure there are no "proved" miners jases reported for a total of 240 men dur- Ur> ing the six years, or aliout 1440 man-years *n can- 3 f exjtosure. When the "susj)ected" cases CCUr* `4re added, one case does show up in this would :i oaches e tre- Table 8.--Lung Cancer Deaths by Age Groups onable Number of Persons and Number of Lung Cancer Deaths trding i ApOfoui* No. of Persons No. of IVuths 0,1 of. X-ray y was " ....... 3.901 1.124 615 315 3 licates 5,958 It is ce of ^ or Annual Lung Cancer Death Rates per 100,000 Man-Years of Kxjo-*ure jjj, yn,,,,, Proved I)res- ,4jH4...... id bv ;**}--- f this t the aving C&koown....... . Over*oll.. 44 IS 44 81 81 2102 2605 25 34 V due ^period. This would produce a rate of 69 s tic* per 100,000, again demonstrating the imition. jportance of these questionable, but un ited jproved, cases to the final conclusion, as to Jbecause, if there were no cases in this leath - jaumber of men with long exposure, and if ronic 'Ijsbestos is a carcinogenic agent, it must be nary included that these 240 men have demon lung. ijtrated considerable resistance. This is a bio war- ^logical phenomenon which has been observed nong '^previously and is consistent with the theory -4)f an intrinsic or endogenous factor in can- == leer. The only other explanation would be SlS ijthat the susceptible members of this age 3group bad died earlier of lung cancer. Table 18, which appears later in this section, iti- Taiu.k --Lung Cancer I tenths by Length of Employment NiiiiiIht of lVr.MiON ;nul Nuinlwr <>f Lung Cancer Death? lA`mrih of Employ tucm No. of Deaths No. of ----------------- *--------------- Persons Proved Total 5-0 ....... .. . *. 10*19.............................. 20-211....................... 30-311.............................. 40-40_______ 50+.................. 1.7U5 2.3W 22 Aa 1*5 55 o 1 :i s <> 0 n I 3 7 1 0 Totals............ 5,058 0 12 Annual hung Cancer Death Rates j>er 100,000 Man-Years of Exposure I.eturth of Employment Proved Total 5-9......................................... ............. 10-19............................ ........... 20-29......................................... 30-39......................................... ............... 40-49......................................... ............. 50+........................................... ............. 0 138 0 0 0 7 54 193 90 0 34 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, Tabi.e 10.--Lung Cancer Deaths by Exposure Category Number of Persons and Number of Lung Cancer Deaths Exposure Category No. of Deaths No. of --------------------- ---------------- Persons Proved Total 1................................ It................................ 111................................ Unknown..................... 2.031 2.150 1.772 5 4 3 2 0 4 4 4 o Totals............. 5,958 9 12 Annual Lung Cancer Death Rates per 100,000 Man-Years of Exposure Exposure Category , Proved Torn I........................................... .............. It...................... V................. lit........................................... Unknown............................... ............. Ovcr-uU.................. ............. 33 0 2.5 33 31 37 0 34 195# JjrrtMM--Truan 64.5 a. m. a. Akanrtis or industrial health LUNG CANCER IN AS: Table 11.--Number of Persons in Uarious Weighted Exposure Categories by Length of Employment Weighted Exposure Categories Employment I it hi 5-9 10-19 20-29 :w-:w 40-49 J0+ 707 598 490 603 8*3 861 314 303 243 347 218 137 76 67 41 24 21 10 Totals 3,031 Average years ol exposure 17 2,100 17Ji 1,772 16.6 known 0 1 2 l 1 0 5 29.0 Total 1,795 2.306 922 603 185 55 5,953 17.5 in which case the heaviest weighted ex posure (Category III) would show the shortest length of employment. Table II, which lists the number of persons in various exposure categories by length of employ ment indicates that this error has not oc curred. In fact, the average numl>er of years of employment for each exposure category is almost identical. Table 12, which develops the rates for smokers and nonsmokers, is most striking. It shows that not a single case of lung cancer developed among the 1265 non smokers and that all cases of lung cancer, both "proved" and "suspected," occurred in smokers. Table 12 was so striking that it was felt that further verification was necessary. It was possible that some abnormal distribu tion may have occurred, e. g., the non Table 13.--Number and Percentage Distribution of Smokers and Nonsmokers by 'Age Groups Age Group JHi........................... .. 45-54.............................. 55-64........................... .. 65+............................ ... Unknown............... .. Totals......... .. Averugo age............ .. Number Smoker Xonsmoker 3,200 896 411 164 2 -- 4.673 39J 669 224 202 150 0 -- 1,265 44.2 Unknown 12 4 2 1 1 -- 20 40.7 Percentugo Distribution Age Oroup Smoker Nonsmoker 20-44.............................. 45-54.............................. 55-64.............................. 95+................................ Unknown................... Total,............. 68.5 19.2 8.8 3.5 i -- 100% 54.5 17.7 16.0 11.8 0.0 -- 100% Unknown 60.0 20.0 10.0 5.0 5.0 100% lwss than 0.05%. Table 12.--Lung Cancer Death for Smokers ami Nonsmokers Table 15.--Number and l of Smokers and ` Exposure C Number of Persons ami Number of Lung Cancer fVjui* by Smoking Habits .. Nonsmokers....... . .. Unknown................. .. Totuls......... .. Persons 4,673 1,2*1$ 29 5.958 No. of Death* Proved 9 i\ 0 --- 9 Total o o 12 Exposure Calory * III.............................. i d Uinnk.n.o..w..n................... J i Totals....... A Tenure exposure category........-- NumN Sinokvr? l1,.*5953l 1.4254 4,673 2.0 Annual Lung Cancer Death Rates per 100.000 Man-Years of Exposure by Smoking Habits No. of Deaths ` - Proved Total ' Smokers................................... ............. Nonsnmkors.--,,................. ............. Unknown....................... ............. Over-all................... ............. 33 0 0 23 43 o it Percentage Dis:r; j Exposure A Category Smokers ... 1 n................ ... B 111.......................... 4| Unknown.. ...... 33.2 36.2 9 Touts........ ... -- 100% 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- Tabi.f. 14.--Number and Percentage Distribution of Smokers and Nonsmokers by Length of Employment Leticth of Employment 5-9.............................. . 10-19............................. . 20-29............................. . 30-39............................. . 40-49............................. . 50+............................... . Totals........... . Averaeo length of employment.-----. . Number Smokers Nonsmoki 1,408 1,967 722 433 110 33 -- 4.OT 377 426 199 166 75 22 - 1,205 17J> i9a 10 4 2 04 20 10.0 Percentage Distribution Length of Employment Smoker Nonsmoker 5-9... 10-19.. 20-29.. 30-39.. 40-49.. 50+... .. 30.1 .. 15.4 ... 9.3 29.8 33.7 15.7 13.1 5.9 1.8 Totals......... . !(!% ir% Unknowi 50.0 20.0 10.0 20.0 0.0 00 w% cerned, the smokers hac years less on the aver smokers. With longer ex age, one would expect group to show rtyigher were due to astystos. T the average exposure cr. the same for the two s this variable seems to t> in accounting tor this di The result of this ad that none of these factor the effect of Table 12. Comparison of the t with that of the Pravin. minion of Canada, and th in order to make a c exporieuce among asbeste of the general population Quebec, statistics were l earlier, in the office of Tabi.f. province Cohort Total Proved province (excluding asbestos workers) Number of Persons 1,193.000 * 5.923 f 1.192.000 In Oio rmvinre figures. It has twn Approximate miil|M>int of ihe e:u.: Bimtmphlcl. tNumber alive in cohort at be jinn: f>44 Dot. 17, June, 795.? -f Braun--Tman 4 jtt'A'G CAXCER IX ASBESTOS MIXERS {Table 15.--Xumber anti Percent,o/e Pistributnm of Smokers and Xoitsmokers by Exposure Caley, >ry eer Deaths JTEMjpeomsuorrye Total 1002 IViikiiuwft.. .. Totals. .ireniKo e|osure i;| x-aiegory............... Number Smokers Xunstnokcrs Unknown 1,533 1,691 1.425 4 4,673 2.0 44T542 1* 1,265 1.9 4 u a 3 Demography in the Provincial Ministry of 1 lealtli. 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 tor the years 1950 through 1955. In addition, all death certificates which specified primary cancer of llie lung, and all those which indicated lung cancer but did not specify the origin, were exam ined for the years 1952 through 1955. Man-Years Percentage Distribution saths Total a 0 0 M Exposure Citegory ' s 'f| ai.......................................... .. m............................ .. . Cnknown................. i Totals__ ... - Smokers 3H.2 30.5 100% Xonsmokers 37.5 35.7 26.7 0.1 100% Unknown 20J> 35J> 43jQ 0J> 100% denied, the smokers had worked about 2.3 larger uly, ad- 'pears less on the average than the non- re con- jiuokers. With longer exjiosure and greater smokers age, one would ex{>ect the nonsmoking employ- "jrroup to show a higher rate if lung cancer Ithqugh nere due to asbestos. Table 15 shows that do not d cases respect average |he average exposure category was almost -the same for the two groups. Therefore, jthis variable seems to be of no importance 'in accounting for this difference. ss than 1 The result of this additional analysis is shows filial none of these factors appears to lessen is eon- ;ihe effect of Table 12. if Comparison of the Cohort Experience Iribution yith that of the Province of Quebec. DoIth ^aiinion of Canada, and the United States.-- Table 16 gives a tabulation of the number of deaths from lung cancer in the Province and in the cohort for the years 1950 through 1955, and shows the annual rate per 100,000 in these segments. It will be noted from the table that the mortality rate for the "proved" cases in the cohort is only slightly higher than the rate for the Province. When the "suspected" cases are included in die calculation, the rale for the cohort rises to 33.8 per 1(X),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. Eor this reason, dcaown 4 2 04 20 Jin order to make a comparison of the experience among asbestos miners with lliat ; ;of the general population of the Province of .Quebec, statistics were gathered, as stated 'earlier, in the office of the Division of the vears 1954 and 1()55 were thought to be more nearly representative of actual condi tions. Even so, it is quite likely that the general imputation is not studied for lung cancer with the same diligence with which 1^ - Table 16.--Com[ari.sen of C.ohort wi.th Province of Quebec mb known KM) JOB B0.JO0 0.0 O__jO_ _ 00% *, 1958 j Number of Lung Cancer Death* Anmiul Kufo t*r Persons iwn 1051 1052 1933 1954 1935 Total lou.oou .. prov,,ince 1,198.000 196 220 245 303 303 337 1,024 ' Cohort J Total j Proved novlnce 5.923 t 3 t 2 2 0 0 3 2 i 1 32 12 9 1,192.000 193 218 245 300 302 354 1.612 ({eluding asbestos ,orIters) 22.5 33,8 23.3 22.5 t in {he Province figures. It lias lawn assumed all male liunr rancec ileatlis are for men of 20 +- years. Apprrulmalo midpoint of III* enumerated |>|Hiluttnn lur tuSI, arid tin estimated population tor 1911 (Kupport, l>lv. da la De* ai'irmplila). . I (Number alive In cohort at beginning of 1912. i --Trttan 645 '4 -S -v y-'-'di ftJM ^bfcMfi hf* - *K 4f! :^?n 7-3-1 'to# *0 ' $*r 4 :W J!iVl'j ,-*'! 1 A. M. A. A Returns OF INDUSTRIAL HEALTH 1J:XG CAW Age Group 20 44 45-64 55-64 05+ Totals Table 17.--f.tin<) Cancer Deaths for the Province of Quehee ' KMimatcd t population 777.t**i jri.oui 137,1 Ml !21.0> 1,237.100 Ntirr.b<r of Deaths i V4 ---- -Total Crrtlfli'd Total proved Total `rimary -Proved 17 13 n 9 67 30 43 29 1U0 3H tvu 32 111 33 6K 29 295 120 191 y9 Tola! I*.rrlifutl Ti.uil Proved 17 9 Mt 35 117 57 14H 54 342 155 Sirnftml l''rint.-iry Total Proved 17 9 56 32 116 57 148 54 337 152 Table the l Age Group 2ti 41 . . 45 M............ 55-04............ 65+ ------ Total........... Rapport, 1954. Age Group 20-44........ ...................... .. 45-54...................................... ................ 55-64........................................ ............... M+......................................... ................ Over-all................................ ............... Death Rates per 100,000 1954 Total Certified Specified Primary Total 2.2 314.2 73.0 91.7 Proved 1.7 17.H 27.7 27.3 Total 1.4 21.3 50.4 56.2 Proved 1.2 14.4 23.4 24.0 23.8 9.7 15.4 8.0 1955 Total Certified To till Proved 2.2 29.7 85.4 13SL3 12 17.3 41.6 44.6 27.6 12.5 Specified Primary Total Proved 2.2 27.7 84.7 122.3 1.3 15 S 41.6 44.6 27.2 123 * Data from death rcrtlfiits. f Estimate /or population obtained by applying 1951 percentages for uge groups for mules to tho total imputation for 1954, as gtn In Rapport, Piv. tie la Pornographic. .* 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-sjiecific 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 two 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 ljetween the age-specific rates shown in Table 17, and those for the cohort, shown in Table 8. An average of the 1954 and 1955 rates for the Province has been used, since the 1955 figure was higher and may have been ex ceptional. This comparison, summarized in Table 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 1935 figures for the Province. It is true that, in the case of the age group of 65 ami over, the five deaths provide a figure which is almost significant at the 95(/`o 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 thaCthe exact cause of death in the very old is not Table 18.--Comparison of the Actiuil and Expected Number of Lung Cancer Deaths by Ape Among Asbestos Miners Age Group Provlmn Total S|HM-llh*t| lTimarv Rato per lUO.OUO 20-44 45-54 55-64 s+ Unknown 1.8 21.5 67.6 b9.3 ** OhsrrvH \0< Expected No. of No. of <d Deaths Miners Deaths* Proved Total" 3,901 1,124 615 315 3 0f 2 ! \ 2 2 l1 .. 0 o Tl*4M*cti`l imtnlx'r Is Ikin* l on the average of the 1951 lnrf 1955 nge-sfvWfit* ruti-s for tin* Provimi* of Quoboc. a t Actually 0.4. a matter of as it is in y< Table IS viously raise of the cohort cer at an age iationr and th ; be offered f in 240 men employment Before le; Province wi shown that i I sonably the - ' be observed It should : t retire and cj that the ohk i the genera! in Table 2(; rate generall; fore, we cov over 65 to r group betweto the oldes that by usin. tion, we ha\ eral popular than if we people in the A compari and the por whole was : from severa. lips 79 gave Canada for 1952. The Table 20. These figv in rates bet 646 Vol. IT, June. I05S Braun--Truan \ t 'UAL HEALTH 4 LUNG CASTER IX AGBb.STOS MIXERS a Table \9.--Age Distribution of Adult Mules for Tahle 20.--Amuutl Death Rates per 100,000 for the Province of Quebec, 1951 * ________ Cancer of the Lung in Canada* Province Groups ol Years Specified Prisnarv Tool 17 56 116 146 Proved 33 67 54. 337 153 Afe Orotip . NumU r -H....................... 45-54....................... 55-64....................... .......................- A Total........... 727.135 188,952 128,944 113,467 1,158,496 ' Rapport, 1954. 63 16 1110 as it is in younger persons. in t'olmrl Till Hi 10 5 -- 100 \ interest Avv Group rtwirr 3o 30-34 35-39 40-44 *5-49 50-54 55-59 60-64 65-69 70-74 75-79 SO-84 S5+ All Ages Hrtl 1933 0.2 0.9 2.0 ~ 3.0 5.2 8.2 12.7 12.5 15.1 10.7 15.8 8.2 11.4 2.8 1941-1943 0.3 0.9 3.2 5.4 12.5 1H.9 27.0 33.7 34.5 30.6 30.0 27.9 14.3 7.1 1950-1952 1.0 0.8 3.0 6.5 16.7 37.2 59.7 77.8 102.9 86.3 83.9 59.7 71.0 15.8 Specified Primary Total 13 37.7 84.7 123.3 Proved 1.3 15.1 41.6 41.6 Table 18 also answers a question pre viously raised. It shows that the members of the cohort have not died from lung can^cer at an age earlier than the general popu lation, ami that such an explanation cannot "Mortality from 1ung Cancer In Canada,** 193! to 1952. increase is particularly marked after age 50, confirming an observation previously made, to the effect that until recently lung 37.3 1U Ibe offered for the absence of lung cancer cancer has probably been underdiagnosed |in 240_men with more than 40 years of in the older age groups in the general popu Oloa tor 1954, ms *tv*u Employment referred to on jsigc 64.1. lation. ^ Before leaving this comparison of the To use these figures for purposes of rized in Table Province with the miners, it should be 5cd number of shown that their age distributions are rea iot significantly sonably the same. That this is the case can mber of deaths. ibe observed from Table 19. 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 eacli 1954 and 1955 1 It should be remembered that the miners age group for the years indicated is not is true that, in ^retire and consequently, it can be expected known, this must be an approximation. >f 65 and over, that the oldest age group will be larger in However, the rates would be somewhat as figure which is Ithe general population. The data presented follows: % level. How- ^in Table 20 indicate that the lung cancer iat this number rate generally decreases after age 70. There Id but unproved . Furthermore, e rate for the rstated in this 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 !;o the oldest group of miners. It is felt reason that the I that by using the whole adult male popula very old is not tion, we have developed rates for the gen eral population which are somewhat lower Age Group 20-44 45-54 55-64 654- Rate S 27 69 ' 90-95 These rates are, in general, lower than those developed for the total (proved and suspected) cases of lung cancer among the asbestos miners. The only large difference, however, is in the age group of 65 years and the Actual and mg Cancer nong 'S than if we had been able to exclude the people in the general population over 75. 1 A comparison between the asbestos miners Jjand the population of the Dominion as a 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). Observed No. jKetedot Deaths oaths Proved .Total Ot 1 1 3 1] l* *4 35 - 00 jwhole was made, using statistical material from several sources. In one source, Phil lips 79 gave age- and sex-specific rates for JCanada for three periods between 1931 and 1952. The rates for males are given in Table 20. . 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* averare of the 1954 and Quebec. These figures show strikingly the increase with 25.3 per 100.000 for proved cases and in rates between 1931 and 1952, and this 33.8 per 100,000 for total cases among the 647 1 /.r.Yt; ('AWTA. i. m. j. Altunins nr ixih\stkial health Iahi.k 21.--Number of Deaths and Death Kates per HH)pOO by Aye Unatps far the . \dnlt Male Population of the United States* way, and other countries, at least 50,000 persons must be exposed throughout the world, and it can be assumed that this Aw Group 21)-M 55-64 65+ Tom! Population 24,M4. ,340,000 5,i7o.om* 44,610,000 Cases Hhlt 2.9T0 i,2*4 t>, ISt Kate per HW.UOO :$r.n 1tHW..3ti 37.2 Data from "Vital Statistic* of Uto UiuUmI States,' Vol. 1 and 2, 1952. asbestos miners in this study. It is there number has been fairly constant in the 20 years *ince 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 4j .K\f.rkihMt l"lflr < VfWf V' t\..; j* KPlrKohvtimSvHomf QMuotVuru-.* I F/mincp *>f QuWwe l**ss **ulj:uvnt*' tturuto* Muiuiv.il ot Isle ii* Jt' I* It is assume! :h:u . fore obvious that there are no important gives a rate of 15 per 100,000, which is at- immediately sur differences between the rates for asbestos least indicative that any lung cancer rate ducing areas is j miners and those for the general population which can l>e calculated for workers ex of eight countii of QucIk'C and the Dominion of 1`anada. posed to asbestos dust is not much greater While Megantic Since it is probable that figures for the than that for the uuexposcd population. twice that of t! United States are more complete and, there Comparison Between Eight Counties Ad countiesj if is k fore, possibly more comparable to the data jacent to the Asbestos-Producing Areas and : Province, and c for the miners, age-specific rates were com Eight Selected Counties.--To compare lung t rate for Montre; puted from "Vital Statistics of the United States,''Volumes f and If. for 1952. These cancer mortality rates in the counties sur rounding the asbestos-producing areas with ji would certainl-v 1 very low muni* rates have been tabulated in Table 21. another group of counties in which no as | 1950 and 1951. It is apparent that these rates compare bestos miners are likely to reside, the rates in those years sc favorably with those for the asbestos miners were computed on the basis of figures for undoubtedly beer as shown in Table 8. Still other rates tor the United States were obtained from the American Cancer Society, and tor males, these were 25.3 per 100.000 in 1953. and the years 1950 through 1955. The eight counties selected for comparison were Argenteuil, Chateaugay, Montniagny, Portneuf, Kichlieii. Rivicre-du-i .oup, St. Iother years. 195C expected to be | won id result in j The only pos 28.0 per 100.01)0 in 1955. They are not llyacinthe. and Terrebonne, mainly because i compari.son" i.s t.lr identical with the rate calculated from the they represent a wide geographic distribu the persons who figures of the office of Vital Statistics, but tion throughout the Province. The counties ties surrounding this is possibly because the American Can selected because of their proximity to the bestos-producing cer Society rates are for males of ail ages. asbestos mines include Arthabaska, Eeauce, incidence of lur. Nevertheless, they, too, compare favorably Drummond. Kmntennc, Megantic, Rich live elsewhere in with the rates 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 mond. Sherbrooke, and Wolfe. Table 22 shows the number of lung cancer deaths for the years 1950 through 1955 for each of these counties, and a mortality rate, Ctiinuii^t on . Loses. T^:ng on tos Milters.--Ah tion of all the kr. or another (as distinguished from the gen based on the adult male population in 1952. cancer of the lu eral population groups just discused. who To emphasize the comparison, Megantic particular value : have no exposure) an interesting observa County has been shown separately, as has view, it is of ir. tion can lc developed by deduction. IIne the Province of Quebec and also the Prov cases for the reco per88 has stated that there are about 35.000 ince with the eight "asbestos-producing'' prior to the beg- persons exposed in the United States, and counties subtracted. Because of its unique covered by the sti: we have found that the Canadian mines lung cancer death rate, Montreal et Isle de the diagnosis wa employ about 8000. Elsewhere, it has been Jesus has also been listed in order to provide coma. During th estimated that the workers in l'.ngland who 1 further comparison. investigation, the: have exposure total between 3000 and 5000. It is apparent from the table that the and three susjh-i With workers in Africa, Denmark. Nor-. lung cancer death rate for the eight counties Through 1956 m were eight deaths. 648 l ol. 17, June, l'j>$ promt--Triton RIAL HEALTH | LUXG CAXCER IN ASBESTOS MIXERS . :t least 50,000 Tabi.k 22.--Xumber of l.uufi lamer l>entli.r unit Rale fer IO/i.l>in> Man-Years throughout the umed that this istant in the 20 c first case of was reported, rs of exposure and this figure roximately 450 asbestosis re- Count les Mule Iahk ('.mm iVntlis * Adult Malt* - r<>|mlntl<>n 1952 1050 1951 1952 1953 1954 1955 County 7Kltftit "Atljamit'* i;ui :t 1. t a a3 y W* 11 1 111 iKltfht ('ount U*3 sit.niftt 2m A Is y i province of Qurtn'C M98.IXXI l!H 220 215 3U3 :nut 357 4 province of gurW'c lew eight AI M'*oantlrJe;aKlvcntlMIseleutinetUJessus I'Wn.nnfl 190 217 287 2W .Ml 394.000 7 158 192 185 225 * It is Assumed that all male Inns cancer deaths occurred after aye 20. , Total 15 54 49 11.21 157ft 770 H.m* pr lUO.UBl ivy 9.4 9.8 22.0 2:i. 32.3 period. This immediately surrounding the asbestos-proXX), which is at facing areas is practically identical with that ing cancer rate . 0f eight counties selected for comparison. >r workers ex- ; While Megantic County has a rate nearly >t much greater j twice that of the combined eight selected d population. 1 counties, it is lower than the rate for the it Counties Ad- 3 Province, and considerably lower than the icing Areas ana Irate for Montreal. The figure for Montreal o compare lung ! would certainly be higher except for the e counties sur- 1very low numbers of deaths reported for cing areas with '1950 and 1951, and it would appear that n which no as- Jin those years some error in reporting has eside, the rates 3 undoubtedly been made. On the basis of the of figures for jother years, 1950 and 1951 deaths would be `55. The eight Jexpected to be about 200 greater. This rison were Ar- :*would result in a rate of 40 per 100,000. tmagny. Port- j The only' possible conclusion from this du-Loup, Sr 'comparison is that there is no evidence that mainly bccau-e jthe persons who live and work in the counaphic distribu- fties surrounding and adjacent to the as The counties Jbestos-producing areas have any greater oximity to the !incidence of lung cancer than those who ibaska, Bcaucc, 4 live elsewhere in the Province, egantic, Rich- ] Comment on All Rccofded Lung Cancer *lfe. Table 22 -Cases, Living and Dead, among the Asbescancer deauu tos Miners.--Although a simple enumera1955 for each Jtion of all the known or suspected cases of mortality .rate, jeancer of the lung in these areas has no ilation in 1952. ^particular value from a statistical point of son, Megantic Jview, it is of interest to summarize such irately, as has jcases for the record. There were nine deaths also the Pmv- iPr'or ,(> l*u' loginning of die time period tos-producino-" 1 covered by the study, including one in which of its unique ;^e diagnosis was mediastinal Ivmphosarreal et Isle d* lcoma- During the period covered by this rder to provide !invcstiSntion- t!u're wer ninc Provc><1 rases ]and three suspected cases in the cohort. table that the !Through 195b and to date in 1957, there eight counties i"Tre ei&}lt <loat,,s' six of w}lich " crc 'merely L IT, June, 195S ^ra''-Trmn 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 arc now living four cases in which the diagnostic evidence is strongly suggestive of lung cancer. This is a total of 33 cases of all tyj.es, including 10 "sus pected" but unproved cases, and 4 that are still living. The remaining 19 constitute the total of proved cases of cancer of the lung among the asbestos miners since 1940. The proved cases averaged 59 years of age at death, and varied between 37 years and 68 years. Their working span covered periods varying from a minimum of 14 years to a maximum of 37 years. Only three men had less than 25 years of em ployment in the industry'. Seven among those on whom such information is avail able had a weighted exposure placing them in Category' III, and six worked in an exposure represented by Category I. There were only 17 among these proved 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 649 A. M. A. ARCHlms Ol: IXIH'STRIAI. HEALTH I.C.XC CAXCER /.' and exposure to asbestos has been evident since the report in 19.55 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 mainauthors, although some workers considered the correlation to be inconclusive. The pres ent study was undertaken in an effort to de termine whether a causa! relationship did, in fact, exist between exiosure 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 industryin 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 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 650 was not possible to trace 1.5.5 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 lx? strongly suggested iii 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 likelv that such cases would not le 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 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 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 if 37.2, 25.3, ami 2 sources for adult m Finally, in this n: would appear that t of persons ex[Kiw worse with resjx-vt of the unexjKised p* The counties su producing areas, i: most of the asbest most identical murt: } sight counties wide Province, and are 1 remainder of the P than the rate for M Since 1940 .there which the diagnosis the lung may be c proved. ApproximT; were associated with died in the recogntz least une-third had posure (Category I On the basis os complete and reliab! j^conclude that the . Province of Quebec jicantiy higher death than do comparable population. Furthermore, the cancer in the areas c tos operations is com widely scattered thr<> jOttelx.-c and is lout. Sized areas within the refe: 1. Alascio Escobar, fReview of 200 Cases. J (.'0:375-37 (Sept.) ViC 2. Allen, M. L.: Brot tiH'iateil witti Pncinr.ui Cases, J. Indust. Hy-_r. It 3. Cartier, 1'.: A C. >f Asliesto-is, ArcA. r i'49. 4. Amler-on, C. S, aj aid Carcinoma of die f ! March) lu.tx. 5. Itaailcr,- H. W.; A jW'chnschr. f5:407-4fls t 1\>I. 17, June, in# \Sratui--TriwH I-TALTH -U'-VG CANCER IX ASBESTOS MIXERS |,)f 37.2, 25.3, and 28.0obtaiiu.il from various cse for It. Belli ms, \V.: Kx|ieriiuetital Asliestosis, naming 'jourccs for adult males in the United States. Schweiz. Ztschr. allg. Path. 14:275-297, 1951. n 1955 `Finally, in this matter of coni[arison, it 7. Behrens, \V., Jr.: The Clinical Picture and Pathology of Asbestosis, Ztsehr. Unfallmed. u. i cancer \ould appear that the world-wide experience Bertifskrankli. 45:129-140 (June 15) 1952. - been jf persons exposed to aslwstos dust is nut 8. llerhlinger, \V.: Increase of Lung Cancer rongly jivorse with resjx'ct to lung cancer than that and Diseases Due to Dust Inhalation, Med. Klin. tudied vtnent, c, and 1 that ion of /-four an 45 been Thirty which d ex- Jof the unex|x).sed population. 1 The counties surrounding the asbestos- 'producing areas, in which it is presumed puost of the asbestos miners live, have al most identical mortality rates with those of fight counties widely scattered through the Province, and are lower than those for the ^remainder of the Province, and much lower ^ihan the rate for Montreal. | Since 1940 there have been 19 cases in dtfhich the diagnosis of primary cancer of :he lung may be considered to have been proved. Approximately half of these cases 27:1547-1442 (Sept. 11) 1941. 9. Bcrentilum, I.: Irritation and Carcinogenesis, Arch. Path. 58:254-244 (Oct.) 1944. 10. 1'ohtve: Asbestosis, Deutsche tried. Wchnschr. 62:928-950 (June 5) 1936. 11. Bohme, A.: Results of Periodical Examina tions of Workers in an Asbestos Factory, Beitr. Silikose Forsch. 11:54, 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. 15. Rreslow, L.; Hoaglin. L.; Rasmussen, G., and Abrams, H. K.: Occupations and Cigarette Smoking as Factors in Lung Cancer, Am. J. *r, as Vere associated with asbestosis. All but one wed" lied in the recognized "caneer-age" and at 100,- 'east one-third had only the lightest exwere -iosure (Category I) to asbestos dust. rose On the basis of what are believed to be Tub. Health. 44:171-181 (Feb.) 1954. 14. Bristol, L. J.: Roentgenologic As[>ccts of Silicosis and Asbestosis, A. M. A. Arch. Indust. Health 11:189-195 (March) 1955. 15. Cancer of the Lung: An Evaluation of the Problem, Proceedings of the Scientific-- Section, ected hWiplete and reliable data, it seems fair to Annual Meeting, American Cancer Society, Inc., these vonclude that the asbestos miners in the Nov. 3-4, 1953, New York, American Cancer | !ikely province of Quebec do not have a signif Society, Inc., 1956. | j d in icantly higher death rate from lung earner 1 and lark- jiait do comparable segments of i 'population. * the general 16. Cartier. I'.: Asbestosis Cancer of the Lung, in discussion on Smith, W. K.: Survey of Some Current British and European Studies of Occupa tional Tumor, Problems, A. M. A. Arch. Iudust. Furthermore, the death rate from lung Hyg. 5:262-263, 1952. tI j -udy, j does ncer in the areas contiguous to the asbes 17. Cartier, P.: Some Clinical Observations of tos operations is comparable to that in areas Asbestosis in Mine and Mill Workers, A. M. A. widely scattered throughout the Province of Arch. 1 ndtist. Health 11:204-207 (March) 1955. 1 ex- `Oueltec and is lower than in some urban- 18. Clerens, J.: Research into Pulmonary Asbes | fact Jr lied areas within the Province. tosis in Belgium, Arch, beiges nied. Sociale 8:557 (i the REFERENCES 565 (Nov.) 1951. 19. Clynes: Asbestosis and Silicosis, Brit. M. J. | ` the 1. Alascio Escobar, R.: Bronchial Carcinoma: 1:379, 1931. ! seg- Review of 200 Cases, J. Intemat. Coll. Surgeons 20. Collin, G. J.; Duryee, H. C.; Maier, H. C.; i ipur of J&:375-379 (Sept.) 1956. ;j 2 Allen, M. L.: Bronchiogenic Carcinoma As sociated with l'ncuinoiiocnninsi.s: Rejvirt of 2 Pardee, H. E. B., and Wyntcr, E. L.: The Effects of Tobacco Smoking, Panel Meeting, Bull. New' York Arad. Med. 32:133-156 (Feb.) 1956. ; ntly uses, J. Indust. Hyg. 16:346-547 (N'ov.) 1044. 21. Cohart, K. M.: Lung Cancer and Economic | rate ] 3. Cartier, P.: A Contribution to the Study Status, Cancer 8:1126-1129 (Nov.-Dee.) 1955. | iers \i Asbestosis, Arch, ittal. profess. 10:589-595, 22. Cooke, W. E.: Pulmonary Asbestosis, Brit. j the $449. M. J. 2:1024-1025 (Dec. 3) 1927. I the | 4. Anderson, C. S., and Dilde, J. 11.: Silicosis 23. Cureton, R. J. R.: Squamous Cell Carcinoma i lult aid Carcinoma of tlie I.ung, J. Hyg. 38:185-204 (March) 19J8. Occurring in Asliestosis of the Lung, Brit. J. Cancer 2:249-253 (Sept.) 1948. i ida. j 5. Baadcr/ K. \V.: Asbestosis, Deutsche mcd. 24. Cutler, S. J.; Sdmcidermaii, M. A., and \ ttes j,Vcbnschr. 65:407-408 (March 17) 1959. Greenhouse, S. W.: Some Statistical Considcra- I 195? jpcintn--Triton \ 651 Hi A. M. A. ARam r.s or ixnrsmiAi. uhauh Li'Xi; c.i i J lions in the Study of Cancer in Industry, Ain. J. 41. (ilovnr. S. K.: l'm'iiiiiixonio-is: A Hijtr,- l'uti. Health 44:1159-1106 (Sept.) 1054. logical Survey ol Necropsy Material in 1205 Case, Health Mm: No. 452. U I 25. Davies, D. I'.: Current Status of Lung Lancet 1:810-814 (April 14) 1951. ' Cancer Research: Sonic Pathogenetic Aspects, 42. Gloyne, S. R.: A Case of Oat-Cell Car 59. Huvper Cancer of 1 $ CA 6:169-174 (Sept.) 1956. cinoma of the Lung OiVurring in Aslx'st.rsi* Dis. Clicsi 26. Dcsmculcs. R.; Rousseau, 1..; Giroux, M., TuLtcIc 18:100-101 (Dec.) l"3b. .' (41. Issell.;. and Sirois, A.: Aslx-stosis and Pulmonary Cancer, 43. Gloyne. S. K., and Mcrewclhcr, E. R. \ H. I-: A si s Scinainc dc. hop. Paris 2.1:1820-182.1 (Aug. 7) Aslx-slos, Occupation and Health, Supplement to Reiiort of ( 1947. Encyclopedia on Occupation and Health, Geneva, Available L 27. Doll, K.: Bronchial Carcinoma: Incidence international Labor Office, 1938. (Nov.) 1955 and Aetiology (Milroy Lectures, abridged), Brit. 44. Goldblatt, M. W., and Goldblatr, J.; jr_ 61. Kenu.v M. J. 2:521-527 (Sept. 5); 585-590 (Sept. 12) dustrial Carcinogenesis and Toxicology, in Study of tl: 1953. dust rial Medicine and Hygiene, edited by K. \ aiul Lary nx, 28. Doll, R.: Mortality from Lung Cancer Mcrewetlier, London, London, Lutterworth- (c 62. Kenna-, Among Asbestos Workers, Brit. J. Indust. Med. Co., Ltd., 1956, Vol. 3, pp. 185-188. Studies of I- 12:81-86, 1955. 45. Ilaenszel, W. M.: Epidemiological Tests o; Larynx, Bri: 29. Donnelly, J.: Pulmonary Aslx-stosis, Am. J. , Theories on Lung Canecr Etiology, Pub. Health 63. Klotz, Puli. Health 23:1275-1281 (Dec.) 19.1.1. Rep. 71:163-172 (Feb.) 1956. ` - Carci^nui o; 30. Dorn, H. F., and Cutler, S. J.: Morbidity 46. Hammond, E. C.: Lung Cancer and Com (Jar s*1939* from Cancer in the United States, Pub. Health mon Inhalants, Cancer 7:1100-1108 (Nov.) '/o; 6-t!jLanza, Monograph No. P. II. S. Publication No. 418, 47. Uanmioml, E. C.: Etiology of Bronchioger.ir I. W.: The :Uf U. S. Public Health Service, 1955, 121 pp. Carcinoma, CA 6:156-168 (Sept.) 1936. Dust on the y 31. Dorn, II. I'.: Cancer Morbidity Surveys: A 48. Hollcb, II. R., and Angrist, A.: Bronchi,-., liminarv Stud 1!! Tool for Testing Theories of Cancer Etiology, genic Carcinoma in Association with Pulmon-.-- 1935. Am. J. Pul.. Health 45:615-621 (May) 1955. Aslx-stosis: Ke|M>rt of 2 Cases, Am. f. Path js". 32. Egbert, D. S., and Geiger, A. J.: Pulmonary 123-135 (Jau.) 1942. '` 65. I.anza, New York an Asbestosis and Carcinoma: Report of a Case with 49. Homburgcr, F.: The Co-Incidence of 1938. Necropsy Findings, Am. Rev. Tuberc. 34:143-150 Primary Carcinoma of Lungs and Pulmonary 66. Lew, E (July) 1936. Asbestosis: Analysis of Literature and Report pane Records 33. Ellman, P.: Pulmonary Asbestosis: Its of 2 Cases, Am. J. Path. 19:797-807 (Sept.) 1043 Indii't. Hyg. Clinical, Radiological, and Pathological Features 50. Horn, D.: Is Lung Cancer on the Increase1 67. Linzbac -4 'i and Associated Risk of Tuberculosis Infection, Evaluation of Present Day Evidence: Cancer of pational Cane J. Indust. Hyg. 15:165-183 (July) 1933. the Lung. Proceedings of the Scientific Sccta^ , path. Anar. 5 34. Ellman, P.: Pulmonary Asbestosis, Proc. Annual Meeting. American C.uicer Societv Jnr 68. I.yncli, Roy. Soc. Med. 34:557 (July) 1941. Nov. 3-4, 1953. "' nionary Ash 35. Fed, A.: Pneumoconiosis in Asbestos 51. Honiig, F.: Clinical Considerations the Asliesto-Silico; Workers, Presse med. 39:1872-1874 (Dec. 19) Question of Industrial Cancer of Asliesros Work 1935. 1931. ers, Ztschr. Krebs forsell. 47:2Sl-287, 102S. 69. Lynch, 36. Fulton, W. B.; Dooley, A.; Matthews, 52. 11ueper, W. C.: Cancer in Its Relation to nionary Aslies J. L., and Houtz, R. L.: Asbestosis: Part III. Occupation and Environment, Bull. Am. Sr - cinotna and E The Effects of Exposure to Dust Encountered Control Cancer 25:63-69 (June) 1943. 36:567-573 (A in Asbestos Fabricating Plants on the Health of a Group of Workers, Special Bulletin No. 42, Pennsylvania Department of Labor and Industry'. Bureau of Indust. Standards, Sept. 20, 1935. 37. Gardner, L. U., ami Cummings, D. E.: Studies on Experimental Pneumoconiosis: Inhala tion of Asbestos Dust; Its Effect upon Primary Tuberculous Infection, J. Indust. Ilvg. 13:65-81 (Feb.); 97 (March) 1931. ' 53. Ilneper, W. C.: Significance of Industri-,; Cancer in the Problem of Cancer, Occup Moi 2:190-200 (Sept.) 1946. '` ` 54. Huciier, W. C.: Environmental and Occup-. tional Cancer, Public Health Service. Supp. 'tv, U. S. Public Health Service, 1949. 53. HiK-por. W. C.: A Methodology for Envirtfl. mental ami (iccupational Cancer Survcvs, plfi.rllcallli Monograph No. 1, P. IT. S. Public;,,;,^ 70. Lynch, i tosis: Analysis 14:874-889 (X 71. McPhee: of Employees Indtist. Hyg. 72. Merewet Pulmonary Ed 38. Gillbuii, A. (: Mortality Trends in f.tiug No, 12, l . S. Public Hc.dtb Service, 1950. Cancer, Cancer 8:1130-1136 (Nov.-Dee.) 1955. 56. 1 Iuc]>cr, W. C.: Environmental Lu-~ tioits in As]*v P>8 ( May) ; A 39. Gilliam, A. G.: Mortality Attributed to Canccr. ludust. Med. 20:49-62 (Feb.) 1951. ' 73. Merewet; Lung Cancer in the Large Cities of the United States in 1948 and 1949, J. Nat. Cancer Inst. 15:1307-1312, 1955. . 57. Iluejier, W. C.: Occupational and Envirrc.mental Pulmonary Cancers with Social Rcferer. t to Piictimix'i miosis, Prixecdings, 7tli Sarar-- Report on F.ffe and Dust Sup; London, His 3 40. Gloyne, S. R.: Two Cases of Srpuunous Synnxisium on Pneumixamiosis, 1952. - 74. Merewet! Carcinoma of the Lung Occurring in AsU-losis, 58. I litcjx-r, W. C.: A (Jucst into the Envirr,. Aslx-stosis,. Tl: Tubercle 17:5-10 (Oct.) 1935. mental Causes of Cancer of the Lung, put. 152 1 Jan.) 19c 652 I ol. 17, June, /r.n promt--7V,ijk si* A ... -s-T-'--r- ____ I . j`" .Til 1 LL'XU C.iXCUR IX .tSRESTOS MIXERS >sto>ses, Health Monograph Nro. .16, I*. II. S. Publication N<>. 45-, U. S. Public Health Service, 1**35. 59. lluepcr, \V. C.: Environmental Causes of -ar- -i Cancer of the Lung other than Tobacco Smoke, >sis, ; Dis. I host. 30:141-158 (Aug.) 1**56. 00. Isselbacher, K. J.; Klaus, 1I,, ami Hardy, ^ i If. I..: Asbestosis ami Bronchogenic Carcinoma: Report of One Autopsied ( ase and Review of -va, * Available Literature, Am. I. Med. 15:721-732 A t.Vov.) 1953. ' In- j tl. Kennaway, E. L., and Kcnnaway. X. M.: A JIn- Study of the Incidence of Cancer of the Lung A. ami Larynx, J. Hvg. 36:236-267 (Tune) 1956. & 02. Kennaway, E. L., and Kcnnaway. X. M.: Studies of Incidence of Cancer of the Lung and o{ J Larynx. Brit. J. Cancer 5:153-138 (June) 1951. 4th j <i3. Klot/, M. O.: Association of Silicosis and Carcinoma of the Lung, Am. J. Cancer 35:38-49 an- (Jan.) 1939. *54. -i 64. Lanza, A. J.; McConnell, W. J., and Fehnet, nic j /. W.: The Effects of the Iuhalatiuu of Asliestos Dust on the Lungs of Asbestos Workers: Pre -10- liminary Study, Pub. Health Rep. 30:1-12 ( Ian. 4) irv 1935. ' 18': 65. I .an/a, A. J., editor: Silicosis and A>U-stosis, i Xew York and London, Oxford University Press, of 1938. try 66. Lew, E. A.: Use of Life Insurance Com o pany Records for Cancer Studies, A. M. A. Arch. '43. Indust. Hyg. 5:198-203 (March) 1952. :e? 67. Lin/.bach, A. J., and Wedler, II. \\ .: (<cettof pational Cancer among Asbestos Workers, .Arch, on, . path. Anar. 307:387-409, 1941. tc., i-A (sS. Lynch, K. M., monary Aslicstosis: and Smith, Carcinoma W. of A.: Pul Lung in .he AsU-sto-Silicosis, Am. J. Cancer 24:56-64 (May) k- ; 1933. 69. Lynch, K. M., and Smith, W. A.: Pul to monary Asbestosis: A Report of Bronchial Car oc. ;; cinoma and Epithelial Metaplasia, Am. J. -Cancer 36:567-573 (Aug.) 193'). ial ` 70. Lynch, K. M., and Cannon, W. M.: Asbes M. tosis : Analysis of 40 Xeeropsied Cases, Dis. Chest 14:874-889 (Xov.-Dec.) 1948. a 71. McPiicetcrs, S. B.: A Survey of a Group i of Employees Ex poser1 to Asbestos Dust, J. i Indust. Hyg.-18:229-239 (April) 1936. ln- 72. Merewet her, E. R. A.: The Occurrence of lie Pulmonary Fibrosis and Other Pulmonary Affec on '; tions in Astwsios Workers, J. Indust. Hyg. 12: i-o< 198 (May); 239 (June) 1930. ' 73. Merewcther, E. R. A., and Price, C. W.: Report on Effects of Asliestos Dust on the Lungs nee-:*i ae*-| and Dust Suppression Loudon, His Majesty's in the AsU-stos Industry, Stationery Office, 1930. /4. Merewcther, E. R. A.: A Memorandum oil n- 3 A'U-stosis. Tulicrrlc 15:10*7; (Dee.) 1**33; 15: b. 152 (Jan.) 1934. ^ .j prtnm--Trnan 75. Merewcther. K. K. A.: Annual I\c|H>rls of the t hief Inspector of Factories. Loudon, His Majesty's Stationery Office, 1947. 76. Merewcther, ]'.. R. A., editor: Industrial Medicine and Hygiene, London, Hutterworth & Co., Ltd., 1956, \ ol. 3. 77. Xnrdmauti, M.: The Industrial Cancer of Workers in Asliestos, Ztsehr. Krelisforeh. 47:288 302, 1*158. 78. Xordmann, M., and Surge. A.: 1`ulnumary Cancer Produced by Asliestos Dust in Experi mental Animals, Ztsehr. Krelisforeh. 51 :168-182, PHI. 79. Phillips, A. J.: Mortality from l ancer of the Lung in Canada (1931-1952), Caitad. M. A. J. 71:242-244 (Sept.) 1954. ' 80. San|ic, K.: Further Contribution- i< the Roentgenological Diagnosis of Asbestosis, Arch. Gewerbepnth. u. Gewcrbehyg. 9:391-406. 1939. SI. Smith. K. W.: Pulmonary Disability in Asbestos Workers, A. M. A. Arrh. Indust. Health 12:1**8-203 (Aug.) 1955. 82. Smith. L. W.: Pnctimocniiio-is and Lung t amer with S|H-eial Reference to Siheo-i-. ami Asbestosis, Cumpeus. Med. 2:3-10 i Xm, I 194'*. 83. Smith, W. E.: Survey ot Some Current British and European Studies of Occupational Tumor Problems: Part III. AsU-stos, A. M. A. Arch. Indust. Hyg. 5:242-263 (March I 1932. 84. Stull. R.; Bass, K., and Angrist, A.: Asbestosis Associated with Bronchogenic Car cinoma, A. M. A. Arch. Iut. Med. 88:831-834 (Dee.) 10.51. 85. Telcky, I..: Occupational l.img lancer, Aela Union internal, coutrc Cancer 3:253-273. 1**38; also, Zeutrallil. Gcwerbchyg. 27:33. 1**40. 86. Vorwald, A. J.; Durban, T. M.. and Pratt, P. C.: Experimental Studies of AsU-stosis, A. M. A. Arch. Indust. Hyg. 3:1-43 .Jan.) 1951. 87. Wedler, II. W.: Asbestosis and Lung Cancer. Deutsche mcd. Welmsehr. 6*> :575-576 (Aug. (i) 1*743. 88. Wegelius, C.: Changes in the Lungs in 126 Cases of Asliestosis Observed in Finland, Acta radiol. 28:139-152, 1947. 89. Werbcr, M.: Pulmonary Asbestosis Asso ciated with Carcinoma, ZentralM. Arlieitsmed. u. Arbeitsschutz 2:179-180 (Xov.) 1952. 90. Wood, W. B., and Gloynr, S. R.: Pulmonary Asbestosis Complicated by Pulmonary TuU-reulosis, Lancet 2:954-956 (Oet. 31) 1931, 91. Wyers, H.: Asbestosis, Postgrad. Med. 25: 631-638 (Dec.) 1949. 92. Wynder. E. L., and Graham. E. A.: Etiologic Factors in Brondtiogeuic Carcinoma with Special Reference to Industrial .Exposures; Rciiort of 857 Proved liases, A. M. A. Arch. Indust. Hyg. 4:221-235 (Sept.) 1951. 653 d:l i1 if ' 4I WJU I, '.. 9'TJr* S1 m-