Document Ne7oRrwj4mrowQwbX5012kzYE

Reprinted from: BIOLOGICAL EFFECTS OF MINERAL FIBRES. Vol. 2 J. C. WAGNER Lyon, (lARC Scientific Publications bio 30) 1980 PLAINTIFF'S EXHIBIT THE INFLUENCE OF OCCUPATIONAL AND ENVIRONMENTAL ASBESTOS EXPOSURE ON THE INCIDENCE OF MALIGNANT MESOTHELIOMA IN CONNECTICUT H.C. LEWINSOHN Raybestos-Marihattan, Ins., Trumbull, CN, USA J.W. MEIGS & M.J. TETA Connecticut Canaer Epidemiology Unit, Yale School of Epidemiology and Public Health, New Haven, CN, USA J.T. FLANNERY Connecticut Tumor Registry, Connecticut State Department of Health, Hartford, CN, USA INTRODUCTION The combined sex age-adjusted mesothelioma incidence rate for Connecticut was reported recently to have increased ten-fold since 1935. Although available statistics might be subject to diagnostic error, the apparent rise was attributed to the increase in the state's 'cumulative asbestos consumption'. Complete occupational histories for the 133 cases of mesothelioma were not presented. An ambient air standard of 30 ng/m3 measured over a 30-day interval was proposed and was justified by the reported rise in the state's mesothelioma incidence (Bruckman, 1978). In the present study, the cases of mesothelioma recorded in the Connecticut Tumor Registry (CTR) were re-examined to determine the role of occupational and environmental exposures and to consider possible diagnostic errors through review of available histological material. -655- -> J CTC008914 UCC 017787 656 LEWINSOHN ET AL. MATERIAL AND METHODS The 229 cases of malignant mesothelioma identified by the CTR occurred at the following sites: pleura (147), peritoneum (33) and other sites (49); pleural tumours other than mesotheliomas were also recorded (38) (Table 1). Medical, demographic and occupational data were collected for the cases and for their respective spouses from hospital records, death certificates and City Directories (The Price and Lee Company, 1890-1977). Similar information was gathered for a random sample of decedents in Connecticut aged 20 to 98 years. The 1970 US Census Industrial and Occupational Codes (US Department of Commerce, Bureau of the Census, 1971) were assigned to the employment information obtained. Those cases with occupations associated in the literature with malignant mesothelioma were selected for study from all those with occupations in which there was probable asbestos exposure (Hutchison, 1976; Levine, 1978; McDonald, 1979; Weston, 1976). Table 1. Sex, age and diagnostic characteristics of cases of malignant mesothelioma and other pleural tumours diagnosed in Connecticut, 1935-1977 Diagnosis^ Pleural mesothelioma Pleural tumour (other than mesothelioma) Peritoneal mesothelioma Mesothelioma at other sites & at unknown sites Total Males Females Total Mean age Percent 'positive^ histology Percent autopsied* 102 W)d 24 02) 45 (37) 14 (8) 147 (131) 38 (20) 61 (62) 62 (63) 93 (95) 71 (85) 40 (38) 35 (37) 20 08) 13 01) 33 (29) 58 (59) 94 (97) 29 (21) 175 045) 20 (14) 92 (70) 49 (35) 267 (215) 52 (54) 59 (60) 84 (86) 88 (93) 89 (88) 33 (41) 44 (45) a World Health Organization (1976) b SEER, 1976 Code/Field Number 19 (US Department of Health, Education, and Welfare, National Cancer Institute, 1976) (No. autopsied/no. deceased) x 100 d Numbers in brackets refer to the period 1955-1977 Descriptive epidemiology for this research pertains to the time interval 1935-1977. Case-control comparison and statistical modelling include 215 cases diagnosed after 1954 and 605 controls (1955-1977). Information from 1935-1954 was inadequate for such comparisons due to limited occupational and clinical data and to the lack of awareness of mesothelioma. ~4~*J d Zf-z 4 CTC008915 UCC 017788 MALIGNANT MESOTHELIOMA IN CONNECTICUT 657 RESULTS The crude incidence rate for mesothelioma in Connecticut is 2.2/ million for the years 1935-1977. Age-adjusted incidence rates per 100,000 population (using the 1950 US population as a standard) increased for both sexes, but there was a rapid rise from about 1960 for males (Fig. 1). Of the 229 cases, 195 were reported after 1954. The mean age at diagnosis was 59 years. The geographic distribution of these cases reveals a clustering in dense urban areas. Ten cases were reported (1955-1977) in an area where shipyards are located, and five of these were identified between 1975 and 1977. FIG. 1. AGE-ADJUSTED INCIDENCE RATES OF MESOTHELIOMA IN CONNECTICUT BY YEAR OF DIAGNOSIS AND SEX 060 HI male 0.50 female SR both 0.40 o o o oo \ 0.30 _ CcD 0.20 - tftAaio _ v 19351941 1942 1947 19481953 A logistic regression model was fitted to examine the incidence of pleural mesothelioma (1955-1977) as a function of time, age and sex. Connecticut population figures were used for denominator data in the A-U23'2 I, CTC008916 UCC 017789 658 LEWINSOHN ET AL. estimate of disease probability. The main effects model provided a reasonably good fit (P > 0.10). Relative risks (here approximated by the odds ratio) over time intervals, age categories and sex groups were estimated. Persons alive in 1975-1977 had a 3.5 times greater risk of developing pleural mesothelioma than those alive between 1955 and 1964 (95% confidence intervals (Cl): 2.25, 5.48). With progression across the age intervals 45-54, 55-64, 65-74..., the individual risk of this disease is 1.5 times greater than in the preceding ten-year age group (95% Cl: 1.13, 1.31). Males have 3.0 times the risk of females (95% Cl: 2.10, 4.22). These descriptive and analytical results assume completeness and accuracy of case identification. A sizeable proportion (56%) of the 267 cases were not autopsied; and autopsy percentages for pleural tumours other than mesothelioma and for mesotheliomas at other or unknown sites are low - 35% and 33%, respectively. The unknown site, group had a mean age of only 52 years (Table 1). The differentiation of cases of malignant pleural tumours into mesothelioma and other pleural tumours is suspect. A discriminant function analysis of these two groups of cases (diagnosed after 1954) on the basis of age, sex, survival time, stage and number of tumours yields a 60% misclassification. These results suggest possible misdiagnosis and the advisability of a case review, which is made feasible by the large proportion of patients diagnosed on the basis of available histological material (Table 1). When the mesothelioma incidence has been adjusted for diagnostic weaknesses and misclassifications and when the occupationally exposed cases, controls and spouses have been identified, it may be possible to determine the role of environmental asbestos exposure, if any, in the remaining cases. SUMMARY Medical, occupational and demographic data were collected for 229 cases of malignant mesothelioma and 38 other pleural tumours, their spouses, and 605 controls. Methods were developed for classifying subjects into probable asbestos exposure categories. Although disease incidence rates exhibited a rapid increase from 1955 to 1977, there remains a serious question of diagnostic reliability. A case review is being undertaken. AU2326 UCC 017790 CTC008917 MALIGNANT MESOTHELIOMA IN CONNECTICUT 659 RESUME Les auteurs ont recueilli des donnees medicales, professionnelles et demographiques sur 229 sujets atteints de mesotheliome malin et 38 d'autres tumeurs pleurales, leurs conjoints et 605 temoins. Ils ont mis au point des methodes permettant de classer les individus en cate gories d'exposition probable a l'amiante. Bien que les taux d'inci dence de la maladie accusent une rapide augmentation de 1955 a 1977, il subsiste un serieux probleme de fiabilite diagnostique. Une etude de cas individuels est presentement entreprise. ACKra^UEDGEMENTS The authors wish to acknowledge the technical assistance of Linda Ziter Mowad, R.N. of the Connecticut Cancer Epidemiology Unit and of Kathleen Pinto of Raybestos-Manhattan, Inc. This investigation was supported by grants number N01 CP 33235 and N01 CP 61002 awarded by the National Cancer Institute, DHEW, and by the Institute of Occupational Medicine and Hygiene, Yale University School of Medicine. REFERENCES Bruckman, L. (1978) A study of airborne asbestos fibers in Connecticut. In: Gravatt, G.C., LaFleur, P.D. & Heinreich, K.F.J., eds, Workshop on Asbestos: Definitions and Measurement Methods (National Bureau of Standards Special Publication S06), Washington DC, National Measurements Laboratory, pp. 179-190 Hutchison, M.K. (1976) A Guide to the Work-Relatedness of Disease, Washington DC, US Department of Health, Education, and Welfare, US Government Printing Office C T C 0 0 8 9 18 UCC 017791 660 LEWINSOHN ET AL. Levine, R.J., ed. (1978) Asbestos: An Information Source (DHEW Publi cation Number (NIH) 79-1681), Washington DC, US Department of Health, Education, and Welfare McDonald, A.D. (1979) Mesothelioma registries in identifying asbestos hazards. Ann. N.Y. Acad. Soi., 330, 441-454 The Price and Lee Company (1890-1977) New Haven, CN Price and Lee City Directory, US Department of Commerce, Bureau of the Census (1971) 1970 Census of the Population. Alphabetical Index of Industries and Occupations, Washington DC, US Government Printing Office US Department of Health, Education, and Welfare, National Cancer Institute (1976) Cancer Surveillance Epidemiology and End Results Reporting, SEER Program, Washington DC, US Government Printing Office Weston, R.F. (1976) Technical Feasibility and Economic Impact of OSHA Proposed Revision to the Asbestos Standard, prepared for the Asbestos Information Association/North America, Washington DC, Fig. 2-1, p. 2-3 World Health Organization (1976) ICD-0 International Classification of Diseases for Oncology, Geneva CTC008919 *02328 UCC 017792