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FILE NAME Corning OC DATE 1964 Apr 6 DOC OC172 DOCUMENT DESCRIPTION Medical Journal Article - Asbestos Exposure and Neoplasia wee eres eRplid UY, 1849 Asbestos Exposure and Neoplasia Irving J. Selikoff MD Jacob Churg MD and E. Cuyler Hammond DSc New York 00145 Building trades insulation workers have relatively light intermittent exposure to asbestos Of 632 insulation workers who entered the trade before 1943 and were traced through 1962 forty died of cancer of the lung or pleura whereas only 6.6 such deaths were expected Three of the pleural tumors were mesotheliomas there was also one peritoneal mesothelio ma Four mesotheliomas in a total of 255 deaths is an exceedingly high incidence for such a rare tumor In addition an unex pectedly large number of men died of can- cer of the stomacli colon or rectum 29 compared with 9.4 expected Other cancers were not increased 20.5 were expected 21 occurred Twelve men died of asbestosis LTHOUGH PULMONARY CARCINOMA had been observed in the earliest studies of ashes- tosis association between the two conditions was first suggested by Lynch and Smith in 1935. Ad- ditional reports of such association followed Per- haps the most striking data was presented in the annual report of the Chief Inspector of Factories of Great Britain for 1955. Every death with asestosis in the files of the Factory Department from the 5rst recognition of asbestosis as a disease entity was studied Altogethet 365 such deaths were recorded 1924-1955 Sixty or 17.8 were found to be accompanied by cancer of the lung or pleura Doll after reviewing the problem and adding data of his own concluded that lung cancer was a specific industnal hazard of heavily exposed asbestos workers Nevertheless some investigators have held that while these observations observations might be suggestive they did not establish an increased incidence of carci- noma of the lung in pulmonary asbestosis and further that the association was unproved The factor of selection was considered a poten- tial weakness in evaluating reports of autopsy series It was noted that complicated and unusual cases would be more likely to come to autopsy thus raising the apparent frequency of associated Jung neoplasms Further it was argued that autopsy statistics which dealt with particular groups of those who died do not reflect total populations of asbestos workers Additional reservations were based on the frequent absence of data regarding From the Division of Thoracic Disease Department of Medione Lnd the Department of Pathulog Mount Sinai Hospital Read before a joint meeting of the sections on radiology and me the chest and the Amenian College of Chest Physicians at the 2th Annual Meeting of uity NJ June 17 1963 the Agencan Medical Association Atlantic ( er or - exposure smoking habits and personal history on the size of series and on inadequate histological verification in some cases Within the last few years a number of additional problems connected with asbestos exposure have appeared making clarification and resolution of the foregoing statistical incertainty a matter of considerable concern First there has been greatly increased use of the various types of asbestos a fold increase in world utilization of this group of minerals from 500,000 tons to 2,500,000 tons per year in the last 30 years as well as a greatly increased number and variety of industrial applica- tions of asbestos over 3,000 such uses now recorded Second suspicion has been growing that malignancy associated with asbestos exposure may include neoplasms other than carcinoma of the lung Thus a significant relationship has been claimed between diffuse mesothehoma of the pleura and peritoneum and asbestos exposure This communication is concerned with investi. gations undertaken to study the following factors 1 the medence of deaths due to pulmonary carcinoma among a group of workers exposed to as- bestos under United States industrial conditions in the past several decades 2 whether or not such individuals would also be found to have an increased risk of other neoplasms and 3 whether such risks would be present in an industry other than the producing or products industries with which most reports in the past have been concerned but which would not nec- essarily represent the most important areas of as- bestos exposure at this time Further it was hoped that study of an industry with asbestos exposure of limited extent and intensity would throw some light on the potential problems associated with minimal exposure to asbestos Materials and Methods Our investigations have been concerned with 1,522 members of the Asbestos Workers Union in the New York metropolitan area members of New York Local 12 and Newark NJ Local 32 of the International Association of Heat and Frost Insu- lators and Asbestos Workers As the full title im- plies these men are insulation workers Although the union is considered one of the building unions its members do insulation work in a va- riety of industries including shipbuilding Called laggers in Great Britain they are often desig- nated pipe coverers insulators or asbestos workers in this country The union is one of the oldest in the country 142 97 Vol 185 No 1 7 yess Rewer ewew ert The New York local as the SalamantdheerfirAstssuonciioan- n of Boiler and Pipe Felters was United States It amal sulation workers in the the current Asbestos ated with other locals as of this union Union in 1912. The stability arkers reflected in the stability of its member has breoelnls Once a pipecoverer always a pipecov of Experience of 632 Asbestos Table Years Dust 20 Years or Longer Asbestos Workers Exposed to [ ao Age 35 39 86-- 40.44 ie . 4549 4, 50 ++ 59 .. 19431947 850 230 339 391 382 Years ~ 1948 1952 1650 4865 324 364 390 1953 1957 70 29 5 5300 308 0 3160 344 ~ 1958 1962 110 70 314 502 268 5 2550 epidemiological dup been of importance to us 60 221 341 181.0 2860 280 dup has ae of men particularly suit- 65 69 ..... 1390 830 1155 1370 1975 * and has made this group effects of asbes- 70-74 ee 315 700 705 750 235 able for the study of l uno skinllg ed workers exposed 79 84 .. .... 80 185 385 55 135 20 Unlike tos inhalation in among 41 RES RES 85- wae 35 1,9120 ZX780 7,3365 2,011.0 to asbestos inuation insulation Totals csuueneee there is little labor turnover raemcoorndgs are main Accurate employment 339 had been exposed to as- Of these 632 men words as of Jan workers which has also been con- tained by the union bestos dust prior to 1924. In other since these with health problems in the industry 1 1943 20 years or longer had elapsed 293 cerned trade was badly hit during the depression exposure The and very few were 339 men were first reached the exposed The remaining point had to drop out some men the 1930's By the end of 1942 the men time after Jan 1 1943 and before the end added during consisted mainly of men with consid union rolls few who joined in 1940 at some who were first exposed pnor of 1962. The 339 men of the 20 years or counted in each erable experience plus a 1946 and 1962 union to 1929 were of death of those who died The 1941 and 1942. Between up to the time in 1924 or later were substantially membership D inca reat seda union records a list was member 293 who were first exposed only after they reached the years who died being dropped Source of founted prepared of every individual who was a Dec 31 exposure point thoseWhen the statistics were of either of the metropolitan locals on between that date and Dec 31 at the time offoduenadtthhat we had records covering completed we of men 1942 or who joined whatever his subse- No one was omitted a total of 8,737.5 years of experience first 1962. work history The 1942 list included 632 with a history of 20 years or longer since quent en 590 men joined after 1942 from union records dust to asbestos exposure 1912.0 were in the five- Of the 8,737.5 years Personal data were obtained of each man was detailed 1943-1947 2,478.0 were in the penod nd the work history including withdrawal frormetiermepmleonytmeilnltnewsas rThseesre- year period in the period 1953-1957 1945-1952 2,336.5 were 1955-1962 Table 1 in the period vice other employment of the onset and 2,011.0 were of the years in data gave the baseline for calculation who had shows the age distribution Table 2 shows 1 and duration of exposure For members Fund each of these year peridoedasth rates of all US died records of the Health and Welfare prodeath date and place of death Copies of the average specific each of these periods and 2 white males during of vided were obtained on all but one of them the average specific death rates from cancer certificates protocols Autopsy histological specimens and hosobtained and reviewed in those mediastinum and trachea among the wlhuintge pmlaeluersadunng each period as reported by pdietaalthrsecaoprpdsrow xiemraetely one half in which the terin a hospital US the US National Office of Vital Statistics were then multiplied by the cor- minal illness had occurred studies have sug- The years US death rates to ascertain Statistical Previous responding with asbestosis sel- reported of deaths under the null gested that neoplasia associated to as- the expected number of asbestos workers dom occurs until 20 years after first exposure the hypothesis that the death rates of all US white bestos dust Therefore we decided limit an exposure do not differ from death rates taken into consid- males both age and date being in Table 3 analysis to men with such history Our complete records caonvder raelbl remdemm be em rs- eration The results are summarized of the union including active Results bers both dead and alive during the31ye1a 96r2 first five 1943- period from Jan 1 1943 through Dec with Total Deaths During the years the asbestos However with few exceptions the only men since first exposure 1947 only 28 deaths occurred among whereas 39.7 deaths would have occurred a history of 20 yetahres 6o3r2 lmoe ngneron the union rolls as asbestos were workers death rates been the same had their specific to were a few men of 1 1943. The exceptions for all US white males during those years Ta- Jan the union after Jan 1 1943 but who as In other words at the start of the study who joinedemployed previously as asbestos workers had been 255 died before Jan ble 3 death the asbestos workers had below average such This is by no means surprising Indeed elsewhere Of these 632 men rates 1,1963 1,1963 143 98 om 24 ' Table Total Deaths and ASBESTOS EXPOSURE ET AL Deaths From Cancer of the Lung Bronchus Pleura per 10,000 White Males per Year JAMA April 6 Mediastinum and Trachea 1964 { < ree ae na FO? A - F- 35 Ago 35 4044 i, 4549 50'5 ce isscuees wc, 59 te 60-64 en 65 69 70 75.79 5 84 250 1943-1947 A Total 36 55 Lung Cancert * 1 85 2 133 4 196 S 295 ? 7 6 . 6 5 3 1948-1952 A Total 30 Cancert Lung Cancert .. 48 i 7B 3 124 5 189 8 281 10 417 11 605 11 915 10 7.253 4 8.162 ? 1953-1957 1953-1957 Total o Lung Cancert 26 vase 43 1 72 3 115 6 178 10 276 14 416 17 586 16 878 14 1.346 12 2.817 1958-1962 1958-1962 Total Lung Cancere 25 i 42 1 70 3 116 7 178 11 272 17 418 21 607 21 866 17 > 1363 21 1 Death rates as reported annually for 1955 1962 is a by the projection of 1958 1960 1Death rates include cancer of the lung 8 2.148 Vita US National Office of Statistics A five year average is since 1961 1962 rates are not yet available given here branchus pleura mediastinum and trachda assigned to international for list each code 31 period Average No. 47b prior * ' s ! ' is almost always found in the first few years of a prospective epidemiological study of this type The explanation is almost certainly as follows The 632 men in this analysis were actively employed as as- bestos workers in 1942 Since disability from illness or other causes precludes employment in a trade of this type these men were at least not disabled at the presumably start of well or riod Almost the study pe- any group so selected as to exclude the ill and disabled has a lower death the ensuing few years than does the rate dunng lation since ill and disabled general popu- persons have extreme ly high death rates A selective effect of this gradually wears off with time and largely ditsyapp-e pears within five to ten years from the time of in- itial selection During the death the second year period 1948-1952 rate of the asbestos workers was slight- ly higher than the death rate of all US white males ie 54 observed deaths compared with 50.5 ex- pected deaths In later periods the death rate of the asbestos workers was For the period 1953-1957 tphreorpeorwteiroenat8e5lyobhsiegrhveerd deaths compared with 566 for the period 1955-1962 theerxepewcetreed 5d5eaotbhsseravendd deaths compared with only 54.4 expected deaths Table Observed and Expected Number of Deaths Among 632 Asbestos Workers Exposed to Asbestos Dust 20 Years or Longer Cause Cause of Death Death Total all causes - 1943 1947 workers 28 Expected Observed asbestos Expected US workers white malmeasles white Total ali 39.7 39.7 Years 19481952 19571957 54 85 50 566 1958- Total 1962 1962 88 255 544 203 Cancer of the Lung Pleura and Trachea -In each of the four year periods far more deaths from cancer of the lung and pleura occurred .* 7, - would among the asbestos workers than would have occurred had their death rates from these diseases been the same as for all US white males Table 3 Altogether 45 of the 632 asbestos workers died of cancer of these sites whereas only 66 such deaths be expected from general US experience Of these 45 deaths 42 were recorded as due to bronchogenic carcinoma and 3 to neoplasms of the pleura The pleural neoplasms were all recorded . Vr. 3 2 \ ov . < as mesotheliomas . ) Thus it was found that the death rate from can- cer of the bronchus and pleura was 68 times as x high among these asbestos workers " eral US wine as the gen ,> \ . male population both and date vs age br. being taken into '' consideration rate the high may be asked whether rate of lung Cvs cancer among these asbestos workers y pos- 4.5.9 could sibly be attributed to an unusually large proportion 4.5.9 of cigarette smokers among them We cannot an- swer this question directly since we have been able to not yet ascertain the smoking habits of the men who died However the following pieces of evidence indicate that unusual smoking habits can- not account for the high death rate from lung can- cer amoang mong thesthese e workers workers $ 4.5.9 workers We have interviewed 320 of the 377 members of the 1942 surviving group Table 4 gives a sum- mary of the smoking habits in this with a sample of men drawn group compared from the population of Thge eneral ion population population sample include counties 1,1,112211 counties counties is somewhat in 25 in statses tastattees s inadequate since The un- un- it does . wr . ^> 1 -< - ExpectedObsExeprecvteedd wahsibt esetomsal woers kers of Cancer lung and pieura Expected workers Cancer of stomach colon and rectum Observed Expected : fasbestos workers US white males Cancer of all other artes com 13 26 3.7 6 8S 130 13 0.8 ia 2.0 - 2.0 2.5 > 2.6 ( Obseralvled ) Observed asbestoassbestos worworkkersers 0 Expected US white males ' Asbestosis . Observed asbestos workers weet ne . 20 20 - 42 i 6 4 4 39 9.7 18 2.4 23 14 6.0 7 95 not include the men who didied ed and does not iin- n- 365 clude all the present the living 45 union of present Nevertheless it living living members members members of shows that a substantial 6.6 proportion of asbestos workers never smoked rseis ttes regularly Certainly the 632 men in our anciaglay- 9.4 sis of death rates were not all cigarette heavy smokers cigarette . smokers 21 20.3 12 In the general male population population cancer high death rates are about ten ttiimes mes as among cigarette smokers as among nonsmokers and the FUT 100 re 4 ASBESTOS SELIKOFF ET AL . tape Table Smoking Habits of 320 25 Abestos Workers Exposed to Asbestos Dust Compared With Sample of Men From the General Population20 Years or Longer Never Smoked t Asbestos Workers Age4049% 4049 93 5559 143 6069 20.3 70+ 25.5 Regularly stn General Population % 18.8 199 23 37.1 Sample of man from general population as reported ,r Smoked Pipe Cigar Naver Cigarettes cd Cigarettes Asbestos Workers % in, General Population . % 46 7.5 6.1 8.9 10.1 11.8 162 239 by Hammond and Carfinuel History Cigarette im -. Aubestos Workers % 861 796 69 62.7 of Smoking General Population % 73.7 702 60 390 death rate from lung cancer increases the amount of greatly with * cigarette smoking However a large proportion of all men in the United States have history of regular cigarette smoking From data a in a prospective study on smoking it may be esti- mated that if all men smoked a pack or more of cigarettes a day ie if all the nonsmokers cigar smokers pipe smokers and light cigarette smok- ers had instead been heavy cigarette smokers the cancer death rate would be approximately 3.4 times as high as it is at this time From this we may conclude that even if all asbestos workers had smoked our a pack or more of cigarettes a day and indeed from our know they did not and if sample we were of no exposure to asbestos significance then their lung cancer death rate would have been about 3.4 high as the rate in the times as general US male popula- tion Clearly workers the smoking habits of the asbestos . cannot account for the fact that their lung cancer death rate was 6.8 times as high as that of white males in the general population Gastrointestinal the death Cancer to our surprise rate from cancer of the stomach and the death rate from cancer of the colon and rectum were higher among the asbestos workers than would be expected from the rates US white male reported for the population calculated in the same way as for lung cancer Twelve deaths from cancer occurred gastric among the asbestos workers as compared with only 4.3 expected Seventeen deaths from cancer of the colon and rectum occurred among the asbestos workers as compared with 5.2 expected Cancer of All Other Sites The combined death rate from cancer of all sites other than pleura and stomach colon and lung and increased Twenty such deaths roeccctururmedwas not asbestos workers as compared with 20.5 among Asbestosis the 255 expected deaths 12 were due to asbestosis ( pulmonary insufficiency cor pulmo nale The lapsed time from first asbestos to death from asbestosis exposure averaged 45.8 years with a range of 32 to 59 years Comment Carcinoma of the Lung results with to carcinoma of the lung are clear regard Industrial ex- Altogether posure to asbestos by insulation workers as stud ied here results in a marked increase in the inci- dence of cancer of the lung approximately six to seven times the expected incidence 45 1767 1767 of 255 men with more 20 than years elapsed elapsed since the onset died of lung or pleura of exposure of cancer These data do not give the incidence of of the lung in asbestosis cancer cific conditions of They relate to the spe our investigation to a group of men with only intermittent exposure to materials containing limited amounts often % to 20 of asbestos under working conditions varying from very dusty as in extracting old insulation in closed quarters to those with little dust exposure as in building construction in open air Moreover they relate to the relatively recent past in a trade with the shorter work week of the strong building trades unions in an era when industry has been aware of potential asbestos hazard and the working popu lation has had some consciousness of potential risk associated with dust exposure These data would not necessarily apply to asbestos in other industries such as the factory proedxupcotsiuorne of asbestos products the ashestos textile industry etc where conditions of employment might be quite different Our results do not contradict the even higher incidence of lung cancer suggested in other studies ; they are merely a shade less strik- ing Determining Diffuse Pleural and Peritoneal Malignancy- Mesothelioma the incidence of dif- fuse pleural mesothelioma is complicated by the insecurity of its histological verification While some pathologists will so categorize a high propor- tion of diffuse pleural tumors in the experience of others it is a very rare tumor and may be mim icked by anaplastic peripheral carcinoma of the Jung and diffuse brosarcoma of the pleura It is difficult to evaluate completely the published re- ports of diffuse pleural mesothelioma in asbestosis in the absence of complete details of each case To the present time there has been no informa- tion concerning the incidence of diffuse pleural mesothelioma in asbestosis since the published cases are reported without reference to a total ulation in which they occur Nevertheless potph-e 145 100 * growing number of reports of individual cases Co suggests that these tumors are perhaps becoming relatively frequent complications of asbestos ex- osure ( Our observations in this series are similarly sug_ gestive In three of the 255 deaths among the men who had worked for 20 years or more the exam- ( ining pathologist considered the death due to dif- fuse pleural mesothelioma and in the two cases in which we have been able to review the histological material the histological appearance was that of ten so categorized and asbestos bodies were pres ent This incidence of more than % of deaths from pleural mesothelioma is strikingly high for a tumor which is generally considered to be extreme- ly rare In one case in our series pathological examination suggested diffuse peritoneal mesotheli oma This single experience is too fragmentary for evaluation Gastrointestinal Carcinoma instances of gastrointestinal carcinoma in the presence of as- bestosis have been known but there have been no data to indicate that these were more than coinci- dental findings Among the asbestos workers studied here cancer of the stomach colon and rectum was three times as frequent as expected These data suggest that there may perhaps be an etiological relationship between industrial asbestos exposure and carcinoma of the gastrointestinal : tract Environmental Asbestos Exposure recent fi Demonstration by South Africanperitoneal and British in- vestigators of pleural and peritoneal neoplasms among individuals who had chance environmental exposure to asbestos many years before raises the very important question of possible widespread carcinogenic air pollution The possibility of environmental exposure has long been known Soon after the initial clarification of asbestosis as a clinic entity Haddow 10 demonstrated asbestos bodies in a man not employed in the industry but living next door to an asbestos factory This finding was later mirrored in the finding of chronic beryllium dis- ease among residents of a community near a beryl lium factory What is new however is an appre- ciation of the potential extent of the problem Thomson and " associates have reported the fre- quent findings of asbestos bodies in the lungs of urban dwellers Among 6,312 individuals rayed in an area about an asbestos mine in Finland Kiviluoto 3 found 499 cases of pleural calcification of the type characteristically seen among asbestos workers without obvious use in a paperable area without any asbestos mine no cases were found among 7,101 persons rayed It should be noted that these were not people who worked in the mine but rather were farmers housewives and others who lived in the general location In one subject who came to autopsy polarized microscopy demonstrated asbestos fibers in the lung Similarly the lung of a cow grazing near the mine also showed the presence of asbestos A particular variety of environmental exposure may be of even greater concern Asbestos exposure in industry will not be limited to the particular craft that utilizes the material The floating fibers do not respect job classifications Thus for example insulation workers undoubtedly share their exposure with their workmates in other trades intimate contact with asbestos is possible for elec- tricians plumbers metal workers steamSt- ters laborers carpenters boiler makers and fore- men perhaps even the supervising architect should be included 1 E 100th St New York 10029 Dr. Selikoff This study was supported by the Health Research Coun- al of the City of New York executive Cooperating in this investigation were the executive of ficers of the International Association of Heat and Frost Insulators and Asbestos Workers Washington DC and the officers and membership of the New York and Newark NJ locals of this Union References 1. Lynch K.M. and Smith WA Pulmonary Asbestosis Carcinoma of Lung in Silicosis Amer ) Cancer 24.56-64 May 1935 2. Annual Report of Chief Inspector of Factories for Year 1955 London Her Majesty's Stationery Office 1956 ennd 8 p 200 3. Doll .. Mortality From Lung Cancer in Asbestos Workers Brit ) Industr Med 61-86 1955 4. Bohl~-g H and Jacob C Neue Gesichtspunkte ^...ber den Lungenkrebs der Asbestarbeiter Deutsch Med Wschr 231-233 Feb 17 1956 5. Braun D.C. and Truan T.D Epidemiological Study of Lung Cancer in Asbestos Miners AMA Arch Industr Health 17.634-653 June 1958 8 Wagner ] C Sleggs CA and Marchand .: Difuse Pleural Mesothelioma and Asbestos Exposure in North Western Cape Province Brut } Industr Med 260-271 7. Hammond C. and Carfinkel L Smoking Habits of Men and Women ] Nat Cancer Inst 416-442 Aug 1661 8. Hammond E.C. and Horn D Smoking and Death Rates Report on Forty Months of Follow of 187 783 Men I. Total Mortality II Death Rates by Cause JAMA 1159-1172 March 8 1294-1308 March 15 1958 9. McCaughey W.T.E Wade O.L and Elmes P.C Exposure to Asbestos Dust and Diffuse Pleural Mesothelso- mas Brit Med J 2.1397 Nov 24 1962 10 Haddow C. in Report of Annual Meeting of British Medical Association Manchester 1929 Lancet 230-231 Aug 3 1929 11. Chesner C Chronic Pulmonary Granulomatosis in Residents of Community Near Beryllium Plant Three Autopsied Cases Ann Intern Med 32 1025-1045 June 1950 12. Thomson J.C. Kaschula ROC and MacDonald R.R Asbestos as dera Urban Hazard $ Afr Med 77-51 Jan 18 1963 13. Kiviluoto R Pleural Calcification es Roentgenologic Sign of Occupational Endemic Authophyllite tosis Acto Radiol Suppl 194 pp 1-67 1980 146