Document 2jOrJb780zr7ZQ4Eg98BxqNkb

A. M. A. ARCftHE S OF IXDCSTRIAL HEAl.TR , ('.VC tions in the Study of Cancer in Industry, Am. J. 41. Gloyne, S. R.: Pneumoconiosis: A Hint* Pub. Health 44:1159-1166 (Sept.) 1954. logical Survey of Xecropsy Material in 120j P, 25. Davies, D. F.: Current Status of Lung Lancet 1:810-814 (April 14) 1951. Cancer Research: Some Pathogenetic Aspects, 42. Gloyne, S. R-: A Case of Oat-Cell t CA 6:169-174 (Sept.) 1956. cinoma of the Lung Occurring in AsiWm. 26. Desmeules, R.; Rousseau, L.; Giroux, M., Tubercle 18:100-101' ( Dec.) 1936. and Sirois, A.: Asbestosis and Pulmonary Cancer, 43. Glov ne, S. R., and Merew ether. E R. Semaine de. hop. Paris 2J:1820-1823 ( Aug. 7) Asbestos, Occupation anil Health, Supplement 1947. Encyclopedia on Occupation and Health, Genera, 27. Doll. R.: Bronchial Carcinoma: Incidence International Labor Office, 1938. and Aetiology (Milroy Lectures, abridged), Brit. 44. Goldblatt, M. W, and Goldblatt. J.: In M. J. 2:521-527 (Sept. 5): 585-590 (Sept. 12) dustrial Carcinogenesis and Toxicology, in In. 1953. dustrial Medicine and Hygiene, edited by E. R. A. 28. Doll, R.: Mortality from Lung Cancer Merewether. London, Lomton, Eutterworrh A Among Asbestos Workers, Brit. J. Indust. Med. Co., Ltd.. 1956, Vnl. 3. pp. 185-188. I2:8t-S6, 1955. 45. Haeiiszel. W. M., Epidemiological Te'is of 29. Donnelly, J.: Pulmonary Asbestosis, Am. J. Theories on Lung Cancer Etiology. Pub. Health Pub. Health 23:1275-1281 (Dec.) 1933. Rep. 71:163-172 (Feb.) 1956. * 30. Dom, H. F., and Cutler, S. J.: Morbidity 46. Hammond, E. C.: Lung Cancer and Cnw from Cancer in the United States, Pub. Health mon Inhalants, Cancer 7:1100-1108 (Xov.) 1954, Monograph Xo. 29, P. H. S. Publication Xo. 418, 47. Hammond, E. C.: Etiology ot Broneniogemc. U. S. Public Health Service, 1955, 121 pp. Carcinoma, CA 6:156-168 (Sept.) 1956. 31. Dom, H. F.: Cancer Morbidity Surveys: A 48. Holleb, H. B, and Angrist, A.: Bronchia Tool for Testing Theories of Cancer Etiology, genic Carcinoma ir> Association with Pulmonary- Am. J. Pub. Health 45:615-621 (May) 1955. Asbestosis: Report of 2 Cases, Am. J. Path. 18: 32. Egbert. D. S., and Geiger, A. J.: Pulmonary 123-135 (Jan.) 1942. Asbestosis and Carcinoma: Report of a Case with 49. Hi.mburger, F.: The Co-Incidence ot Necropsy Findings, Am. Rev. Tuberc. 34:143-150 Primary Carcinoma of Lungs and Pulmonary (July) 1936. Asbesto-is: Analysis of Literature and Report 33. Ellman, P.: Pulmonary Asbestosis: Its of 2 Ca.ies. Am. J. Path. 19:797-807 (Sept.) I MX Clinical, Radiological, and Pathological Features 50. Horn. D.: Is Lung Cancer on the Increase?. and Associated Risk of Tuberculosis Infection, ^Evaluation of Present Day Evidence: Cancer of . J. Indust. Hyg. 15:165-183 (July) 1933. the Lung. Proceedings of the Scientific Sectioiv- 34. Ellman, P.: Pulmonary Asbestosis, Proc. Annual Meeting, American Cancer Society, Inc, Roy. Soc. Med. 34:557 (July) 1941. Xov. 3-4, 1953. 35. Fed, A.: Pneumoconiosis in Asbestos 51. Hornig, F.: Clinical Considerations on the Workers, Presse med. 39:1872*1874 (Dec. 19) Question of Industrial Cancer of Asbestos Work 1931. ers, Ztschr. XrebsforsclL 47:281-287, 1938. 36. Fulton, W. B.; Dooley, A.; Matthews, J. L-, and Houtz, R. l_: Asbestosis: Part III. The Effects of Exposure to Dust Encountered ia Asbestos Fabricating Plants on the Health of a Group of Workers, Special Bulletin Xo. 42, Pennsylvania Department of Labor and Industry, Bureau of Indust. Standards, Sept. 20, 1935. 37. Gardner, L. U., and Cummings, D. E.: Studies on F.xpenmental Pneumoconiosis: Inhala tion of Asbestos Dust; Its Effect upon Primary Tuberculous Infection, J, Indust. Hyg 13:o5-Sl ( Feb ) ; 97 (March) 1931, 38. Gilliam, A. G. : Mortality Trends in Lung Cancer, Cancer 8:1130-1136 (Xov.-Dec.) l'*55 52 Hueper, W. C.: Cancer in Its Relation to Occupation and Environment, Bull. Am. Soc Control Cancer 25 63-69 (June) 1943. 53. Hueper, W. C.: Significance of l;viu?:r-.al Cancer in the Problem of Cancer, Ocoup 2.190-200 (Sept.) 1946. 54. Hueper. W'. C.: Environmental and Occupa IOM 14 tional Cancer. Public Health Service, Supp 2(9, L1. S. Public Health Service, 1949. 55. Hueper. W. C.: A Methodology- for Environ-, ot In Imental and Occupational Cancer Surveys, Puhiic Health Monograph No. 1, P, H. S. Publicans Xo. 12, U. S. Public Health Service, 1950 56. Hueper. W. C.: Environmental Lu.'.z Ho p- 39 Gilliam, A. G.: Mortality Attributed to Cancer. Induct. Mfit. 20:49-62 (Feb) 1951 Lung Cancer in the Large Cities of the United 57. Hueper, W. C.: Occupational and Environ-- States in 1943 and 1949, J. Xat. Cancer Inst. mental Pulmonary Cancers with Special Reference-- 15 1307-1312, 1955. to Pneumoconiosis, Proceedings. 7th. s uar.jC 40. Glome, S R Two Cases of Squamous Symposium on Pneuino oniosis. 1952. Carcinoma fit the Lung Occurring in .Watstosis, 58. Iluei>er, W. C.: A Que-l into the i uviron- Tubercle 17.5-10 (Oct) 1935.^;.- z : i f - 's* - ' . ;1 - invntal Causer-on CnuTTf i pt the Lung. Pu'-`- ,' ' ' J i (J. I'A NOT fflMF FRfifol P?fi FILES LiLSTM!* I. L'XG CANCER IN ASSmUgS.MINERS Health Monograph No. 36|79j9fc7& Publication No. 452, U. S. Public Hcaflpihrvice, 1955. 59. Hueper, W. C.: Environmental Causes of Cancer of the Lung other than Tobacco Smoke, Dis. Chest. 50:141-158 (Aug.) 1956, 60. Isselhacher, K. I.; Klaus, H,, and Hardy, H. L.: Asbestosis and Bronchogenic Carcinoma: Report of One Autopsied Case and Review of Available Literature, Am. f. Med. 15; "21 -732 (Nov.) 1953, 61. Kennaway, E, L., and Kennaway, X. M-: A Study of the Incidence of Cancer of the Lung and Larynx, J. Hyg. 36-236-267 (June) 1936. 62. Kennaway, E. JL, arid Kennawav, X. XL: Studies of Incidence of Cancer of ihe Lung and Larynx. Brit. J. Cancer 5:155-158 (June) 1951. 63. Klotz, M O,: Association of Silicosis and Carcinoma of the-Luflg, Am. J. Cancer 35:38-49 (Jan.) 1939. - - - 64. Lanza, A. S~r-McConnell. W. J, and Fehnel, J. \V.: The-Effects of the Inhalation of Asbestos Du<t on tbe Lungs of Asbestos Workers: Pre liminary- Study, Pub. Health Rep. 30:1-12 (Jan. 4) 1935. 65. Lanza. A. J., editor: Silicosis and Asbestosis, New York and- London. Oxford University Press, '938, 1ft Lew, E.'A.: Use of Life Insurance Comahy Records for Cancer Studies, A. M. A. Arch, ndust. Hyg. 5:198-203 (March) 1952. 67. Linzhach, Al J,, and Wedler, H. \V.: Occu pational Cancer among Asbestos Workers, Arch, path. Anat. 307^7-409, 1941. 68. Lynch,-.ICr XL^-and Smith, \V. A.: Pul monary Asbestosis "Carcinoma of Lung in Asbesto-Silicosis. Am. J. Cancer 24-56-64 (May) 1935. 69. Lynch. K. XL. and Smith, W. A.: Pul monary AihestO'is; A Report of Rrotichial Car cinoma and Epithelial Metaplasia, Am. J. Cancer 36.567-5*3 (Aug.) 1939. 70. Lynch. K. XI.. and Cannon, \V. XL: VbesAnalysis of 40 Necropsies! Cases, Dis. Chest 14.874-889 ( Nov.-Dee.) 1948. 71. McPheeters, S. B.: A Survey of a Croup ' Employees Exposed to Asbntxw Dusr, I. )j't. Hyg. 18-229-239: (April) 1936. 72. Mertwether, I-,. R, A,: Th.e Occurrence nt IV.hv.miary Fibrosis ,md Uther Pulmonary AlTec''.(pS (ii \*hes:p;s Woikery I Ir.duct Hvg 12: ifj8 (May); 229 ( lime) loji). 73. Mercutiher. F.. R X , and Price, C, W,: Rvj-ort 0,1 Elfecis Pit A'be-tos Du-t mi inc Lungs ..:.p| Dint Suppression in the Asbestos Industry, Lmi'lon. His Majesty's Stationery' (blue. 19.10. Merenether, E- R. A.. A .Memorandum p,n 'tosiy Tubercle 15:109; (Dec.) 1933; 15. ijan.j 1934. Prtllin--Trttan 75. Merew ether, E, R. A.: Annual Reports of (he Chief Inspector of Factories, London, His .Majesty's Stationery Office, 1947. 76. Merewether. E. R. A., editor: Industrial Medicine and Hygiene, London, Butterworth & Co., Ltd.. 156, Vol. 3. 77. Nordmann, XL. The Industrial Cancer of Workers in Asbestos, Ztschr. Krebsforch. 47 :288302, 1938. 78. Nordmann, XI, and Sorge, A,: Pulmonary Cancer Produced by Asbestos Dust in Experi mental Xmmnls, Ztschr. Krcbsforch. 51,168-182, 1941. 79. Phillips. A J.: Mortality from Cancer of the Lung in Canada (1931-1952), Canad. Xt. A. J. 71 242-244 (Sept.) 1954. 80. Saupc, E.: Further Contributions to the Roentgenological Diagnosis of Asbestosis, Arch, Gewerbepath. u. Gewcrbehyg. 9:391-106, 1939. SI. Smith, K. \V.: Pulmonary Disability in Asbestos Workers, A. XI. A. Arch. Indust. Health _ 12:198-203 (Aug.) 1955. 82, Smith, L. W.: Pneumoconiosis and Lung Cancer with Special Reference to Silicosis and Asbestosis, Coinpens. Xled, 2:3-10 (Nov.) 1949. .83. Smith, W. F,.: Survey of Some Current British and European Studies of Occupational Tumor Problems: Part III. Asbestos, A. XL A. Arch. Indust. Hyg. 5:242-263 (March) 1952. 84. Stoll, R.; Bass, R., and Amtrist, A.: Asbestosis Associated with Bronchogenic Car cinoma, A. M. A. Arch. Int. Xled. 88-831-334 ( Dec ) 1951. 85. Telcky, L.: Occupational Lung Cancer, Acta Union iuternat. coutre Cancer 3:253-273, 1938; also. Zentralbl. Gewcrbehyg. 27 33, 1940. s6. Vorwald, A. J : Durkan, T. XL, and Pratt, P. C.: Experimental Studies of Asbestosis, A. M A. Arch. Indust. Hyg. 3:1-43 i Ian.) 1951, CTs '-Aj ^ 8*. Wedler, H. W.: Asbestosis and Lung Jaiicer. Deutsche rued. Wchnschr. 69 575-576 \ug. o) 1043. 88. Wegelius. C ' Changes in rhe Lungs m 126 Lists .it \-bestr.sis Observed in Finlan'L Acla adinl, 28,139-152. 1947. .*1^ Ck_ o9 Wcrber. M. . Pulmonary Asbestp>~i> Asso.i.iied with C .ircinoiua, Zentralbl, Arlieit-med. u. \rbeits-ebutz -2 179-180 (Nov.) 1952. o r>- ' 0 W.vi.l, W B. ,md Glovne, S R : Pulmonary \-besinsrs Complie.ited bv Pulmonary Tuliercu- p.'is, I ..il rs'Cl 2.9-4-956 i Oct, 31) 19J1. . "1 W\i-r-. H, A'bcsto'is, Postgra.l Med. 25:, <1-638 (Dec) 1949. UJ o o ''2 Wynder, F,, L., and Graham. E. A. liinlo'cir baeturs in Bronchiogenic Carcinoma-- mil S|s-(i:il Refereme to Industrial Exposures;* scix.ri i'f Proved Cases, A, XL A. Arch, in lust. live. 4-221-235 (Sent.l 1951. I(- ,653 I ''I ;j ' a J J "t.'s LABORATORY Reprinted from the A. M. A, Archives of Industrial Health June 1958. Vol. 17. pp. 634-653 Copyright 1958, by American Medical Association -- ^N An Epidemiologi Lung Cancer itf _..~TDU\L HYGi ------ - Kt'\\ ia "'r % fih fwe PitoW*" U' 4400 FnTM ftve" DANIIL C. MAUN, M.D., nd Ever since the pronounced increase in the incidence of lung cancer among males became apparent, there have been attempts to associate it with one or another of the various elements in the environment of man. The approach used by some workers has been to suspect one or several sub stances and then set about in an intensive search for lung cancer among persons who have had any exposure to those materials. In this connection, Smith82 writes: "The tendency of authors reporting the coinci dental occurrence of primary lung cancer with silicosis or with any other theoretical etiologic conditions, has been to emphasize the percentage relationship in extremely small series of cases, with control cases which are not in any way comparable." It would seem inevitable that asbestos should come under scrutiny in this manner, because prolonged exposure to this material is known to cause a specific type of pneu moconiosis, and because persons who show this form of pneumoconiosis often come to autopsy and provide a ready source of material for study. It was in this way that reports of the simultaneous occurrence of lung cancer and asbestosis began to accu mulate after the report of a case by Lynch and Smith * in 1935. Within the next 10 years, about 15 additional cases were re ported. and in 1954 Merewether T* reviewed all deaths from asbestosis recorded in Eng land since March, 1924. Lung cancer oc curred in 16% of these cases. Gloyne,41 whose work is also frequently referred to as establishing a connection between asbes tosis and cancer oi the lung, reported in 1951 that cancer of the lung was present in 14.1% of asbestosis cases examined by him. In 1941, Xordmann and Sorge7fr claimed to have produced lung cancer in mice which they exposed to asbestos dust. Since 1931, additional cases of cancer of the lung coexisting with asbestosis have been reported, and, according to Huer>er r,i about 100 such cases had been reported up to 1955. As a result, an association between the two diseases appears to have been ac cepted by many authors, and several writers were using the term "asbestosis cancer" of the lung. Werber,** in 1952, stated cate gorically that in 7% to 17% of cases of asbestosis, after a latent period of about 1 y3 to 20 years, carcinoma becomes estab lished in the lung. On the other hand, not all authors ac cepted this alleged association without reservation. Saupe 80 in 1939 reported that he had discovered no cases of lung cancer among 620 cases of asbestosis which he had examined; and in 1942, Holleb and Angrist4* expressed the opinion that the number of cases of asbestosis with lung cancer was too small for statistical evalua tion. In 1947, Wcgelius ** reported 126 radiologically diagnosed cases of asbestosis among 476 workers in Finland, and found no cases of lung cancer in this group Goldblatt and Goldblatt in their section of Accepted for publication Jan. 20. 19S8. Merewether's latest book,44 state: L,ut a: This study was made possible through a grant no stage in all these impressive researches from the Quebec Asbestos Mining Association. Medical Director (Dr Braun) and Statistical Consultant (Mr. Truan), Industrial Hygiene was any clue obtained which might have offered anv support to the possibility that Foundation. NOTE: TH W*'"- Therc - 634 NOT COME FROM PPG FILE*_ _ _ _ _ ----- ---------------------------------------------------------- BB 0005S0fi* CU 3028S Lt XG CAXCLR IX AsliLSTCS MIXERS is iu> reliable criterion by which one cm auiieip.ite careinugenicity ami. a? is well known, relatively minnte change.' in the Structure of a chemical carcinogen are suffi cient to diminish or eliminate carcinogenic action. If asbestos is indeed to be regarded a- a carcinogen, the need is felt to demonstrate some property which can be regarded as something more than inertness." These authors advance the theory that, until some more experimental evidence of direct carcinogenesis by asbestos or a de composition proJuct of it can be obtained, asbestos might be considered as a "co-car cinogen" which only induces a further de velopment of a preneoplastic condition brought about by something independent of tlie asbestos, such as an endogenous factor. Thus the literature, while tending to sup port the thesis that asbestosis is in some way related to the development of lung cancer, is by no means unanimous. Alto gether, it is perhaps more confusing than enlightening. A careful review shows that the majority of the reports are clinical and not epidemiological. They lack many ele ments necessary for the application of epidemiological techniques to their content, and most of the authors do not make claim to having done so. What has happened is that succeeding authors have drawn conclu sions and generalized beyond the scope of the works which they quote. Nowhere, for example, have we found references to a population of asbestos workers, although several authors who have quoted the ob served incidence of lung cancer in autopsies of persons who also had asbestosis imply that this incidence applies to asbestos work ers, generally. We have likewise been unable to find any study which actually calculated the incidence of lung cancer among a population of persons who had asbestosis, and not just those who came to autopsy. With the exception of a pa]*er by Doll,2 none of those reviewed gave any data on exposure and dust concentrations, and even Doll's paper merely mentions "'chedulrri" area;, by which i- meant "thi*v area- where procc-'e- are carried ut; which were scheduled under tin A-U-to- Indu^try Kegulation- of ]p.M bemg dusty." There i.-. furtin.:; ,, ,;v. .. .. of definition of tern - a- u-n. ! tiv pub lished literature. F->r example, the tc-.m "a-djestosi'," a- u*ed. mav ref--- to 'bargeobservable only by miero-eop-- cxa-'ni;a'.,":i of the lung tissue, or it may me.-.:, a -aFologically delectable condition. Most of the published re;---tincluded women among du-i* c-i.-e- ir.r -ome of them do not give thi nur.. profiortion of women involve-] in the study. There i' als<i a kick of uniformity what type of expo-urc- mo-: stti-ke.- h.v e dealt with. Of 99 case- enumerated by Hueper '1 in 1955. only 10 apiwar ha-e originated in the United States, and 7 in Canada. Some of the earlier rqx>rt- ap parently included asbestos miners, but it can be assumed, since S2 of the 99 ca-es had originated in England, and since ikasbestos 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, fundi history of cancer, length of time in the industry, and age of the individual can. are abci notably absent in the majority of these reports. With thi' understanding of the limita tion' of the existing literature with resfiec: to epidemiological generalization, it may U 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 studie> and one which deserves the most serious considera tion is that reported by Doll2S in 1955 This study reviews causes of death among asbestos workers based on coroners' rec ords. ll also attempts to estimate the ri-k by studying records of nien who workej for at least 20 years in exposed situations Bram--lrutm iM.j ^ > , -ijOiVu. ;i<UW I BB 0005807~7 It  *i*^ _T-, * * ' ^ v4$S = CU 3 .-). ,U. .-? ,AkUU\'L\ Ul I.\ I >! STK1AL Ill.tlJi: Doll concluded that lung cancer was a spe lung cancer in other forms of pneumoconio cific industrial hazard of certain a-besto- sis wa- 6.79c. and in 169 ca-e- which workers ami that, after 20 year- of expo proved not to have any type of pneumo sure. the risk is 10 times as great as for coniosis it was 8.39c. Gloyne con-idered the general imputation. "the mortality of the asber-to- worker-" to This article is important for several rea be "disturbing." First of all. it is obviousons. in addition to the definite conclusion- that the ]>a|>er doe? not deal with the "mor at which it arrives. For example, it beginbv stating that ``in view of the infrequency of asbestosis. this large numl>er of case.161 cases of lung cancer) suggests--but does not prove--that lung cancer is an occupational hazard of asbestos workers." Neither this article nor any previous one tality of asbe-tos- workers." and secondlv. it must be borne in mind that all of Dr, Gloyne'> case- were submitted to him for study because the findings were unu-ual for uncomplicated pneumoconiosi-. It can reasonably be assumed that cases, including those of asbestosis. in which the finding- which we have examined presents any fig ures to prove that asbestosis is an infre quent occurrence. Estimates of the number of persons potentially exposed to asbestos dust in the United States alone vary from 10.000 to 35,000, and the incidence of as bestosis of any degree might be higher than Doll imagines. This study, like so many others, involves autopsy records. The number of persons involved in the statistical analysis is only 113, representing only 1,042.25 man-years of life. It is also true that in selecting men who had been employed for at least 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 be a hazard t in asbestos workers) has been produced by Merewether and by Gloyne." In 1951 Gloyne41 presented a review of 1205 autopsies on persons who had worked in various dusty occupations. This number included 132 asbestos workers, of whom 121 showed "pneumoconiosis"--pre sumably asbestosis. Primary cancer of the lung occurred 17 times in this group, an incidence rate of 14,19c for h*-*T cancer among asbestosis cases coming to autopsy. There were in his series 796 cases with sili cosis, and 6.99c of these also showed pri were not considered unusual were no; -cm to Dr. Gloyne for examination. As a mat ter of fact, in the same paragraph in which he expresses concern over the incidence rate in asbestosis. Dr. Gloyne himself points out that the rate lor lung cancer based on necropsies at the London Chc^t Hospital was 21.3rc while the figures of the Registrar-General showed only 2.49c. He thus recognized that autopsies on a cer tain selected group of cases were no; rep resentative of the general population. It would seem, then, that notwithstanding the value of Dr. Glovne's work, its importance as an index of the prevalence of lung can cer in asbestotics has been misinterpreted by some who have quoted him. All that it really shows is the fact that in a group of 121 cases, selected for special studv pri marily because they seemed abnormal bv preliminary examination. 17. or 14.ID, had lung cancer. Merewether in 1947. in the rci>eirt of the Chief Inspector of Factorie-. reviewed all cases reported between 1924 and 394o in which asbestosis was the cause of death or a coexisting condition. This work was later extended to include all such cases re ported up to December, 1954. by which time there were 344 deaths, including 205 maleand 139 females. Among them were 55 cases (16*^) of cancer of the lung. 41 in males and 14 in females. It is quite possible that a large number of asbestotic- who did mary cancer of the lung. The incidence of not die of their asbestosis. or in whose 636 NOTE: THIS DOCUMENT EUDk w . NOT COME FROlVI PPG FILES'^ .nr | BB 0005308 death certificate it wa? not mentioned. may prior to that date- and enum*-rati-d * o have been missed, Thv import of thiis enhanced by the simulianeou? -tatement that the incidence ut* lung cancer in autopsie? of the genera! jK>]*ulnti"n i- only l*r. The danger oi attempting in compare a rate found in 344 cases with the rate for the general imputation without resj-ect to of 99. Eleven of the-e were th...........-- cu.-?ed hv 1 >oll *' and may havv bert: ? covered bv other author-. Eiglr weri -- covered by Kennaway and Kennaway ' * :r. an analy.'is of death certificate-, and. Mercw ether"? study wa- incomplete case? should have been included u. h * age, occupation, and many other variables, such as smoking habits, is obvious. Lynch.*0 who with Smith ** had reported the first case in 1935. reported 4 cases of carcinoma of the lung in a series of 49 fmrt. Of the remaining S" it i- qu"- siblc that the 31 contributed by Mcrew*. and the 17 by LI*-yin- contain ?ome dup tion with each other or with th---e of English author- autopsies on workers in an a?l>e?to? manu facturing plant who were shown to have "demonstrable dejiosits of asbestos in the Principles of the Epidemiological Method lungs." This, of course, is not necessarily Dorn 3" ha? pointed out that much o; w . identical with the disease ashestosis. Lynch, is now thought to be pertinem concert/ t: himself, points out that, although this is an the comparative frequency of lung can- r incidence of 82r`c. "both figure4 are too in different population group- ha? beet; - small for very serious statistical types oi veloped from the analysi? of clinical : - calculation." Nevertheless, later writers terial, particularly surgical and au:*-p-- have used this paper to strengthen the case records, supplemented to some extent- 1 for an association of carcinoma of the lung the reported impression? of various du with asbestosis. It is also of interest that rian? based upon their personal ob?er\ : Klotz83 found only the same number of lions. More recently, however, attentt"' cases of lung cancer in a series nearly 10 has turned to the systematic investig. times as targe, i. e.. 4 in 478 cases of tion of this problem by the same meth"-- asbestosis. that have proved so successful previou-ly : Behrens, as cited by Merewether.78 esti the study of communicable disea?c.-, that mated that, of 309 cases of asbestosis in the to say. by epidemiological methods. literature, 44 showed associated cancer of In order to apply this method of ime?' the hing--giving an incidence of I4.2fr. gation to the problem under discus-ion. w. This is an illustration of generalizing an were of the opinion that a study should E incidence obtained in a group of cases planned so as to provide ill a well-defim which were undoubtedly reported only be imputation group: l2l avadable data for T cause some of them showed lung cancer, to member? of this population, including tin possibly hundreds of asbestotics whose healthy as well as the ill: i3 a snmpk cases were never reported. The same ap which is truly representative oi the jmpu'.t plies to the conclusion of Teleky.8'1 who tion: (4f reliable and \a)id observatii-i-- appears to have reviewed reports of 39 relating to the problem of the study autopsies on persons with asbestosis among which 6 cases of lung cancer occurred. In formation from sources such as these does not justify generalizations with regard to mortality rates. A serious defect, common to most of thi studies which ha\e been reported, i- th./ little or no information concerning thi healthy people in the grot., ?eem? to haw been available to the author. In order t. Perhaps no one has written so exten draw a generalization regarding all asU-st-- sively on the subject as has Hueper.3310 workers, it is necessary for a study to n. In 1955 he reviewed the casess* r Braun--Truan r.eltudeul\ivqingphtierp-o\ns'.ra.sirwveTll asntihne de.v* I\ 7 r n < i --r\ ;vj ^BB 0005809 A. AT. A. ARCHIVES OF IXPLSTRIAI III.AITH Limiting the investigation to case? coming to autopsy, as has been frequently done in earlier studies, still further restricts its use in generalization. The problem with which we are concerned is whether asbestos miners experience more lung cancer than does the general population. The answer necessitates the collection of reliable infor mation on asbestos miners as a group, as well as on the general population. It seems advisable to discuss the differ ences between the epidemiological approach and that used in the studies which have been reported to date. A very important consideration is the fact that lung cancer, in spite of its increasing numbers, is still a disease of low incidence: that is, in a given population not many persons will contract this particular disease. This fact requires that large samples or groups must be stud ied to provide meaningful results. Recognizing the difficulty of obtaining such large samples, most earlier writers deviated from the epidemiological method and sought to circumvent the requirement of observing well persons by (1) compar ing the relative frequency of cancer in vari ous sites: (2) comparing the relative frequency of cancer in a group of hospital ized patients: (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 body sites, may result in finding a higher f>ercentage (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.30 The mortality rate from a particular cause is the true measure of comparison. . is apparent that selected groups such as hospitalized patients or autopsy cases may not be in any way representative of a larger group, and that in dealing with such samples, the observer may easily find more cases of a given disease than would be found in another group of the same size, but representative of the general jiopulatiun. It is true that investigation of ca'-e- from such a sample can furnish information valuable for research, but the u-c of thiinformation in drawing generalization- i<necessarily restricted. It is the obligation of both the investigator and of tho-e who read his report to make proper comparisons and to draw only those conclusions which are valid and justified. A good statistical study of cases of cancer of the lung occur ring in a group of autopsies can lead to a proper inference concerning the frequency of lung cancer among cases coming to autopsy, but only to such cases. For in formation from such a study to be pro jected to some larger group, it is necessary that the autopsies represent a good sample of that larger group. To assume that such is the case in any particular series is dan gerous and likely to be false. There is some danger that the figure.reported by some authors may be miscon strued as applying to asbestos workers or even asbestos miners, when, in fact, the authors in question do not make this gen eralization. nor can the generalization be made for the reasons stated. Close study of the reports reveals that the percentagecited relate only to the group oi autopsies covered by the particular investigation. The present study, in contrast to the earlier works, has been planned to utilize the epidemiological method. A well-defined group of asbestos miners has been estab lished in such a way that it constitute- a good sample of the whole population of asbestos miner- in Quebec. Data for all member? of this group ha\e been collected and analyzed. Those concerning lung can cer have received most careful considera tion. Details of the methods employed w ill be set forth later, but the type of approach is considered to permit of fair com[iari>ons and valid generalizations Collection and Analysii;b| ijata'l ,0 A preliminary survey of potential sources ^ 638 | BB 0005810__ NOT COME FRGiVi ppQ fn pr ** ysV**^ -- ^. bv*^c-- - ' sgUr:-'- . :^7i^r. -- M. . , sSev l.r.\C t'ASCER IS A^Rt.S T<>\ MISER.s CU discussions with the physicians in charge of the asbestos companies' programs and with clinicians, pathologists, reproentatiwof City and Provincial health departments and of the Canadian Cancer Society, and other interested per-ons It was found that morbidity data, although somewhat limited, were available from such source- n the hospitals in Montreal and (Quebec City, and the 13 cancer detection centers in the Prov ince. However, because of the high mor tality in lung cancer, it seemed advisable to depend upon data relating to deaths. These we found to be obtainable at the vital statistics department of the Ministry of'Health in Quebec City. From the pre liminary survey, it was apparent that exten sive and detailed information could be gathered with respect to both the persons employed in the asbestos mining industry and the mortality figures for the general population. Following this exploratory survey, the initial effort was directed to the collection of data relating to all workers who had been processed through the clinic at Thetford Mines since its inception in 1947. and similar information regarding all workers at Asbestos, Que. Data from the clinical records included the age. family and per sonal medical histories, smoking habits, number of years of exposure, an estimate of weighted exposure, and the course of the individual's health status or the cause of his death. From this information it was possible to formulate a "cohort" which could be well defined, should be representative of the whole group, and could be followed for a definite period of time. All of the available experience indicates that the development of asbestosis in less than five years of ex posure must be somewhat rare. Accordingly, the cohort was defined as including every miner who had a total exposure of five or more years, and who was on the employment rolls in 1950. Office and other nonexposed personnel, regardless of length of employment, were not included. This cohort wa- then followed by mean- nf the annual physical examination recordthrough a six-year interval. 15" through 1955. All data regarding this gr*-;:, were then tabulated in order to detent the characteristics of the cohort. For thi--.- who survived the entire jierifxl. retVren-e wa? made to the physical examination -esults and x-ray findings at the end of th<. period. Tho-e who had died were tabulate -epa* rately, and the cause of dead was corroborated by examination of thi death certificates. A further search wa- made concerning those in the original coho- who remained unaccounted for when the being and the known dead had been tabulated. They represent men who had left employ ment through retirement or resignation. Eventually, all but a small numt>er 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 Ii~: 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 cau>e of death, but in which it was not sj>ecified a.- 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 studv. The statistics for the Province oi Quebec relate to population, total deaths from all causes, total deaths from cancer of all types, and death; . com lung cancer. The>e were collected and tabulated by counties and hy sex for the vears 1950 to 1955. inclusive. Braun--Truan 6.W iD :j.w.j1.iv;.;;- ,; riL-Ci bb ooosbTTT .AKlltm.S Of IXDCsTKJAl. HfAt.TH From them, death rates for the genera! population of Quebec and of individual counties were calculated for specific years and analyzed by cause. Practically all employees of one company are covered by a group policy of life insur ance which, fortunately, nearly all of them continue to carry when they retire. A very few are not covered by this policy, and those who leave the industry for one reason or another except retirement usually are no longer covered, but this is likewise a small number. As an additional check upon the information obtained from the clinical records on this group, the records of the life insurance company were examined for all death claims paid under the policy, and particular notice was taken of the claims in which the proof of death was based on cancer of the lung. Deaths from lung cancer among asbestos miners were thus determined from the clinical records in the medical service of the industry and checked by means of the death certificates and insurance company records. 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 cases in which lung cancer is strongly suspected but not proved as the cause of death were considered separately. Mortality rates have been calculated using both the "proved'' and the total of "proved" and "suspected" cases during the years un der observation. Comparisons were then made between the death rates from the same cause among specific segments of unexposed persons. All lung cancer deaths, both suspected and proved, were carefully ana lyzed to determine possible relationship or correlations between the development of lung cancer and any factor known from the clinical records, such as family history of cancer, personal history of heavy smoking, coexistence of asbestosis, or exposure to asbestos. In addition to this analysis of deaths oc curring in the cohort and during the years under observation, every known death front cancer of the lung, as well as every case diagnosed but still living, has been tabulated and analyzed. They will be discussed eeparately from those included in the population and time-interval under study. A comparison of lung cancer mortality in the asbestos-producing counties has been made with that in counties which are far removed from the asbestos mines and in which, presumably, no asbestos miners live. Finally, in order to broaden the compari son of death rates in different population groups, the rates have been collected for Canada generally, and for the United States, according to the most recent published and unpublished material. Results and Interpretation The cohort which was constructed accord ing to the criteria described in the preceding section has been considered individually and compared with the general population. Description of the cohort will be presented here as a preface tothe results of the study : Original Cohort Lo,*t Peraonft Deducted Final Cohort Living in 195? {norLinp anti renretl) Dead bv 1?5 Caneer ot lung Questionable ranter of lunjr Other cau*e* \`nknnn rauve* NofMmoker* Vnknot* n .091 133 5.95* 5.771 Q J 160 e 4 673 Tables 1. 2. 3. and 4 present age. number of years of employment, weighted average exposure, and minking habits of the cohort A compari>on of the exposure to asbestos dust is presented in Table 3. All tneml>ers of the cohort were placed in one of three categories, representing increasing degrees of e\|>osure based on a weighted average of the years spent at various levels of dustiness. The degree of dustiness for each job category was determined after consulta tion with persons familiar with the environ ment and conditions in the various work 640 ---------------------------------- MOT-' TVr . ' ' '' ` ~^ / I BB 0005812 | J sL/lv-. -J . ' tiXxh I T j , N0T GOMEfRefvhPPfrfltES- /.(AT, LAWI.k J\ .1 'Ll Ml SLR' cu (_v Table Air 1 --Xumber and Percentage by .Ige .. - - - Number Distribution - ---------J'er ( mt *J-H. ... ..... .......... U-M........................ 66+.................. .. . .. t'nknovru.............. .................. 3.60: \M' M* 3 . lv If ........ Avtr^e< Apt............ ;.&> ic* 4, * Lfik tfar. ft.s*rt. Table 2--Xumber and ]Jcrcentugc Length */ Lmpt. ym, t. ... -- - --------- - length of Emj.lii\fnu.; Nurr.S 4-V tft-N. . . ................ .................................. Y-W............... ........................... . 3t 'A** __ ., 4ti-4'_*. ......................................... y*-............................................. 1,7'.2..i> v:- Total* . .. .. .... Averav of n: ..... * 4'.' ; 'button by !'? Cm Y> 40 ic to 3 1 100 area?. For itu purjKJses of calculation, tinassumption has been made that the relationship between these categories is linear, and that Category 11 is twice as dusty, and Category III three time' as dusty as Category I. ually smoking more than fi\e ctg -cites per day. Persons who smoke pi|'e- or cigars exclusixely were not cons idered oe smoker' tor the purpo.e of th is stud. Table 5 [iresents the vear-b- ear experience of the cohort and in ': ,'.es the Table 3.--Xumber and Percentage Distributiem by Exposure Category Table 4.--Summer and Percentage Distribution by Smoking Habits Eipoiur* Ci*(ory 1................................ II .............................. Ill................................ Unknown.............. Touls............. A.n?r Exposure.... Less than 0.3% Number Per Cent Smokier Hibns Number i.rCut 2.031 2.1 it' 1.212 34 Smoker?................................................ 4.#73 3 Nomcioker?............................................ l.;*C 30 Unknown................................................. 20 : 21 * ------- -- Total?.......................... i.toi 100 s2.ois .ioo0--------------------------------------------------------- _____________________ * Less than 0.3%. The fourth variable, smoking habits, was similarly tabulated and is shown in Table 4. This was included because the informa tion was available and because smoking was regarded as one of the variables which, besides the environment, could conceivably influence the development of lung cancer. As used in this presentation, the term smoker refers to a cigarette smoker, habit- number of deaths each year from specified causes. In general, a case was cs-r.dJered to be "proved" as one of primary cancer of the lung when the records showed that the diagnosis had been supported i*\ an autopsy or surgical resection of the lung with microscopic examination of tin- remot ed tissue. In one case so considered, however, diagnosis was confirmed by bron- Table 5.-- Year-by-Year Experience of Cohort and Death Rates per JtX'tX'i Man- Years of Risk Ciuk of Death Y*kr No. Aliv* At B*ixuitac Of VftiiT ProvM Prlmurv Cft. of Vane Susp*cit<t Primary C*. of Lunc Oth*r Ciuyi Unknown Mdn*> t in of K:>W 1940............................... . 19&1......................... 1942.......................... 1943............................ 1944........................ 1966............................ Tout?......... 6.9 . 1 2 0 2 1 3 9 **Ftov4 " r*tt ptr 1C 1,000 mAn-yetn of risk ii.ru 12 'Toitl" r*u per 100,000 xnin*>t&rsof mk> 34.271.3 Braun--Truan 2 0 0 1 0 0 3 3U 12 17 37 U 33 36 109 1 3 1 i.937 0 4.9T.1 ' 0 SAr* ' 4 i.rpf 0 4.791* l 6 3? ::i ' Hu I 4 r ^s r :. JT DiD*[' i i r ja * -- ' M 'M i Ml NOT COME FROM PPG FILES | BB 0005813 3' \ * . ^-Ciic\j 03 .4 M .-1 AKl 111l `/..s Ol ISI.n.'iTRI ii. in.. Tabu. 6 --"Pmed" CaJt'i of Primary Ca>u-,r of ll c Lung CJ* No. 2 3 i 9 A f* t*. 66 6to5 4> hi V. 3T fia Smoker Yv? Yf* Yt` Yt* Yr* Yes Ye* Yi< 2li vr, in f`jt. II 34 vf, iti . J 3. vr, ir. f :*i, | 32 vr, in c .11 1 22 \r. in Cat II '&'& \ r. vn ill vr* wt ( a;. 11 U* vt. in ( ut, 1 vr. in C_ii. Ill t>iv! 1^ 12 M 5- 3 V. :-2*> -.M 4* [** *-< 11-22 Vt !r M o* -V* Autoji**> Yes Yf* No Vr* YtYvY> Yv* Bfiiiil. AsN Y ,\ N N Y V 'V N 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 ca>e; 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" lias been used to mean the number of men at risk for the year under observation. A person who lived throughout the year was counted as a full man-year of risk, but one who died during the year was counted as one-halt a man-year. Deaths occurring in the cohort, and in which lung cancer is considered to have been proved as a cause, are shown in Table 6. In Table 7 are shown three deaths which have been considered as "suspected" lung cancer cases. An indication of the importance of these "suspected" cases in interpreting the results of the calculations is desirable before fur ther discussion of the mortality rates which are derived in later tables. For example, it happens that the rate found for the proved cases is dose 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 dose to the 95 fr level of significance. However, having found iu;t 12 case;, we arc not above this le\d. and therefore the hypothesis that adiest*'; minerdo not ha\e a higher mortality from lung cancer than does the general j>opulaiioii can not be rejected. Nevertheless, the occur rence of 12 case- in this sample would increase the rate to a point which approaches the significant level. Because oi the tre mendous importance of the questionable cases in this respect, some detail regarding them will be given here. In one of these cases, the suspicion of cancer of the lung is based upon the x-ray interpretation, and. although no autopsy wa~ performed, the death certificate indicatethat death wa< due to lung cancer. It iwell known that the x-ray appearance of fibrosis, especially it a localized density ur a superimposed tuberculous lesion is pre-ent. can simulate that of a tumor, and by itself, does not justify the inclusion of tincase as one of "proved" cancer of the lung. A second case was certified as having died bv reason of hydrothorax, possib'.y due to lung cancer, but again there wa- :u> surgerv and no postmortem examinat "ii In the third case, although it was subjected to autopsy, two pathologists disagreed a< to whether lung cancer was present. The death was certified as having been due to chrome myocarditis with nephritis and pulmonary congestion, and possibly cancer of the lung. On the basis of these facts, it seems unwar ranted to include these three cases among Tabu 7.--"Sutferlfd" Primary Cancrr of tht Lang Cm Nq, l 2 t 642 A I* \% 46 66 Smoker Ye* Ye* Ye* Erpojur* S3 vr. tn CM. lit 33 tt- In CM. lit 43 yr. In CM. 11 nrc. Tjjjo Ui L. 1 ! > 11_> Died Autopsy A*b**t9i 10-25-60 T- -63 0-30-66 No Ye* No So Yf* No --------- - * - :.;SNTDft'. t K) 17, Junf. NOT COME FROM PPG F1L < ro555 itSSSff's&i&r--. -A* :~ "&-V .T cu 3/*.';: i.ixc l.i.u i.r ix .-/v/</.^ros mixi.r> "proved" instances oi lung cancer. On the other hand, they cannot, in fairness, be dis regarded completely. It is for this reason that mortality rates have been calculated both wav.-. Table 8 gives the rates by age groups. The rates by length of employment arcshown m Table 9. During the first 40 years of employment, the rate rises, an observa tion which seems plausible since the men were growing older. However, after 40 years of ex{>osure there are no "proved" cases retried for a total of 240 men dur ing the six years, or about 1440 man-years of exposure. When the "suspected" cases are added, one case does show up in this Table 8--Lung Cancer Death* by Age Grout's Tahll *>--Luny Cancer Lteatk' t". of Employment Number or Person* Numb Emplnyttu t.i 5-9 I4M9. W-."40-1*. TotJs....... Ni.. ot Person* Krvf. ZJy- W MM IV 5*. .W.s Annual Luny Canter Death Rate* per Mutt ^ ear* oi x(o*ure Lenrth t.f Employment $-9........... 10-1V................ 20-29................. 30-39................. 40-49........ ........ 50+................... Over-fti noth Number of Persons end Number of Lung Cancer Death* Age Group No. of Persona No- of Death* Pro red Total 3405--4M4................................................. $6-64.................... Unknown......... .. Totals............. A.IU6 13 Annual Lung Cancer Death Rate*- per 100,000 Man-Years of Exposure Age group Prove*] Total 30-44..................... 4$-54..................... $5-64..................... Unknown,.__ ... Over-on. dicates that the members of thv cohort did not die from lung cancer at a v-nmger age than the general population. The rates by weighted exj-osu-t are shown in Table 10. and it will U noted that they present strong evidence against asbestos being a carcinogenic agent, tor. if exposure to asbestos is in any way con nected to lung cancer, we would exj-eci that the longer and heavier the exf^-are. the higher the rate that would be found The only possible error in this interpretation could occur if the weighted exposure- were inversely related to years of employment. period. Thi> would produce a rate of 69 Table 10--Lung Cancer Deaths by Lx? sor, Category per 100.000, again demonstrating the im portance of these questionable, but un proved. cases to the final conclusion, because, if there were no cases in this number of men with long exposure, and if asbestos is a carcinogenic agent, it must be Number of Person* and Number of Lunn Cancer rath* EtpMurr Caie;or> Vo of Vrrjon? Nt of Pr *` pn>\M 1........................ 11..................... IU ................... Unknowo.* ....... 2,1.^* 5 concluded that these 240 men have demon Totl....... 5.V5> strated considerable resistance. This is a bio logical phenomenon which has been observ ed Annual l.unc Cancer Death Rate* rr Man Year* ot Exposure previously and is consistent with the theory RipftSur* of an intrinsic or endogenous factor in can Category rr-H........... FroT*a | u 11; j J cer. The only other explanation would be i........................................... it......................................... j. that the susceptible members of this age Ill ......................................... Unknown................................ 3* group had died earlier of lung cancer. Table OTr*U.i.................... .<4 NOTE: THIS18, which appears .later in this sect ion. in-_ --tttttv Braun--Truatt NOT COME FROM PPG FILES nr BB~0005815 NOTE: Tfits DOCUMENT DID *T' A lAl V.r*or Table 11.--.Vumfrrr of Persons in I ariuus Weighted Exposure Category* by Length of Employment length of Employment WeigChetetderoEnxprsosure ------------------------------- Un- I n ttt known 5-9 lu-19 20-29 3C-39 40-49 30^ 707 399 400 663 SKI 6M 314 363 243 247 21* 137 76 67 41 24 21 10 0 1 2 l 1 0 AveTngoeutysears 2,031 o( exposure i;ji 2,150 17.1 1.772 16.6 3 29.0 Total 1.795 2.396 922 603 163 33 5.936 174 in which case the heaviest weighted exlosure (Category III) would show the shortest length of employment. Table 11. which lists the number of persons in various exposure categories by length of employ ment indicates that this error has not oc curred. In fact, the average number of years of employment for each exposure category is almost identical. Table 12, which develops the rates for smokers and nonsmokers, is most striking. It shows that not a single case of lung cancer developed among the 1265 nonsmokers and that all cases of lung cancer, both "proved" and "suspected," occurred in smokers. Table 12 was so striking that it was felt that further verification was necessary. It was possible that some abnormal distribu tion may have occurred, e. g., the non- Tajle 13.--Sumber and Percentage Distribution of Smokers and Nonsmokers by Age Groups A(a Ornup 2TV+4.......................... 44-44.......................... 33-44.......................... 63+.......................... Untax>*Q*......... Totals.... . Aetna, m............. Number Smoker NonffDokcr 3.-200 896 411 164 .2 4.673 30.3 669 224 302 150 .0 1,263 4-2 Unknown 12 4 2 1 1 -- 20 40.7 Tablk 12.--Lung Cancer Death i-*r Smokers and Sonsmx>kcrs Number of Pervm** and Number of I.one ('am.fr 1***1 * by Smoking Habit-- No of l>Kltl4 Persons W**\M Told] Smokers................... Nonsmokfr? .*.*. . Unknown............... 4.673 1.263 30 9 h n 1.* i> i. Totals........ 3.936 9 13 Annual Lung Cancer Death Rate*' t*r iOu.^kj Mat* War* of Exposure by Smoking Habi'> No. o? I>eatb I'tovel Tnt.v Smokers....................................................... Nonsmokers,....*................................ Unknown........................................ 32 f> " -i " " Over-all........................................ 2^ :u 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 sho" s that as far as length of employment is con- TaDLE 14--Xumber and Percentage Distribut; of Smokers and Xonsmokcrs h\ Length of Employment Leneth of Employment 5-9.............................. tO-19........... ........... 20-29.............................. 30-39.............................. 40-49............................. so+-.............................. Totals............ Avenre length of employment*......... Number Smoker* Nonsm vker* 1.406 1,967 433 no 0.1 --4,673 3'7 4> 19 1 r+y . f. -- 1.2 A' 17,0 19.3 I'nktir-w m 10 4 4 It 0 -- yi l->0 Perttntaft Distribution t-tt Oroup 6mo Konmokcr 30-44.............................. *151--6M*.................................................. 6W- ......... .................. . Unknown.................... U! 1I9S.2 3-1 Ml 1176..70 116 0.0 Totals............ 100% 100% Unknown 60.0 3100..00 SO SO 100% * Im than QOS%. 644 Pm*nnr DiiTlbuiinn Lenrth of Employment Smoker Non*mok*r 3-9.......................... 10-19........................ 20-79............... ........... 30-39............... .......... 40-49**....................... 50+............................ Totals...... 30.1 42,1 134 93 2.4 0.7 100% 29 % 33: us r 13 1 39 18 100% Vnknow n <<l n 20 0 10 0 20 0 00 00 100 *"< Vnl IT. JUW.JW IJIB-QQ 058*16 U XG CAXCER IX ASBESTOS MIXERS Table IS.--Xumber and Percentage Distribution of Smokers and Xonsm-kerr by Exposure Category Exposure Cutf^'orj t... . u............................ in.............................. L'Okiwnf _____ Touli............. AT*ra eipojur. celtgory.. ........ Number Smokers Nonsmokers 1.663 \,*Vl i..> 4 -- i, 4.673 474 462 33-, l --i- nr 1.266 3.0 1.8 Vuknown 4 7 V 0 20 2.3 Eipnsur* Ciliary Perctmaje Distribution Smokers Noninjokers Unknown l..................................... It..................................... Ul..................................... Unkoovn.............. 33.3 36.2 30.6 0,1 3T.4 36.7 20.7 0.1 30.0 3i.l> 46.0 0.0 Total*............. 100% 100% 100% cemed. the smokers had worked about 2.3 years less on the average than the nonsmokers. With longer exposure and greater age, one would expect the nonsmoking group to show a higher rate it lung cancer were due to asbestos. Table 15 shows that the average exposure category was almost the same tor the two groups. Therefore, this variable seems to be of no importance in accounting for this difference. The result of this additional analysis is that none of these factors appears to lessen the effect of Table 12. Comporison of the Cohort Experience with Oust of the Province of Quebec, Do minion of Canada, and the United States.-- In order to make a comparison of the experience among asbestos miners with that of the general population of the Province of Quebec, statistics were gathered, as stated earlier, in the office of the Division of tu note:This document did NOT COME FROM PPG FILES Demography in the Provincial Mini-'rv of Health. The data on total death;, deaths from all forms of cancer, and death- from cancer of the lung were obtained bv sex and by county for the years 195" tlr^ugh 1955. In addition, all death cent, ates which Ejiecified primary cancer of tlv lung, and all those which indicated lung cancer but did not specify the origin, were ixamined for the years 1952 through 1955. Table 16 gives a tabulation of the number of deaths from lung cancer in the I To*, nice and in the cohort for the years 195" thr* .tgh 1955, and shows the annual rate- j*er l"".1 ".>0 in these segments. It will be noted iron 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 indudi-d in the calculation, the rate for the cohort ri`es to 33.8 per 100,000, which is about 50r higher than the rate tor the Province. This, it will be recalled from the previous dis cussion of the effect of the "suspected" cases on the results, approaches but d >es 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 un proved recognition and reporting of lung cancer during the interval. For this rea-on. the years 1954 and 1955 were thought to be more nearly representative of actual condi tions. Even so, it is quite likely that the general population is not studied for lung cancer with the same diligence with which Table 16.--Comparison of Cohort with Province of Quebec Lunf Cancer Deaths Annual * Rjsr# prr Persons 1960 1961 1962 1963 1964 1936 Totil lOC'.CHV PromTM 1.108.000 19ft 220 243 303 303 337 1,624 Cobon Total Proved Province 6,033 t 3 J 0 3 1 3 12 1 20 2 1 >0 1,192.000 m 2 If 244 300 302 344 1.612 (txrludi&f aabeatos vtjrkera) 27.6 33 * 22 j la the Province flg-crvv U hu been usaoied *U male lunf anar death* er* tor men ot 204- years. * Approximate midpoiat of the enumtrmtad population lor 1961, end ibe esttcoaiad population tor 1964 (Rapport, Dir. iDOCrephW). {Number alive la cohort at btftnnlnf of 1032. Bratm--TrMon la TV- 64r Aft Group 20-44 4.v,M 55-04 Total* AM AHi-llilT-S Of ISDCSTRIAL Ilf-U.Ti Table 17 --Lung Cancer Deat%* fcu-nkf f'rensnce of Quebec." ...... "M ' H C. ? 'J~f" Number ,,of Deaths 7*?n1 't-r-4- i =dfc= * * L# 19M Jim" a iUfvt14- :p im Total Certlfi*d specified Primary Toial Certified Srecfrtfd It if: F.ytlTTVJtfd J'optiLiK'i; Total proved ToUiJ Pnne-i Total Proved Total 1'r* 777 (iOO 137 .tM1 121.000 1,237.000 r n 11 ft? v> AS feioo 3* 69 m 33 295 130 191 9 IT 7i N* 32 117 2V 14* 9 17 3A 5*. 57 IKM Mb ft 342 liS 337 39: i-t Afc Group 20-44........................................................ 44-M........................................... -......... . 44-64........................................................ 664-..................... Orar-all................................................... Death Rate per 100.000 1244 Total CmiflMl Speclfit-d Primary Toni proved Total Proyed 2.2 23.2 73.0 21.7 1* 17.4 27.: 27.2 1.4 213 40 4 26,2 1.1 14.4 22,4 24.0 23.* 2.7 14.4 *0 1244 Tout CerttOo'l ;pacified ITitCiry Total Proved Total Pn-vxi 2.? 22,7 S4.4 122.3 1.2 17.3 41-0 44.0 2.2 27.7 S4.7 122.3 12 l: 41,f 44.*. 27.6 12.4 27.2 12 3 * Data (rom death rortlflcatvj. t Estimate for population obtaincl by ipplyin; 1241 peroentajel (or t(t croups (or males to the total population tor 1244. as ttrrr. Id Rapport, Dir. de la Demo(raphit. this disease is looked for in the miners, and it seems probable that the mortality rates for the Province may be low. This would appear to be substantiated by the fact that the reporting of cases in the cohort showed no such increase over the same period. Table 17 was compiled to show the an nual age-specific lung cancer rate of cases in which the death certificate merely read `"cancer of the lung," as distinguished from those in which the diagnosis was confirmed bv autopsy, surgery, or biopsy. The term "specified primary" refers to those cases in these two categories in which the tumor was specified as having originated in the lung. It will be noted that, of the total cases reported in 1955, a much higher percentage than in 1954 were specified as primary. The table also shows that a higher percentage of the total cases certified in 1955 were proved, again indicating increasing interest in this disease. A comparison has been made between the age-specific rates shown in Table 17, and those for the cohort, shown in Table 8. An average of the 1954 and 1955 rates for the Province has been used, since the 1955 figure was higher and may have been ex ceptional. This comparison, summarized in Table IS, shows that the observed number of deaths in our sample is not significantly greater than the expected number of death?, based on the average of the 1954 and 1955 figures for the Province. It is true that, in the case of the age group of 65 and over the five deaths provide a figure which ialmost significant at the 95fc level. How ever. it should be noted that thi> imiuhr includes one of the suspected but unproved cases previously referred to. Furthermore, it is rather likely that the rate for the general population is understated in this age group, for the obvious reason that ihe exact cause of death in the very old is not Table 1?--Comparison of the Actual and Expected Sumbcr of Luna Cancer Deaths by Ape Among Asbestos Miners Planner Total Specified Ait Primary Rut OTtmp per 100.000 30-44 43-M 55-M Dftdoown IS 34 5 <17 A 1 Of>n>d Vo, Effected of Peath* No. or Sft Of Miner* Demin* Proved Tot^l 3.901 1.134 615 313 3 0t 1 I 2 13 2 33 2 45 00 Tb*i(wtfd numror U btifd oo lh av.mtf of th 1044 an! 1244 Kf-ipeelflc rotM tar Ih* Prot in< of Qub*c, f Actually Q 4. 646 Col. IT. June. WeS Af Group 254505---466444.......................................... ................ Totl....... rmvince Number rercentape 711U2S237>6....199r343.T452 ir. U 10 M&.4W 100 pinerCc^onhtoarttc 66 3 100 * Rapport, 19M. a matter of the same intensity of interes as it is in younger persons. A*. Group l*n<t-r 30 30-34 36*39 40*44 45-49 SO-54 5005--64 6750--7649 s:vo7-si SAAll+Alfl 1931-1933 <*.2 <t,9 2-<* 3.0 r..2 1122,.5: l.Vt 10.: 15* 151..42 2.6 Groups of Year? 1V41-1943 02 0.9 3.2 5.4 12 5 r1.6<.9* 33.T 34.5 3fl 6 321074..,639 7.1 195t>l>:r2 1f 0 3> 6* 16 T 37 2 59: T. * 102 3 53 9 59.T Tl.'. U.* Tabic 18 also answers a question pre viously raised. It shows that the members * "Mortality from l,un; Cimrer in Cufu*ia." iwt t'- 19*. of the cohort have >10/ died from lung can increase is particularly marked after :.ge cer at an age earlier than the general popu 50, confirming an observation previou-iy lation, and that such an explanation cannot made, to the effect that until recently lung be offered for the absence of lung cancer cancer has probably been underdiagn> -d in 240 men with more than 40 years of in the older age groups in the general po-. .t- employment referred to on page 643. lation. Before leaving this comparison of the To use these figures for purposes of Province with the miners, it should be comparison, it is necessary to combine the shown that their age distributions are rea rates for certain age groups in order to sonably the same. That this is the case can conform to the age distributions used in th;s be observed from Table 19. study. Since the exact populations in e.-.ch It should be remembered that the miners age group for the years indicated is ivt retire and consequently, it can be expected known, this must be an approximate that the oldest age group will be larger in However, the rates would be somewhat as the general j>opulation. The data presented follows: in Table 20 indicate that the lung cancer rate generally decreases after age 70. There fore, we could expect the rate for ail people over 65 to be smaller than the rate for the Ag Croup 2Mt 45*5-1 55-64 65 Rate 69 00 9? group between 65 and 75, which would apply These rales are. in general. lower t!:.;:i to the oldest group of miners. It is felt those developed for the total < proved and that by using the whole adult male popula suspectedi cases of lung cancer among d'a tion. we have developed rates for the gen asbestos miners-. The only largo difference, eral population which are somewhat lower however, is in the age group of 65 years and than if we had been able to exclude the over, and it is quite possible that the r.ne people in the general population over 75. for this group mav have increased for . A comparison between the asbestos miners Canada between 1952 and 1054 as it did and the population of the Dominion as a for the Province of Quebec 1 Table 17 i. whole was made, using statistical material A further comparison has been made w ::li from several sources. In one source, Phil an over-all rate obtained from the American lips gave age- and sex-specific rates for Cancer Society for respiratory cancer deaths Canada for three periods between 1931 and in Canada in 1953. This rate, for mail-, 1952. The rates for males are given in is 20.S per 100.000. or 5 more per 100.(HX) Table 20. than Phillips' 1950-1952 rate, and compare* 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 Braun--Tnum TEN ' * > U,. I r-U t*, i . /1 * i J j1 r- 647 NOl CUiVlL ri\uivl PPG FJU7bb NOT (SB,VI rrb f ILLS .J .V. A. ARCWITS or jsdlsirial hi.alth Table 21.--.Yi<i*tf'rr of Death.* and Death Rales pet 1(>0,000 by Age Groups for the Adult Male Deputation o) the L titled states* A** Group 20-44 4A-M W-64 + Tout Popul.it i^n 24.M4.W G.iUu.OWi ft.C7u.nuo 44,610,000 Case? Swii G.2M MM ig,m Hate per X 3,C 36.1* 114,3 3T.2 * Du (ram "Vital S(album of tbe Vnlttd iaui," Vol. 1 and 2.1M2. asbestos miners in this study. It is there fore obvious that there are no important differences between the rates for asbestos miners and those for the general population of Quebec and the Dominion of Canada. Since it is probable that figures for the United States are more complete and, there fore, possibly more comparable to the data for the miners, age-specific rates were com puted from "Vital Statistics of the United States," Volumes I and II, for 1952. These rates have been tabulated in Table 21. It is apparent that these rates compare favorably with those for the asbestos miners as shown in Table 8, Still other rates for the United States were obtained from the American Cancer Society, and for males, these were 25.3 per 100,000 in 1953, and 28.0 per 100,000 in 1955. They are not identical with the rate calculated from the figures of the office of Vital Statistics, but this is possibly because the American Can cer Society rates are for males of all ages. Nevertheless, they, too, compare favorably with the rates of 25 (or 34 for total cases) obtaining among the asbestos miners. Turning for a moment to a comparison between the asbestos miners and persons who are exposed to asbestos in one form or another (as distinguished from the gen eral population groups just discused, who have no exposure) an interesting observa tion can be developed by deduction. Hueper J* has stated that there are abo. 35,000 persons exposed in the United States, and we have found that the Canadian mines employ about 8000. Elsewhere, it has been estimated that the workers in England who have exposure total between 3000 and 5000. With workers in Africa, Denmark, Nor- 648 way. and other countries, at lea-t 5<*.n:ji' person* must be exposed throughout the world, and it can be assumed that t!vnumber has been fairly con?t,mt in the 2') years since 1935 when the first ca-e o: asbestosis with lung cancer was reported At least 1,000,000 man-years of exposure has thus been accumulated, and this figure can be divided by the approximately 150 cases of lung cancer with asbestosis re ported during the 20-year period. This gives a rate of 15 per 100,000, which is at least indicative that any lung cancer rate which can be calculated for workers ex posed to asbestos dust is not much greater than that for the unexposed population. Comparison Between Eight Counties Ad jacent to the Asbestos-Producing Areas and Eight Selected Counties.--To compare lung cancer mortality rates in the counties sur rounding the asbestos-producing areas with another group of counties in which no as bestos miners are likely to reside, the rates were computed on the basis of figures for the years 1950 through 1955. The eight counties selected for comparison were Argenteuil, Chateaugay. Montmagny. Porrneuf. Richlieu. Riviere-du-Loup. St. Hyacinthe. and Terrebonne, mainly because they represent a wide geographic distribu tion throughout the Province. The coumie* selected because of their proximity to the asbestos mines include Arthabaska. Eenuce, Drummond, Frontenac. Megantic. Rich 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, based on the adult male population in 152. To emphasize the comparison. Megantic County has been shown separately, as ha? the Province of Quebec and also the Prcn ince with the eight "asbestos-producing counties subtracted. Because of its uniqui lung cancer death rate, Montreal et Isle dJesus has also been listed in order to provid further comparison. It is apparent from the table that tf lung cancsr death rate for the eight courrtu "* r iw 19. [ BB 0005820* r -> * -*** - _-*-** -rfS^SiSias- \ _?V " * fl*V c0 30303 It`-VC C4.VCtf /.V ASBESTOS MINERS Table 22.--S'umher of Lung Cancer Deaths and Rate per lQQfifiO Man-Years Counties Mecamtc County Elf hi `'Adpccm Count!*? Eight *tecc*4 Counties ProtiDOif of UueLer PeoTinop <f QcuotuUnrcctel?ess elfin Momr&al e; Uk de Jesus APdoupMulaMtioanlf 1052 9173.,WU>>"' 1.19&.0V l.i3n0n4.,n0o1n0 1950 3 A z 100 3 1051 13 10 2 317 7 Male Lunc Cancer Death? * IM2 1053 1054 105*. 3 9 2455 3 !< 30IS3 4!1, 303 4 If. 0 is: 23* 287 341 lit IW lb.'. 22S * Ii is usuxsed ttui aU mate lujt| cancer deaths occurred after ace X. T/,laI 1*> M 4i> 1C2( 77t immediately surrounding the asbestos-pro- suggestive of cancer of the lung and in during areas is practically identical with that cluded such diagnoses as media-rinal of eight counties selected for comparison. lymphosarcoma, mesothelioma, cancer <: the While Megantic County has a rate nearly leg with metastases to lung, abscess of lung, twice that of the combined eight selected and cancer of the pancreas. One other was counties, it is lower than the rate for the diagnosed on the basis of x-ray only. In Province, and considerably lower than the addition, there are now living four case.- in rate for Montreal. The figure for Montreal w-hich the diagnostic evidence is strong'y would certainly be higher except for the suggestive of lung cancer. This is a total of very low numbers of deaths reported for 33 cases of all types, including 10 "sus 1950 and 1951, and it would appear that pected" but unproved cases, and 4 that are in those years some error in reporting has still living. The remaining 19 constitute the undoubtedly been made. On the basis of the total of proved cases of cancer of the lung other years, 1950 and 1951 deaths would be among the asbestos miners since 1940. expected to be about 200 greater. This The proved cases averaged 59 years o: would result in a rate of 40 per 100,000. age at death, and varied between 37 years The only possible conclusion from this and 68 years. Their working span covered comparison is that there is no evidence that periods varying from a minimum of 14 the persons who live and work in the coun* years to a maximum of 37 years. On!' ties surrounding and adjacent to the as bestos-producing areas have any greater incidence of lung cancer than those who live elsewhere in the Province. Comment on AH Recorded Lung Cancer Cases, Living and Dead, among the Asbes tos Miners.--Although a simple enumera tion of all the known or suspected cases of cancer of the lung in these areas has no particular value from a statistical point of view, it is of interest to summarize such cases for the record. There were nine deaths prior to the beginning of the time period covered by the study, including one in which the diagnosis was mediastinal lymphosar coma. During the period covered by this three men had less than 25 years of em ployment in the industry. Seven jjmonc those on whom such information is avail able had a weighted exposure placing them in Category III. and six worked in nr. exposure represented by Category I. There were only 17 among these provol lung cancer cases in which we have in formation regarding the presence of asbestosis. Asbestosis was present in nine, although it was minimal in two. Two path ologists disagreed regarding its presence in another. At least seven of the 19 proved lung cancers, therefore, were not accom panied by asbestosis. investigation, there were nine proved cases and three suspected cases in the cohort. Summary and Conclusions Through 1956 and to date in 1957, there Interest in the question of whether there were eight deaths, six of which were merely may be an association bet veen lung cancer Braun--Truan NOTE: THIS DOCUMENT DID 644 NOTCOMEfROM PPG FILE?" ..... ... r;2#S '.- *r^t v?; ca 3'. >304 ,4. A/. ,4 ARCtlll 'L.'t or ISIH STRIA! HkALTi- and exposure to asbestos has been evident since the report in 1935 by Lynch and Smith of a case in which lung cancer and asbes,_tosis were both present. As additional cases in which the two diseases coexisted were reported, a causal association appears to have been gradually accepted by many authors, although some workers considered the correlation to be inconclusive. The pres ent study was undertaken in at) effort to de termine whether a causal relationship did. in fact, exist between exposure to asbestos and cancer of the lung. Since most earlier studies had been limited to enumerating the lung cancers found in certain selected samples, such as cases coming to autopsy or death certificates in which asbestosis was mentioned, it was apparent that they could not fulfill the re quirements of an epidemiological and sta tistical approach to the problem. The present study was. therefore, designed to meet the requirements of this method. After a preliminary survey to explore the availability of reliable information, data were gathered on workers in the asbestos mines in Quebec, based on their medical records. A cohort was defined as a group of asbestos miners having at least five years of exposure and who were in the industry in 1950. Data relative to their characteristics were collected and their status at the end of a six-year period of observation was de termined. In the case of those who had died, an exhaustive search of death certif icates and insurance records was carried out in order to determine 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 str*:**ical methods. Records .vere obtained on 6091 persons who fulfilled the criteria of the cohort. It was nm possible to trace 133 of these for the whole period, but 5771 of the remaining 5958 were found to be still living in 1955 or later. Of the 187 known dead, cancer of the lung was considered to ha\c becn reasonably proved in 9 and to be strongh suggested in 3. The members of the cohort were 'tudivr1 with respect to age, length of employment a weighted average of their exj^surc. and their smoking habits. It was found that 4673 were smokers within the definition o: that term as used in this study. Thirty-four per cent of the cohort were more than 4^^ years of age, and thirty per cent had t<eeT22 U-l employed for longer than 20 vrars. Thin,^ tj per cent had a weighted exposure whicl;-- placed them in the category of highest ex.-< posure. . ra A. The mortality rate for lung cancer, as--- l-v" computed on the basis of nine "proved' deaths among the cohort was 25.3 per 000. When the three "suspected" cases were'."; added, the "total" rate for the cohort rose1*~ w to 33.8. The importance of the suspected; but unproved cases in determining theseW ^ rates has been reiterated because it is likelys--*1 that such cases would not be included ir.;* . the statistics for the general population and;_TM because thev influence the results so mark- CT edly. ' V v i- - 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 th* 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 rate1 650 Vo! IT, Junt* /<><< I BB 0005822 -f- '-T ' - .;^rrr:l --'- '-'$t'rS^-^-*->-y.-- ' ->^vr-sz~'*v >' "^r - W.*- ^*^5 ^ *-^ -- jrl-'H ^ -***0,-**^*j - "irn^r-' WffPE: O^CUMENT DIO ;.<-.Vi7 C.IXCI.R l.X .-ISBCSTOS MIXERS of 37.2, 25.3. and 2S.0 obtained irom various sources for adult males in the L'uiied Slates. Finally, in this matter of comparison. n would appear that the world-wide experience of persons exposed to asbestos dust is not worse with respect to lung cancer than that of the unexposed population. The counties surrounding the asbestosproducing areas, in which it is presumed most of the asbestos miners li\e. have al most identical mortality rates w ith those of eight counties widely scattered through the Province, and are lower than those for the remainder of the Province, and much lower than the rate for Montreal. Since 1940 there have been 19 cases in which the diagnosis of primary cancer of the lung may be considered to have been proved. Approximately half of these cases were associated with asbestosis. All but one died in the recognized "cancer-age" and at least one-third had only the lightest ex posure f Category 11 to asbestos dust. On the basis of what are believed to be complete and reliable data, it seems fair to conclude that the asbestos miners in the Province of Quebec do not have a signif icantly higher death rate from lung cancer than do comparable segments of the general population. Furthermore, the death rate from lung cancer m the areas contiguous to the asbes tos operation- is comparable to that in areas widely scattered throughout the Province of Quebec and is lower than in some urban ized areas within the Province. REFERENCES 1. Alascio E-cobar, R.: Bronchial Carcinoma: Review of 200 Cases. I. Internat, Coll Surgeons 26:375-379 (Sept.) 1056. Z Allen, M. L.: Bronchiogenic Carcinoma As sociated with Pneumonoconiosis: Report of 2 Cases, J. Indust, Hyg. 16:346-347 (Nov.) 1934. 3. Cartier, P : A Contribution to the Study of Asbestosis, Arch. mal. profess. 10:589-595, 1949. 4. Anderson. C. S., and Dible, J. H.: Silicosis and Carcinoma of the Lung, .1. Hyg. 38:185-204 (March) 1938. 5. Baader, E. W,: Asbestosis, Deutsche med. Wchnsehr. 65 407-108 (March 17) 1939. Braun--Truan NQIXOMEffiSE p.?FiLK Srhwc:/ /t-clir allg Path. 14:275-2'C. PM 7. Behren-, \V,, Jr.: The Clinical i.-'i Palliiii.'us of Aslicstosi*. Ztsclir. 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