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FILE NAME Brakes BRK DATE 1983 Oct DOC BRK082 DOCUMENT DESCRIPTION Journal Article - Mesothelioma in CT 1955-1977 - Journal of Occupational Medicine Reprinted from Journal of Occupational Medicine Volume 25 No. 10 October 1983 ee Mesothelioma in Connecticut 1955-1977 Occupational and Geographic Associations Mary Jane Teta M.P.H Hilton C. Lewinsohn M.B. B.Ch J. Wister Meigs M.D Romeo A. Vidone M.D Linda Z. Mowad R.N and John T. Flannery B.A. All cases of malignant mesothelioma 201 and other primary malignant pleural tumors 19 reported to the Connecticut Tumor Registry from 1955 through 1977 were studied in an attempt to identify high jobs industries and geographic locations and to estimate the risk attributable to asbestos exposure in the workplace Data were obtained from hospital records death certificates and city directories for cases case spouses and a random sample 604 of Connecticut decedents 1955-1975 Three cases involved histories of work in asbestos products manufac ture but there was no evidence of residential risk in that geographic area Relative risk RR for carpenters and cabinetmakers was 2.25 p < .05 for plumbers and pipe- fitters 3.87 p < .05 and for persons ever employeidn the rubber industry 5.08 p < .01 Occupational exposure was indicated in 85 of the cases attributable risk AR was 36 Risk increased with greater exposure and older age AR was 81 in men aged 70 to 89 years at diagnosis Reduction of unnecessary occupational asbestos exposure remains the highest public health priority In 1980 Lewinsohn et al described mesothelioma in Connecticut from 1935 through 1977. Problems ofdiagno- sis and ascertainment made results for the years prior to From the Yale School of Epidemiology and Public Health New Haven Conn Ms. Teta Associate in Research Connecticut Cancer Epidemiology Unit Dr. Meigs Clinical Professor of Epidemiology and Public Health and Ms. Mowad Associate in Research the Union Carbide Corporation Danbury Conn Dr. Lewinsohn Assistant Corporate Medical Director the Yale University School of Medicine Dr. Vidone Associate Clinical Professor of Pathology and the Connecticut Tumor Registry Connecticut State Department of Health Services Hartford Mr. Flannery Director Ms. Teta is now affiliated with Union Carbide Corporation Danbury Conn Address correspondence to Union Carbide Corporation Health Safety and Environmental Affairs Dept. P2 1 Ridgebury Rd Danbury CT 06817 Ms. Teta This investigation was supported by grants 33235 and 61002 awarded by the National Cancer Institute US Department of Health and Human Services and by the Institute of Occupational Medicine and Hygiene Yale University School of Medicine 1955 of uncertain value From 1955 through 1977 the adjusted rates among males rose from about 0.19 to 100,000 and among females from 0.13 to 0.19 100,000 Bruckman et al claimed in 1977 that increases in the disease are due to the increase in the cumulative asbestos consumption and that emissions into the environment e.g. building construction demolition automobile brake linings are somehow involved as causative factors The substantial rise however in the female ratio is more consistent with occupational exposures of men at work Bruckman et al were unable to provide complete occupational histories for the 133 diagnosed cases of mesothelioma 1935-1972 drawn from the Connecticut Tumor Registry CTR on which their report was based Despite this limitation the Air Compliance Unit of the Connecticut Department of Environmental Protection has proposed an ambient air standard of 30 m measured over a day interval This proposal was based on estimated asbestos concentrations at several selected sites in Connecticut Mesothelioma is a rare disease with approximately 2.2 cases per million population expected annually.4 The proportion of cases not associated with some form of asbestos exposure has been reported to be near .5-7 This disease may serve as a marker for unsuspected past asbestos exposure The present study was designed primarily to examine the job categories and industry titles of identified cases of malignant mesothelioma recorded in the CTR in an attempt to ) identify job categories industries specific employers and Connecticut geographic locations that are associated with an excess risk for meso- thelioma and that may also be associated with asbestos usage and 2 determine the proportion of cases involving possible exposure to asbestos in the workplace . The health implications of the proposed ambient air standard make it desirable to estimate the kinds and num- bers of cases that may be due to occupational asbestos exposure other as yet undetermined risk factors or possible asbestos exposure from the general environment There remain numerous unanswered questions concern ing the existence of a threshold and the nature of the as- Journal of Occupational Medicine 25 No. October 1983 749 4 mesothelioma response relationship.8.9 The data available allowed us to approach these problems indirectly In lieu of dust measurements job and industry titles ascertained for study subjects for periods up to 50 years were used as indicators of exposure Methodology Since mesothelioma has often been confused with other malignant tumors an anatomic pathology review of all cases reported to the CTR between 1955 and 1977 was undertaken Histologic material along with gross autopsy and clinical reports was submitted to one of us R.A.V. for review No personal identifiers or occupational data were included Although the final results of this review will be published separately specific findings will be discussed in the context of the present report The CTR registered 196 cases of primary malignant mesothelioma during the years 1955 to 1977 inclusive With the exception of the Veterans Administration VA Hospitals in Connecticut it is mandatory for hospitals to report diagnosed malignant neoplasms to the central registry A review of all autopsy records from the larger of the two VA hospitals in the state from 1955 through 1977 yielded five additional cases of mesothelioma bringing the total number to 201. This included 137 cases with site pleura 29 with site peritoneum and 35 of other or unknown sites Concerns about diagnostic sensitivity prompted the inclusion of 19 cases reported as pleural tumors other than mesothelioma during the same year period These concerns were justified by the slide review that identified several cases of mesothelioma in this group The total case study population size was 220 Table ) Medical demographic and occupational data have been collected for these 220 cases Similar information was gathered by Roush et al10 for a computer random sample of 604 decedents 1955-1975 aged 20 to 98 Table 1- 1- Sex Age and Diagnostic Classification of 201 Cases of Malignant Mesothelioma and 19 Other Pleural Tumors Diagnosed in Connecticut 1955-1977 Diagnosis Males Females Total Mean Age Pleural 100 37 137 63 , mesothelioma Pleural tumor 11 8 19 63 other than mesothelioma Peritoneal 18 11 29 59 mesothelioma Mesothelioma at 21 14 35 54 other sites and at unknown sites Total 150 70 220 61 World Health Organization 1976 as originally recorded by CTR At diagnosis 750 years who provided a control group These controls were drawn without stratification of any kind from the death certificate files of the Division of Health Statistics of the Connecticut State Department of Health Services CSDHS Death certificates DCs provided demographic data and usual occupation for study subjects at time of death City directories CDs were searched for residential and employ ment histories , 10 20 25 30 40 and 50 years prior to date of diagnosis or death provided that the subject was at least 20 years old at the time The Price and Lee City Directories which are available for about two thirds of Connecticut towns from 1890 to 1980 have a target population of 92 of the adult males in the state A similar occupational history and cancer search was conducted for all spouses n = 193 of the 220 cases to explore the possibilities for domestic exposure that may have originated in the workplace The three 1970 U.S. Census industrial and occupa- tional codes were assigned to the employment information ascertained Industrial coding was determined on the basis of product descriptions for each employer which were found in the manufacturing directories of Connecticut published by the State Department of Labor and in the Price and Lee directories for nonmanufacturing industrie1s3 The study population for occupational analysis was restricted to males over 30 years of age at death or diagnosis A large proportion of females 46 cases 31 controls had no known work history Although occupational etiologies may be a possibility the absence of reliable occupational data for females prevented a formal analysis of their occupational asbestos exposure Since all cases were born after 1874 controls born prior to 1875 were excluded There remained 611 male subjects for the occupa tional analysis 136 mesothelioma cases 11 cases of pleural tumors other than mesothelioma and 464 controls The control ratio was approximately 3 Seven cases included in the analysis were those of individuals who were alive at the time of the data collection period 1978 Study subjects were first compared on the basis of whether they had ever worked in selected jobs or industries with known potential for occupational asbestos ex- posure or for which there were sufficient numbers to be informative Formal statistical comparisons were made for seven job categories engineers brickmasons and stone- masons cabinetmakers and carpenters electricians foremen painters construction and maintenance workers and plumbers and pipefitters and for eight industry categories construction miscellaneous nonmetallic mineral and stone products electrical machinery equipment and supplies aircraft and parts ship and boat building yarn thread and fabric mills rubber product and automobile repair and related service The Haenszel odds ratio was used to estimate relative risk RR To increase statistical power and provide a more direct measure of causation efforts were made to classify study stubjects in terins of the probability of occupational asbestos exposure A subset of jobs and another subset of in- dustries were selected for which exposure to asbestos was considered either possible or likely Tables 2 and 3 These subsets were developed by one of us H.C.L. without reference to information about disease status Comparisons of control proportions with occupational asbestos Mesothelioma in Connecticut et al Table 2- 2- Estimates of the Probability of Asbestos Exposures Exposures in Two Categories by U.S. Cents Code and Job Title Table 3 Estimate of the Probability of Asbestos Exposaret in Two Categories by S. Consus Cads and Industry Title US Convers Code Likaty Job Title 012 Electrical and electronic engineer 013 Industrial engineer 014 404 =Mechanical engineer Boilermaker -486 522 = Railroad and car shop Plumbers and pipefitters 525 534 = Power station operator Roofers and staters 601 615 = Asbestos and insulation workers Dry wall installers and lathers 622 Furnacemen tmelter men and pourers 751 Construction laborers excluding carpenter helpers Category US Cantus Code Possible Job Title 006 011 022 023 056 140 142 151 = Aeronautical and astronautical engineer Civil engineer Sales engineer Engineer = Personnel and labor relations workers = Teachers college and university Elementary school teachers Chemical technicians 152 Oralismen 173 190 216 221 326 Technicians nec = Painters and sculptors Managers and superintendents building Officers pilots and pursers ship Insurance adjusters examiners and investigators 403 410 Blacksmiths Brickmasons and stonemasons 413 Cabinetmakers 415 Carpenters 424 Cranemen derrickman haistmen 430 +433 436 'Electricians 0 Electric power linemen and cablemen Excavating grading and road machine operators exc bulldoze 441 442 446 454 Foreman ne.C. Forgemen and hammermen Heat treaters annealers and temperers Job and die setters metal 455 461 471 +473 481 482 = Locomotive engineer Machinists Mechanics and repairmen aircraft Automobile mechanics Heavy equipment equipment mechanics including diesel Household appliance and accessory installers and mechanics 483 492 495 502 503 510 514 533 535 Loom fixers Miscellaneous mechanics and repairmen mechanics =Not specified 9 Millwrights Molders matat and reparmen Painters construction and maintenance Pattern and model makers excluding paper Rollers and finishers metal Sheetmetal workers and tinsmiths 545 550 552 561 610 Stationary engineers Structural metal craftsmen Telephone installers and repairmen = Tool and die makers Checkers examiners and inspectors 611 621 623 641 650 651 61 662 1670 1672 1673 1674 1680 1681 690 694 69 710 753 760 944 manufacturing Clothing ironers and pressers Filers polishers sanders buffers Garage workers and gas station attendants Mixing operatives Drill press operatives Grinding machine operatives Sailors and deckfands Sawyers Carding lapping and combing operatives Spinners twisters and winders Weavers Textile operatives C. Welders and cutters Winding operatives n.e.c. Machine operatives muscellaneous specified =Miscellaneous operatives =Not specified operatives Motormen mine factory logging camp etc. Freight and material handlers Longshoremen and stevedores Hardresters and cosmetologist An identified reference in sources as having potential for asbestos exposure of actually described in conjunction with case in the literature Occupations in textile factories that need further investigation to determine whether asbestos lextries were involved as distinct from cation wool ar manmade fibers nec not otherwise classified exposure possible and likely were analyzed separately for each of three sources of information - job title industry title and job title and industry title For each of these comparisons adjustment was made nonsimultaneously for age 30 to 49 years 50 to 69 years 70 to 89 years year of . ene US Census Code Likely Industry Title Category S. Conces Cado Possible Industry Title 057 Nonmetallic mining and quarrying excrot fuel 8882 8882 8882 138 22 147 = General building contractors =General contractors except building = Special trade contractors =Miscellaneous nonmetallic mineral and stone products Blast furnances steel works rolling and finishing mills Other primery iron and steel industries 998 998 998 Primary aluminum industries Other primary nonferrous industries Miscellaneous fabricated metal products 177 Engines and turbines 199 Household appliances 588 Radio TV and communication 2 2 22 22 equipment Electrical machinery equipment and supplies nec Not specified electrical machinery equipment and supplies Aircraft and parts Shipbuilding and boat building and 229 239 repairing Railroad locomotives and equipment Scientific and controlling instruments 86622 457 86622 86622 539 = Ordnance Electric light and power Water supply Electrical goods - wholesale Machinery equipment and supplies - wholesale 263 263 569 607 Petroleum products - wholesale = Paper and its products - wholesale Lumber and construction - materials wholesale Lumber and building material 833 833 668 retailing = Motor vehicle dealers Tite battery and accessory dealers Household appliances TV and radio stores 22 22 Automobile repair and related services Laundering cleaning and other 917 927 937 garment services Federal public administration State public administration Local public administration 127 Cement concrete gypsum and plaster products 128 Structural clay products 158 Fabricated structural metal products 289 Be-verage industries 318 Miscellaneous textile mill products 328 337 = Pulp paper and paperboard mills Peperboard containers and boxes 348 Plastics synthetics and resins excluding fibers 379 Rubber products 407 417 = Railroads and railway express service Trucking service 419 Water transportation 427 567 609 Amr transportation Alcoholic beverages - wholesale Department and mail order establishments 627 MiscelaneousMiscellaneous general merchandise stores 648 Gasoline service stations 649 Miscellaneous vehicle dealers 758 Electrical repair shops 759 857 Miscellaneous repair services Elementary and secondary schools 858 867 Colleges and universities Educational services na 888 Engineering and architectural SERVICES in c 'not otherwise cleified birth 1870-1889 1890-1909 1910-1929 1930-1949 and geographic location The 1966 labor market area LMA divisions of Connecticut were utilized for the geographic risk analysis Particular attention was given to the LMAS surrounding Connecticut's five largest urban areas and two rapidly expanding previously rural regions A scoring procedure was developed to provide an indica- tor of the duration and severity of occupational asbestos exposure for both cases and controls For each job title in the likely category that could be documented from DCs CDs or both for an individual a score of 2 was assigned A job title from the possible group was given a score of 1 and from the unlikely subset a score of 0 These values were summed across all available time periods for which employment information was available Individuals lacking any employment history which included those never employed and those for whom data were missing were excluded Each of the remaining study subjects was assigned a final single job index of exposure This 751 Journal of Occupational Medicine 25 No. Octob 1983 we. . crude measure provided an ordered exposure variable which was categorized into five levels Level ( included a job index of 0 level 1 included a job index of 1 level 2 a job index of 2 level 3 job indexes of 3 and 4 and level 4 job indexes greater than 4. Each study subject with a job index of exposure was assigned one of the five groups Although the medical records of some cases noted past occupational asbestos exposure this information could not be incorporated into the analysis since such data were lacking for controls and has not been systematically collected for cases over time Haenszel standardized odds ratios were com- puted comparing cases and controls across each of the four levels of exposure to no exposure Finally the Coch- Haenszel Test of Partial Association was applied to test the exposure relationship for trend while controlling for the potential confounding of age which was stratified into year intervals 30 to 49 years 50 to 69 years 70 to 89 years The 90+ stratum with too few numbers to be informative two cases seven controls was excluded from the response analysis These results are reported for an estimated exposure index based on job only The coding of industries into the broad categories of the U.S. Census does not discriminate satisfactorily among jobs with different exposures Controls tended to be older at death with a mean age of 68 years as opposed to 64 for cases Table 4 They predominated in the earlier birth cohorts with 81 born prior to 1910. Since age and year of birth are likely to be related to occupational asbestos exposure as well as to disease status they were considered potential confounders and controlled for in the analysis whenever sample size permitted The confounding effect of these variables however was not substantial The standardized odds ratios differed minimally from the crude and simultaneous adjustment was not deemed necessary The proportions of individuals with at least one job title from DCs CDs or both were comparable for cases and controls and virtually complete using all sources - 98 for cases 99 for controls Table 5 The percentages with 1-4 and 5-8 job titles were nearly identical CDs provided fewer job and industry titles than DCs but more names of specific employers One year prior to death or diagnosis less information was obtained for controls from CDs most likely Table 4 - Demographic Characteristics of Cases and Controls Mean year of death or diagnosis Mean age at death or diagnosis Birth Cohort Distribution % 1870-1889 1870-1889 1870-1889 1890 - 1909 1910-1929 1910-1929 1910-1929 1930 - 1949 Cases 1969 64 8 56 33 3 100 Controls 1966 68 32 49 18 1 100 Males older than 30 years at death or diagnosis born after 1874 attributable to the larger proportion of retirees in the latter group For all other time periods the percentages of cases and controls with a job or industry title were similar Using both CDs and DCs at least one industry title was available for 89 of cases and 90 of controls Results We have described secular and time trends for mesothel ioma in Connecticut from 1935 through 1977 in an earlier report In the present control occupational risk analysis for the years 1955 through 1977 based on job title alone the more than twofold risk for cabinetmakers and carpenters and the nearly fourfold risk for plumbers and pipefitterspipefitters were significant p < .05 Table 6 Excess risk was observed for engineers masons electricians foremen and painters but in none of these categories did it reach statistical significance at the .05 level It should be noted that for the job- and industry analyses the study provided adequate power to detect only large associations for the less common categories of employment Fourteen of the 15 cases among the carpenters were diagnosed as pleural mesothelioma and the single case of periotoneal mesothelioma occurred in the only individual who had worked in a boat yard All seven plumbers and pipefitters were registered at the CTR with pleural mesothelioma and all death certificates reported them to be in this job category Although CD data were available for only four of these cases it was in perfect agreement with DC data and revealed first employment in this category to be at least 30 years before diagnosis for each A parallel comparison of cases and controls using industry title alone revealed a significant association with the rubber industry relative risk RR = 5.08 < .01 Table 7 which was particularly striking when limited to subjects 70 to 89 years of age at death or diagnosis RR = 16.97 p < .005 Three different employers were represented among the five individuals with pleural and one with peri- toneal mesothelioma who had worked at one time in the rubber industry The proportion of cases with possible or likely ex- posure to asbestos on the basis of job title was 67 for the entire state yielding an adjusted RR of 1.63 p < .01 The attributable risk AR in the exposed group was 39 There was little variation in risk across these geo- graphic regions The study provided more than 90 power to detect relative risks of 2 or more at the .05 level for this comparison On the basis of industry title the overall proportion considered to have been exposed was 66 with an RR of 1.36 p < .10 and an AR of 26 Power calculations for this portion of the analysis yielded results similar to those described above Substantial interregional variation was observed in the percent exposed and in the risk for disease One large industrialized region LMA1 exhibited nearly a four risk p = .02 One employer in LMAI accounted for three times as many cases sixas controls two with an unadjusted RR of 9.83 All the cases from LMAS the exception of one with industry unknown had worked at one time in an industry judged to be associated with probable or possible exposure Histologic review of all male cases from LMAI an area in which an asbestos plant is located and LMAS an area in 752 Mesothelioma in Connecticut et al Table 5 Completeness of Occupational Data for Cases and Controls From Death Certificates and City Directories Source -- CD ; 1 yr prior to Dx 10 yr prior to Dx 20 yr priotro Ox 25 yr prior to Ox 30 yr prior to Dx 40 yr prior to Dx 50 yr prior to Ox DC and CD 1-4 job titles 5-8 job titles % with Job Title Cases Controls 92 96 76 69 46 26 53 42 46 45 41 39 30 35 26 24 10 18 98 99 71 72 27 27 % With Industry Title Cases Controls 73 85 69 67 45 23 43 40 39 45 36 39 30 36 19 23 8 14 89 94 % With Employer Name Cases Controls 591 71 47 45 40 34 31 19 3 NCS 41 53 17 28 29 27 25 15 8 NC . Uninformative titles such as retired student excluded t When seven cases in living persons excluded from the denominator percentages become 96 76 62 # Cases less than 20 years of age at search year excluded from denominator NC indicates not calculated || Total number of jobs for cases = 475 3.23 for controls = 1,412 control which shipyards are located resulted in reclassification of two % and one 17 respectively as not mesothelioma or probably not mesothelioma There was no observable indication of diagnostic bias positives in these regions where knowledge of an exposure hazard was available in the medical community Using exposure either through job or industry as a criterion the statewide proportion of cases with an indicator of occupational exposure was 85 yielding an age- adjusted RR of 1.57 p < .05 and an AR of 36 In an examination of a birth cohort effect all indi- viduals except those born between 1930 and 1949 were more likely than controls to have been exposed to asbestos Table 6 - RR of Mesothelioma Associated With Selected Job Categories Job Title 95 Confidence RR Interval N Engineers Brickmasons and stonemasons Cabinetmakers and carpenters Electricians Foremen Painters construction and maintenance Plumbers and pipefitters 2.72 2.15 2.25 1.29 1.57 1.39 3.87 .85 8.68 .37,12.50 .37,12.50 1.13 4.48 .39 4.24 .84 2.94 .52 3.71 11 5 9 35 14 50 20 1.38 10.82 13 N indicates the number of male cases and controls older than 30 years at death or diagnosis born after 1874 who ever worked in the category total N for each independently calculated t .05 RR was 611 147 cases 464 controls on the basis of their job title The differences were statistically significant RR = 2.16 p < .02 for the 1910-1929 cohort only The overall adjusted 1870-1889 18901909 1910-1929 1930-1949 RR was 1.69 p < .01 Utilizing the job exposure score as previously defined a monotonic increase in risk associated with higher levels of estimated asbestos exposure was suggested particularly for the oldest age group Table 8 There was a slight increase Table 7 - RR of Mesothelioma Associated With Selected Industry Categories Industry Title RR 95 Confidence Interval N> Construction Miscellaneous nonmetallic mineral and stone products Electrical machinery equipment and supplies Aircraft and parts Shipbuilding and boat building Yarn thread and fabric mills Rubber product Automobile repair and related service 1.21 .60 2.45 45 1.64 .15 18.06 3 2.79 1.03 .86 6.67 22 .43 2.49 25 1.09 .35 3.42 16 .57 .17 1.92 20 5.08t 16.11 10 .65 .08 5.53 6 N indicates number of male cases and controls older than 30 years at death or diagnosis born after 1874 who ever worked in the category total N for each independently calculated RR was 611 147 cases 464 controls t < .01 Journal of Occupational Medicine 25 No. October 1983 753 Table 8 - RR of Mesothelioma Associated With Level of Occupational Asbestos Exposure by Age De ee eee Age Group Level of Occupational Asbestos Exposure bk 0 . _ 1 2 3 4 xfor N Trend 30-49 50-69 70-89 All ages 1.00 1.00 1.00 1.00 .47 1.11 1.59 2.19 1.78 1.19 1.34 1.17 1.60 4.59 2.20 .t 1.67 5.35 2.73 66 257 272 611 NS NS .0001 .0005 * Level 3 is exposure scores 3 or 4 t Level 4 is exposure scores 5 to 16 # RR could not be calculated due to 0 denominator one case 0 controls with exposure < .001 11 adjusted relative risks 1 < .005 for the 30 to year group but numbers were small and the variances of the RR estimates were large There was a sizeable number of cases 80 and controls 177 in the 50- to year group and a fairly constant risk associated with increasing estimated exposure was indicated Those males 70 years or older n = 272 with job exposure scores in levels 3 and 4 exhibited highly significant relative risks for this disease The ARs for those exposed in these two levels were 78 and 81 respectively The test for trend that compared the relative proportions of cases and controls across increasing levels of estimated asbestos exposure while controlling for age was highly significant overall p < .0005 and for the 70 to year age group p < .0001 Discussion The major difficulties encountered in a noninterview retrospective study of an mesothelioma association relate to the inadequacy of occupational histories the potential for misclassification of exposure status and errors in diagnosis Although partial employment data were obtained for nearly all study subjects complete work histories were available for very few and information regarding parttime work or hobbies was completely absent The level of completeness varied geographically with the less mobile industrialized regions having more complete CD coverage than the more rural less populated areas Completeness by geographic region did not differ however between cases and controls For the seven cases in living persons occupational information could be obtained from CDs only When the analyses were repeated excluding these individuals however the findings were unchanged These occupational history limitations were balanced in part by the advantage that respondent memory bias and faulty interviewing tech- niques associated with widely publicized carcinogenic. hazards such as asbestos were avoided in this noninterview approach Although the inability to reconstruct dust measurements prevented direct examination of a response relationship the job exposure index a correlate of asbestos exposure demonstrated increasing disease risk with higher 754 scores particularly for the 70 to year age group An attempt was made to test the possibility of a systematic inflation of case scores due to more complete occupational information for the diseased population Job title availability for the maximum of eight time periods searched was comparable for both groups Table 5 with 71 of cases and 72 of controls having 1-4 job titles and 27 of each having 5-8 job titles In addition the stratified relative risk calculations made adjustment for the large proportion of retirees in the control group with fewer job titles one year prior to death The elevated risks associated with the older age group and with the 1910-1929 birth cohort are consistent with the poor dust control measures in most workplaces prevalent in earlier years Peto et 17 in their review of a number of studies showed a wide variation in the peritoneal ratio among exposed persons We have determined this ratio in our cases and attempted to relate it to some param eters that seem to influence its distribution An analysis of proportions of cases of mesothelioma by site within each of three age groups 30 to 49 years 50 to 69 years and 70 to 89 years for each sex separately showed that among men the proportions of pleural disease increased as age increased while the proportions of peritoneal disease decreased Pleural mesothelioma accounted for 79 of cases aged 50 to 69 years and 93 of cases aged 70 to 89 years at diagnosis Job AR in the exposed was about 80 for these older men Results Table 6 for carpenters and cabinetmakers 14 of 15 pleural and plumbers and pipefitters seven of seven pleural are consistent with the above proportions and with Table 8 in suggesting that pleural mesothelioma in men over 50 in Connecticut is highly likely to have been associated with and probably caused by exposure to asbestos at work These data also indicate that occupational exposure to asbestos probably explains most of the disease in these older men and that it began in the 1930s Peto et al17 showed that mesothelioma death rates were independent of age at first exposure and it may therefore be assumed that age in itself has no direct influence These authors did show a strong correlation between discase and length of time since first exposure The fact that the inci- dence of mesothelioma of the pleura increases sharply in the males in the older age groups with the higher ex posure scores in our cases is consistent with the long latency known to be associated with this disease This is also in conformity with Peto et al's findings The potential for random misclassification of exposure status based on subjective blind review oflimited work histories restricts our ability to draw firm conclusions because such errors produce attenuation toward an RR of 1 This is particularly relevant with regard to the true proportion occupationally exposed and the true magnitude of the RR which is likely to be higher than our findings indicate Blind subjective review has also been used by other investigators in estimating exposure but most often in conjunction with interview data 18,19 It is widely held that relatively low exposure levels 20 to 50 years prior to diagnosis may lead to the development of mesothelioma The cases described with no known ex- posure may fall into this category may have been exposed from the general environment or may be related to some Mesothelioma in Connecticut et al PF. other unknown etiologic factor Careful examination of the mention of this disease was made on eith ' an certifi occupational data for these cases and the controls with no known exposure did not reveal any unusual differences cate The third person a male who was employ 'uduring the period 1921 to 1932 was not included in McDonald There were no geographical associations of peritoneal and Fry's cohort which was defined as persons employed mesothelioma with asbestos cement pipe used in Connecti- in the period 1937 to 1959 only These three cases repre- cut in a search made by one of us J.W.M. in a report to sented only small proportions one of 30 males two of 12 the Environmental Protection Agency females with mesothelioma in the LMA that included the The possibility of misdiagnosis is important Dr. Raymond Yesner chairman of the World Health Organization plant making asbestos products Most of the remaining male cases had occupational history indicators of asbestos expo- Committee on Nomenclature of Lung Cancer and one of sure at work us J.W.M. recently reviewed 964 randomly sampled autopsy cases reported to the CTR as primary lung cancer during the 45 years from 1935 through 1979. One of these was diagnosed as a mesothelioma The five cases of mesothelioma in the present study identified from VA hospital There was no support for the hypothesis of a significant residential risk to persons living in the vicinity of this plant The original control proportions among those residing in LMAI at time of death or diagnosis were 20 and 12 for males and 17 and % for females respec- autopsies included two 1963 cases in which the initial diagnosis had been lung cancer This suggests that in the past as many as one or two per thousand cases diagnosed as lung cancers may have been mesotheliomas but the proportion is probably smaller at present because of increased awareness by clinicians and pathologists The association with the rubber industry requires addi- tively After excluding all males with possible or likely occupational asbestos exposure based on job title or industry title or both there remained 9.5 of all male cases and 9.2 of all male controls in that LMA No real residential difference was observed for either males or fe- males This result may be related to the asbestos fiber type used at the plant which McDonald and Fry reported to tional exploration because of the lack of specific informa- have been the less hazardous chrysotile and would there- tion regarding the many aspects of manufacturing processes fore not be extrapolated to all asbestos products manu- lumped into this broad category and the potential for chance association due to the examination of multiple facturers One of the female cases an employee who worked at the comparisons McDonald reported three cases and one control who were employed by a factory making rubber asbestos friction materials plant may have had domestic exposure from her husband who also worked there for products in her North American survey of mesothelioma These were selected from all male cases 150 and their many years We explored this general issue by reviewing cancer incidence among 193 spouses the majority of whom matched controls who did not work in occupations asso- were female Twenty case spouses have been reported ciated with likely asbestos exposure Exposure to rubber among all 344 control matched pairs in her survey did not reveal an elevated RR The association was in fact in to the CTR 1935-1978 with a confirmed malignancy There are no reported tumors of the pleura lung peri- toneum or ovary in the spouse group This provided no the opposite direction RR = 0.6 _- The manufacture of containing friction materi- als was associated with job histories in only three cases in the present study First hire was in the 1920s and 1930s with time intervals of about 30 years before mesothelioma indication of domestic risk However since there were no control spouses inferences involving domestic exposure were very limited Only two persons possible case of with probable cases and one with a mesothelioma were known to have was diagnosed Slide review confirmed a diagnosis of peritoneal mesothelioma in a female clerical worker case ) worked in shipbuilding or repair The LMA that included these industries showed no excess proportion of cases over with approximately 30 years employinent In this indi- vidual asbestosis was also considered to be present Similar- ly in a male employee case 2 with the same surname a diagnosis of possibly pleural mesothelioma was made These two individuals were discovered to be brother and sister Their common relative the husband of case 1 and brother of case 2 was employed by the same asbestos company for a period of at least 30 years and died at age 56 controls Selikoff oral communication 1978 has suggested that heavy asbestos exposures occurred in the late 1940s and that cases might develop in the 1970s and later The two probable cases with recorded shipbuilding ment in the present study were diagnosed 1975 and 1976 which is consistent The findings of Peto et 21 how ever indicate that the consequences of wartime exposure may have been exaggerated Future data from Connecticut years of an acute coronary thrombosis He resided consecu- should clarify this question tively with his brother for at least 17 years and with his i wife for over 15 years prior to his death The third case from the same plant that of a female clerical worker who had been employed there less than five years was classified Conclusion Difficulties in ascertaining occupational asbestos exposure histories in our study population indicate a need for as probably pleural mesothelioma In a search of city better recordkeeping in industry medical institutions and directories by single years no other employment was found , for this woman tumor registries Our methodology utilizing indirect means of ascertainment has enabled us to estimate the extent to Two of the three cases in employees at the asbestos which occupation or industry may affect the incidence of plant were included by McDonald and Fry recently reported cohort study which was based certificate information and employee records The of mesothelioma however was not ascertained in their on death diagnosis since no mesothelioma among males in Connecticut related or industry factors appear to account for a large per- centage of all mesothelioma cases in males diagnosed in the State between 1955 and 1977. Lack of detailed informa- Journal of Occupational Medicine 25 No. October 1983 755 other unknown etiologic factor Careful examination of the mention of this disease was made on either an certifi- occupational data for these cases and the controls with no cate The third person a male who was employ 'uduring known exposure did not reveal any unusual differences the period 1921 to 1932 was not included in McDonald There were no geographical associations of peritoneal and Fry's cohort which was defined as persons employed mesothelioma with asbestos cement pipe used in Connecti- in the period 1937 to 1959 only These three cases repre- cut in a search made by one of us J.W.M. in a report to sented only small proportions one of 30 males two of 12 the Environmental Protection Agency females with mesothelioma in the LMA that included the The possibility of misdiagnosis is important Dr. Ray plant making asbestos products Most of the remaining male mond Yesner chairman of the World Health Organization cases had occupational history indicators of asbestos expo- Committee on Nomenclature of Lung Cancer and one of sure at work us J.W.M. recently reviewed 964 randomly sampled autopsy cases reported to the CTR as primary lung cancer There was no support for the hypothesis of a significant residential risk to persons living in the vicinity of this during the 45 years from 1935 through 1979. One of these plant The original control proportions among those was diagnosed as a mesothelioma The five cases of meso- residing in LMAI at time of death or diagnosis were 20 thelioma in the present study identified from VA hospital and 12 for males and 17 and 18 for females respec- autopsies included two 1963 cases in which the initial tively After excluding all males with possible or likely diagnosis had been lung cancer This suggests that in the occupational asbestos exposure based on job title or past as many as one or two per thousand cases diagnosed as industry title or both there remained 9.5 of all male lung cancers may have been mesotheliomas but the propor- cases and 9.2 of all male controls in that LMA No real tion is probably smaller at present because of increased residential difference was observed for either males or fe- awareness by clinicians and pathologists males This result may be related to the asbestos fiber type The association with the rubber industry requires addi- used at the plant which McDonald and Fry reported to tional exploration because of the lack of specific informa- have been the less hazardous chrysotile and would there- tion regarding the many aspects of manufacturing processes fore not be extrapolated to all asbestos products manu- lumped into this broad category and the potential for facturers chance association due to the examination of multiple One of the female cases an employee who worked at the comparisons McDonald reported three cases and one asbestos friction materials plant may have had domestic control who were employed by a factory making rubber exposure from her husband who also worked there for products in her North American survey of mesothelioma many years We explored this general issue by reviewing These were selected from all male cases 150 and their cancer incidence among 193 spouses the majority of whom matched controls who did not work in occupations asso- were female Twenty case spouses have been reported ciated with likely asbestos exposure Exposure to rubber to the CTR 1935-1978 with a confirmed malignancy among all 344 control matched pairs in her survey did There are no reported tumors of the pleura lung peri- not reveal an elevated RR The association was in fact in toneum or ovary in the spouse group This provided no the opposite direction RR = 0.6 indication of domestic risk However since there were no The manufacture of containing friction materi- control spouses inferences involving domestic exposure als was associated with job histories in only three cases in were very limited the present study First hire was in the 1920s and 1930s Only two persons with probable cases and one with a with time intervals of about 30 years before mesothelioma possible case of mesothelioma were known to have was diagnosed Slide review confirmed a diagnosis of peritoneal mesothelioma in a female clerical worker case ) worked in shipbuilding or repair The LMA that included these industries showed no excess proportion of cases over with approximately 30 years employinent In this indi- vidual asbestosis was also considered to be present Similar- ly in a male employee case 2 with the same surname a controls Selikoff oral communication 1978 has suggested that heavy asbestos exposures occurred in the late 1940s and that cases might develop in the 1970s and later The diagnosis of possibly pleural mesothelioma was made These two individuals were discovered to be brother and shipbuilding two probable cases with recorded ment in the present study were diagnosed 1975 and sister Their common relative the husband of case 1 and brother of case 2 was employed by the same asbestos company for a period of at least 30 years and died at age 56 years of an acute coronary thrombosis He resided consecu- 1976 which is consistent The findings of Peto et 21 how- ever indicate that the consequences of wartime exposure may have been exaggerated Future data from Connecticut should clarity this question on tively with his brother for at least 17 years and with his wife for over 15 years prior to his death The third case Conclusion from the same plant that of a female clerical worker who Difficulties in ascertaining occupational asbestos expo- 2 had been employed there less than five years was classified sure histories in our study population indicate a need for as probably pleural mesothelioma In a search of city better recordkeeping in industry medical institutions and directories by single years no other employment was found , for this woman tumor registries Our methodology utilizing indirect means of ascertainment has enabled us to estimate the extent to J Two of the three cases in employees at the asbestos which occupation or industry may affect the incidence of plant were included by McDonald and Fry in their recently reported cohort study which was based on death certificate information and employee records The diagnosis of mesothelioma however was not ascertained since no mesothelioma among males in Connecticut related or industry factors appear to account for a large per- centage of all mesothelioma cases in males diagnosed in the State between 1955 and 1977. Lack of detailed informa- Journal of Occupational Medicine 25 No. October 1983 755 - number occupationally exposed The large proportion of cases of older men with some indication of occupational .. exposure the increase over time in the female ratio . and the lack of difference between the proportion of cases and controls without evidence of occupational exposure residing in the LMA containing an asbestos plant do not provide support for the view that ambient air concentrations were a major factor in influencing the observed increment in cases of mesothelioma during the course of the study period The reduction of unnecessary exposure to asbestos in the workplace remains the highest public health priority Future studies of the mesothelioma cases recorded in the CTR should endeavor to clarify the clusters of cases in the rubber manufacturing industry and in the plant located in LMA where an RR of nearly 10 was observed Collab- oration the Industry or industries concerned will be sought to explore the implications of these results This will be attempted in conjunction with continuing surveillance of mesothelioma in Connecticut . Acknowledgments Lawrence Hally Regina Robinson and Marianne Delpo of the Connecticut Cancer Epidemiology Unit and Nora Naughton of the CTR provided technical assistance References 1. Lewinsohn HC Meigs JW Teta MJ et al The influence of occupational and environmental asbestos exposure on the incidence of malignant mesothelioma in Connecticut in Wagner JC Ed Biological Effects of Mineral Fibres Lyon France IARC Publications No. 30 vol 2 1980 pp 655-660 2. Bruckman L Rubino RA Christine B Asbestos and mesothelioma incidence in Connecticut APCA / 121-126 1977 3. Bruckman L A study of airborne asbestos fibers in Connecticut in Gravatt GC LaFleur PD Heinreichf KFJ Eds Workshop on Asbestos Definitions and Measurement Methods Washington D.C National Bureau of Standards Special Publication 506 1978 pp 179-190 4. 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Milne JEH Thirty cases of mesothelioma in Victoria Australia A retrospective survey related to occupational asbestos exposure BrJ Ind Med 115-122 1976 19. McDonald AD Malignant Mesothelioma in North America Cancer 1650-1656 1980 20. McDonald AD Fry IS Mesothelioma and fibre type in three American asbestos factories - Preliminary report Scand J Work Environ Health 53-58 1982 21. Peto J Henderson BE Pike MC Trends in mesothelioma incidence and the forecast epidemic due to asbestos exposure during World War II in Peto R Schneiderman M Eds Banbury Report 9 Quantification of Occupational Cancer Cold Springs Harbor Cold Springs Harbor Laboratory 1981 pp 51-72 756 Mesothelioma in Connecticut et al