Document ymB0k7nOgLOjgXm52gkLpZgb2

Scand J Work Environ Health 2000;26(2): 112--117 Incidence rates of malignant mesothelioma in Denmark and predicted future number of cases among men by Jesper Kjaergaard, MD,1 Michael Andersson, DrMedSc1 Kjaergaard J, Andersson M. Incidence rates of malignant mesothelioma in Denmark and predicted future number erf casesamong men. Scand J Work Environ Heafth 1999;26(2):112--117. Objectives This study analyzed the incidence rates of malignant mesothelioma in Denmark in order to predict the future number of cases that wfl] occur among Danish men. Methods The 1912 cases ofmalignant mesotbeliomaieported to the Danish Cancerregistry in 1943--1993 were analyzed in order to describecurrent incidence rates. By a Poisson regression model therelative risks ofsynthetic birth cohorts were estimated and used in the prediction of the future number ofcases that will occur among Danish men. Results The incidencerate increased to 1.33 per 100 000 person-years in 1983--1987 among men and to 0.51 in 1973--1977 among women. From the Poisson regression model, the risk for birth cohorts of men, relative to the 1940--1944 cohort, peaked in the 1940--1944 cohort and decreased to 057 in the 1950--1954 cohort The age- specific incidence rare peaked at 246 per 100 000 person-years in the age group 80--84 years. The future annual number ofmesothelioma cases is expected to peak around 2015 with 93 cases among men bom before 1955. Conclusions The fit ofthe models was not ideal, but with careful interpretation of the results, it was concluded that a further increase in the number of mesothelioma cases can be expected, and the effect of regulating the environmental exposure to asbestos cannotbe expected within the next 10--15 years. Key terms age-cohortmodel, epidemiology. About 65 cases of malignant mesothelioma are reported in Denmark annually (1). This rare cancer is strongly as sociated with exposure to asbestos (2,3). Hence the use of asbestos in the Danish industry was banned with few exceptions in 1979 (4,5). It is estimated that more than half the mesothelioma cases are caused by asbestos (6). Asbestos fibers are used in industry, in Denmark mostly in shipyards, for insulating materials, pipe fittings, and brake linings for trains and automobiles (3). Although the carcinogenicity of especially the amphibolc asbestos fib ers has been known since the 1960s, the use of asbestos in industry was continued for several years, up until the legislation prohibiting it. The effect of banning industrial asbestos use has not yet appeared in the published incidence rates from the registry (7), perhaps due to the latency of 30 years or more from exposure to diagnosis of the disease (8,9). The Danish Cancer Registry was founded in 1943 and collects detailed information on diagnosed cancer cases (10). Recent publications have predicted an alarming in crease in mesothelioma deaths over the next 30 years by statistical modeling (11--13). In the present study, we aim to demonstrate an effect of the decreased exposure level through a log-linear regression analysis of the birth cohort and the period of diagnosis for Danish men, with a prediction of incidence until the year 2040. The meth ods of the analysis are comparable with those used in re cent studies of mesothelioma trends (11--14). Materials and methods Data from the Danish Cancer Register were used in the study. The completeness and accuracy of the register is considered to be high (1,10). All cases of malignant mesothelioma diagnosed and coded as such in the period 1943--1993 were identified according to the modified ICD-7 classification (pleura, 1 Institute of Cancer Epidemiology, Danish Cancer Registry, Danish Cancer Society, Copenhagen, Denmark, Reprint requests to: Dr Jesper Kjsrgaatd, Institute of Cancer Epidemiology, Danish Cancer Registry', Danish Cancer Society, Strandboulcvarden 49, DK-2100 Copenhagen 0, Denmark. [E-mail: jesperk cancer.dk] 112 Scand J Work Environ Health 2000, vo! 25, no 2 peritoneum and pericardium) in use prior to 1978 by the International Classification of Diseases (ICD) (1,15) and afterwards according to the ICD-0 (16) through a com bination of the morphological and topographical codes. Four cases recorded as mesothelioma of the scrotum were excluded. For each case gender, date of birth, month and year of diagnosis, and the ICD-7 or ICD-0 codes were ex tracted and cases with ICD-0 codes were converted to ICD-7 codes by a computerized conversion program into the locations pleura, peritoneum or pericardium. For cal culating the incidence rates, the age distribution in the Danish population was determined through the aid of Sta tistics Denmark (17). Incidence rates directly standard ized according to the World Standard Population (WSTP) (18) and the 95% confidence intervals (95% Cl) were cal culated on the assumption of a Poisson distribution of the observed cases (19). The distribution of malignant mesothelioma among men by age and year of birth was analyzed by Poisson regression, as done by Peto and his co-workers (14). Birth cohorts were computed as synthetic cohorts according to age and date at diagnosis, each case being assigned to 1 birth cohort. Person-years at risk (PYR) were construct ed in a similar way. Age-specific incidence rates, k,, were estimated for the age groups 30--34 years (a=l) to 85-- 89 years (a=12). Birth-cohort-specific relative risks, cb, ' were calculated for the cohorts bom in 1875--1879 (b=l) to 1950--1954 (b=16). The relative risk for the 1940-- 1944 cohort, el(, was set at unity. The predicted annual age-specific incidence rates were calculated as the product of the age-specific rate and the relative risk of the birth cohort, k, cb. The fitted numbers of cases were calculated as the product of the predicted age-specific incidence rates and the personyears in the cell. Goodness-of-fit was evaluated by the Pearson's x5-test, and the P-values of the fit were com puted (20, 21). The predicted rates were used to estimate the number of future mesothelioma cases. The estimate was made for men bom before 1955 and for all men, assuming that the relative risk for cohorts bom after 1955 was 50% of the 1940--1944 cohort. This approach was used due to the very few observed cases in the younger birth cohort, since the lack of cases made the risk estimates unreliable. Pop ulation prognoses of Statistics Denmark (17) were used for calculating the estimated number of cases..The as bestos consumption in Denmark was used for estimating the exposure to asbestos (22). For comparison a similar analysis was done using the variables period of diagnosis and age at diagnosis. The age groups were the same, and the periods, p^, were c=l for 1943--1947, to c=l0 for the period 1988--1992. The last period (p;l) only contained data from 1993. The period 1988--1992 (pl0) was used as the basis for comparison because most of the cases were diagnosed during this period. Results In table 1 the total number of cases of malignant mes othelioma is shown according to their location among the men and women. The proportion of pleural mesothelio mas was greater for the men (89.5%) than the women (71.3%), and the proportion of the peritoneal tumors was greater among the women than among- the men. Tumors of the pericardium comprised less than 2% of the total for both genders. The incidence rate for the men was higher than that of the women, and it increased from 0.10 per 100 000 person-years in 1943--1947 to 1.32 (95% Cl 0.47-- 2.17) per 100 000 person-years in 1983--1987, and then decreased to 1.31 (0.46--2.15) per 100 000 person-years in 1988--1992 (figure 1). The incidence rate for the women increased to 0.51 per 100 000 in 1973--1977, and then decreased to 0.27 in 1988--1992. Table 2 shows the age- and binh-cohort-specific ob served number (fitted number below) of cases of malig nant mesothelioma among the men. Under the birth-co hort intervals the estimated birth-cohort-specific relative risks are shown, rising to a maximum (1.00) in the co hort bom in 1940--1944. The estimated age-specific rates are shown under the corresponding age interval. The rate is 0.66 per 100 000 person-years in the age group 30--34 years, and it increases steadily to 246 per 100 000 .person-years in the group 80--84 years. As an evalua tion of the goodness-of-fit, the difference between the ob served and the fitted number of cases was computed by Pearson's y:-iest (x2=109, df=92, P=0.11). Figure 2 shows the annual observed number of cases of malignant mesothelioma in quinquennia defined by midyear. Note that the period 1993--1997 only contains data of the year 1993. The estimated annual number of cases is shown for comparison, and this graph is extend ed into the predicted annual numbers of cases in the years Table 1. Number of cases of malignant mesothelioma in Den mark in 1943--1993. (ICD = International Classification of Dis eases) Site of tumor Men Women N %N % Pleura Peritoneum Pericardium Total 1200 123' IS 1341 89.5 ' 9.1 1.3 100 407 154 ID 571 71.3 27.0 1.8 100 1 Inciuaing one tumor coded as the iCD-7th revision code 199.3; unspecified site, abdomen. Scand J Work Environ Health 2000. voi 26. no 2 113 A' *r+-- Annual incidence rate per 100 000 person-years Year Denmark in 1943--1993. Table Z. Cases of malionanl mesothelioma among Danish men in 1943--1993 and the fitted numbers based on the birth cohort analysis. Each cell shows the observed (0) number of mesothelioma cases next to the fitted (F) number derived from the birth cohort model by multiplying the population person-years (not shown) by the product of k, and c,,. Birth cohort, c,,, Is defined by midyear. Year of birth Relative Afle group (years)1 3D--34 35--39 40-44 45--49 50--54 . 55--59 60-64 65--69 70--74 75--7S 80--84 85--89 (0.66) (2.22) (4.18) (7.76) (19.7) (30.8) (57.3) (83.6) (130) (185) (246) (220) OFOFO FOFOF. OFOFOFOFOFOFDF 1875--1879 1880--1884 1E85--1889 1890--1994 1B95--1899 1900--1904 1905--1909 1910--1914 1915--1919 1920--1924 1925--1929 1930--1934 1935--1939 1940--1944 1945--1949 1950-1954 0.043 0.089 0.145 0.156 0.195 0.234 0.295 0.341 0.373 0.522 0.574 0.601 0.785 1.00 0.617 0.568 - 0.4 - 0.4 0.5 0.5 - 0.6 2 o.a 2 1.3 - 0.9 - 0.7 1.0 - 1.2 - 1.3 2 1.8 4 1.8 2 1.9 1 2.7 4 4.2 5 2.8 3 2.4 - 1.4 1 1.9 - 2.2 4 2.3 5 3.3 3 3.4 1 3.5 5 5.0 12 7.9 5 5.3 1 0.9 - 1.9 2 2.5 4 3.4 1 4.0 4 4.3 10 6.0 B 6.2 10 6.4 10 9.0 1014.3 1 2.0 1 3.4 3 4.6 5 6.0 6 8.3 7 9.9 13 10.5 17 14.9 17 15.3 18 15.6 24 22-2 6 6.3 5 4.1 1 4.2 4 7.3 1 5.0 6 0.5 6 6.9 13 11.8 8 9.0 19 15.4 11 12.4 20 21.2 2314.7 29 25.2 2215.7 23 26.8 21 22.1 43 37.7 20 22.6 40 38.9 25 23.2 3 7.9 4 6.3 2 2.3 1 5.3 6 9.4 11 11.1 19 15.1 26 19.7 34 27.1 37 32.2 35 34.2 36 48.3 6 10.3 2 3.0 4 6.S 14 12.0 15 14,0 19 18.9 26 24.7 41 34.0 43 407 36 43.4 10 12.4 1 3.1 10 7.1 16 12.3 IS 14.4 16 19.4 22 25.2 33 34.9 39 42.4 11 9.0 6 2.5 7 5.5 12 9.8 16 11.7 15 15.7 20 20.3 24 28.5 1 7.1 1 0.9 4 2.2 6 4.1 5 4.S 8 6.7 5 8.8 1 2.4 1 Incidence rate -- K, per 100 000 person-years in parentheses. 2000--2040. The predicted annual number among men born before 1955 peaks around the year 2015 by 93 cas es. For all men, when a relative risk of 50% of that of the 1940--1944 cohort for men was assumed, a peak in 2020 by 110 annual cases was found. The figure levels at about 80 annual cases over the years 2030--2040. The annual asbestos consumption in Denmark in 1910--1993 is shown in bars in figure 2. The import was greatest during 1965--1979 (approximately 30 000 tons per year) and decreased to 704 tons in 1990--1993. Table 3 shows, like table 2, the observed number of malignant mesotheliomas above the expected number. The numbers were derived from the model of period of diagnoses and age at diagnosis. The maximum effect of period occurs for the period 1983--1988, which had a 114 Scand J Work Environ Health 2000, vol 26, no 2 relative risk of 1.01, the goodness-of-fit having been eval uated by Pearson's x2-test (X^SO.5, df=97, P=0.89). An analysis of the variables birth cohort, age, and period of diagnosis was also done, and it gave no better fit Discussion The data of Danish cancer cases diagnosed since 1943, as registered in the Danish Cancer Register, is almost complete (10), However some misclassification of mes othelioma cases bas occunsd (23), and this misclassification complicates the interpretation of the results. "* Obs, * Exp. * Men bom before-1955 All men Figure 2. Observed (Obs) and expected (Exp) (fitted) number of cases of malignant mesothelioma in 1943-- 1993. Values of the annual number of cases for men bom before 1955 and for all men predicted on the assumption of a relative risk of 50% of the 1940--1945 birth cohort The annual asbestos consumption in Denmark In 1910-- ru> 1993 is shown as the 5-year average in bars. Table 3. Cases of malignant mesothelioma among Danish men in 1943--1993 and the fitted numbers based on a period-of-diagnosis analysis. Each cell shows the observed (0) number of mesothelioma cases next to the fitted (F) number derived from the period-ofdiagnosis model by multiplying the population person-years (not shown) by the product of k, and pc. Year of birth Relative Age group (years)1 risk ------------------------------------------:------ ----------------------------------- :--------------- 30--34 35--39 40--44 45--49 50--54 55--59 60--64 (0.66) (2.22) (418) (7.76) (19.7) (30.8) (57.3) 65--69 (83.6) 70--74 (130) 75--73 80--84 (185) (246) 85--39 (228) 0F 1943--1947 1948--1952 1953--1957 1958--1962 1963--1967 1968--1972 1973--1977 1978--1982 1983--1987 1988--1992 1993 0.093 0.107 0.202 0.4 0.522 0.695 0.78 0.838 1.01 1 0.882 _ 0.1 - 0.1 1 0.2 1 0.4 . 0.5 2 0.8 2 1.1 1.3 - 1.4 0F . 0.3 - 0.4 - 0.7 2 1.3 4 1.6 2 2.1 1 2.6 4 3.5 5 4.5 3 4.1 0F ` 0.5 1 0.6 - 1.2 4 2.3 5 3.0 3 3.8 1 4.2 5 4.9 12 7.3 5 7.9 i 1.3 0F 0.8 2 1.0 4 2.0 1 4.1 4 5.2 10 7.0 8 7.3 10 7.7 1010.1 1012.4 1 2.5 0 F0 F 1 1.4 3 1.8 5 3.8 6 8.2 711.0 13 14.3 17 16.3 17 16.3 18 19.2 24 20.7 6 4.0 1 1.6 1 2,0 6 4.3 8 9.3 11 13.3 23 18.1 2219.9 21 21.5 20 24.2 25 23.4 4 4.3 0 F0 F0 F 5 2.2 4 2.7 5 6.6 13 12,4 19 17.6 20 25.6 29 29.6 23 31.0 43 37.5 40 34.8 3 6.0 2 2.1 1 2.7 2 2.6 6 5.6 4 5.4 11 12.0. 14 11.4 19 17.3 15 16.0 26 24.3 19 23.3 34 30.6 26 28.4 37 33.8 41 33.4 35 39.6 43 41.7 36 39.6 36 40.4 6 6.8 10 7.3 0 FO F 1 4.2 10 9.1 16 12.7 18 18.1 18 22.2 22 25.8 33 34.2 39 35.7 11 6.1 6 5.4 7 7.6 12 11.0 16 13.6 15 15.9 20 20.6 24 22.8 1 4.3 0F 1 2.2 4 3.3 6 4.2 5 5.1 3 6.6 5 7.2 1 1.4 * Incidence rate -- k, per 100 000 person-years in parentheses. Some cases of malignant mesothelioma were diag registration until today is unlikely to be an artefact (26). nosed at autopsy. In a study (7) of the mesothelioma in Similar increases have been seen in other countries (6, cidence rate in Denmark in 1943--1992,25% and 29.5% 13,14,27). . of the cases among men and women, respectively, had a The larger fraction of mesothelioma of the peritone survival of 0 months, and most of these are likely to have um in women may be due to a misclassification of can been diagnosed at autopsy even though perioperative cers of the ovaries. In a Danish study about 30% of the mortality might have been of some importance. During peritoneal mesothelioma cases among women were found the 1970s, and particularly after the procedures changed to be misclassified ovarian or gastrointestinal tumors for the autopsy requests in 1990, the rate of autopsy in (23). Denmark declined from 45% in 1970 to 16% in 1990 In the Poisson regression analysis, a log-linear mod (24). A Danish study concluded that a decrease in the el with the parameters age and birth cohort was chosen frequency of autopsy leads to an underestimation of the because of the possibility of comparison with the results incidence rate of rare cancers (25), Malignant mesothe of Peto and his co-workers (14). The analysis was based lioma is such a cancer. only on cases among men because of the relatively low The 12--13-fold increase in the male incidence number of cases among women (table 1) and the possi rate of malignant mesothelioma since the beginning of i ble misclassification of peritoneal mesotheliomas among 115Scand J Work Environ Health 2000, vol 26. no 2 women (23). Because asbestos is considered to be the only important risk factor for malignant mesothelioma, other possible risk factors were omitted from the model. Smoking was also omitted because of no evidence of an effect on the risk of malignant mesothelioma in contrast to lung cancer, for which an important synergistic effect has been demonstrated (28). The goodness-of-fit, evaluated by Pearson's j^-test (21), suggests that the age-birth cohort model has a poor fit, with a nearly significant P-value of 0.11 of the dif ference between the observed and the estimated values. This occurrence could be due to the period of diagnosis being a stronger parameter than the cohort of birth. As in the study by Peto and his co-workers (14) the number of cases and the short period at risk in the younger age groups, who have not had the same exposure level as the older groups, make the estimates for these groups uncer tain. The structure of the synthetic birth cohorts makes the small changes in the data even harder to detect (21). The results of the study by Peto and his co-workers (14) are based on mortality data, but the average surviv al time, being only about 7 months after the diagnosis (7), makes the mortality and the incidence rates compa rable. The prediction of future incidence rates for malig nant mesothelioma was done in a manner similar to that of Peto and his co-workers (14), . The prediction of the number of new cases of malig nant mesotheliomas is based on the assumption that men bom after 1955 have half the risk of the 1940--1944 co hort. This assumption is made under the consideration that banning the use of asbestos in the industry and im proving the work environment cannot eliminate all ex posure to asbestos, and similar assumptions have been made in recent studies (11,12,14). The risk of mesothelioma from asbestos in the work environment was fust described in 1960 (29), and the gradual improvements introduced in the work environ ments hereafter favors a peak in incidence rates around the year 1995, If the asbestos consumption is considered an estimate of asbestos exposure level and an average latency of 35 years is used, the maximal incidence rate cannot be expected until the year 2010. The fit of the model using period of diagnosis being the better of the 2 models used calls for some caution in interpreting the results of the predictions made by using the birth cohort in the analysis. The period of diagnosis cannot readily be utilized in calculating the future number of cases of malignant mesothelioma because of nonex isting reliable predictions of future asbestos exposure. Prior exposure can only be quantified by the total con sumption of asbestos, which is a very rough estimate of the individual exposure to asbestos. The asbestos import ed after the ban has comprised chiysodle fibers, used for brakes and pipefittings, while the import of amphiboles has been completely banned (4, 5). Information on the 116 Sound J Work Environ Health 2000, vol 26. no 2 distribution of the different fiber types, relevant to the risk of mesothelioma, is not available, not even for amphiboles and serpentine fibers. If a prediction of the future number of mesothelioma cases were to be carried out on the basis of an analysis of the period of diagnosis and age, it would be essential to have reliable estimates of future environmental expo sure levels to asbestos. These estimates cannot be made within the limits of this study. In conclusion, with careful interpretation of the re sults, the annual number of malignant mesothelioma cas es can be expected to increase steadily until 2010. No or little effect of banning the usage of asbestos can be ex pected until 2015 or later. Acknowledgments We wish to thank statistician Gerda Engholm, Statistics Denmark, for doing the statistical modeling of the data and introducing the idea of trying the effect of age and period of diagnosis. Statisticians Birtbe Lykke Thomsen and Mette Suntum, Danish Cancer Society, have been helpful in interpreting the results. Financial support for the statistical analyses was pro vided by the Danish Cancer Society, grant 5622312/9172. References 1. Storm HH, Pthl J, Michelsen E, Nielsen AL, editors. Cancer incidence in Denmark 1993. Copenhagen: Danish Cancel So ciety, 1996. 2. International Agency for Research on Cancer (1ARC!. Asbes tos. Lyon. France: LARC, 1973. Monograph on the evaluation of the carcinogenic risk of chemicals to man, vol 14. 3. Olsen JH, Andersson M. Asbcstinduceret cancer i Danmark [Cancer induced by asbestos in Denmark). Ugeskr Laeger 1986;14B(49):3328--33. 4. Ministry of Labour. Arbejdsministeiiets bekendtgoreise nr 660 af 24, September 1986 om asbest [Departmental order of the Ministry of Labour no 660, September 24,1956, concern ing asbestos). Copenhagen: Ministry of Labour, 1986. 5. Ministry of Labour. Arbejdsministeriets bekendtgerelse nr 984 af 11. december 1992 [Departmental order of the Minis try of Labour no 984, 11 December 1992, concerning the usage of asbestos], Copenhagen: Ministry of Labour; 1992. 6. Jarvholm B, England A, Albio M. Pleural mesothelioma in Sweden: an analysis of the incidence according to the use of asbestos. Occup Environ Med 1999:56:110--3. 7. Kjaergaard J, Michelsen EV. Malignt mesoteliom: incidcns, overlevelse og relativ risiko i udvalgte kommuner 1943-- 1992 [Malignant mesothelioma: incidence, survival and rela tive risks in selected municipalities 1943--1992). Ugeskr Laeger 1997; 159(31}:4756--61. 8. Htmcharek M. The biomedical and epidemiological charac teristics of asbesros-related diseases: a review. Yale 1 Biol Mod 1986;59:435-51. 9. Selikoff II. Hammond EC, Seidman H. Latency of asbestos disease among insulation workers in the United States and Canada.- Cancer 1980;46:2736--40. 10. Storm HH, Michelsen EV, Oemmensen IH, Pihl J. The Dan ish Cancer Registry -- history, content, quality and use: Dan Med Bull 1997;44:549-53. 11. Peto J, Decarli A, ia VC, Levi F, Negri E. The European mesothelioma epidemic. Hr J Cancer 1999;79(3--4):666-- 72. 12. Qg AO, Bignon 1, Valleron AJ. Estimation of the past and future burden of mortality from mesothelioma in France. Oceup Environ Med 1998:55(11):760--5. 13. Price B. Analysis ofcurrent trends in United States mesotheli oma incidence. Am J Epidemiol 1997;145(3):211--S. 14. Peto J, Hodgson JT, Matthews HE, lones JR. Continuing increase in mesothelioma mortality in Britain. Lancet 1995;345:535-9. 15. World Health Organization (WHO). Manual of the interna tional statistical classification of diseases, injuries, and causes ofdeath: 1955 revision (7th). Geneva: WHO, 1957. 16. World Health Organization (WHO). International classifica tion of diseases for oncology (ICD-O). Geneva: WHO, 1976. 17. Frdnip E. Bisgaard MP. Olescn PE. editors. Statistical year book 1996. Copenhagen: Statistics Denmark, 1996, 13. Smith P. Comparison between registries: age-standardised rates. In; Muir C, Waterhouse J, Mack T, Powell J, Whelan S, editors. Cancer incidence in five continents, volume V. Lyon (France): International Agency for Research on Cancer (IARC), 1987:790--5. IARC scientific publications, vol 11. 19. Breslow NE, Day NE. Statistical methods in cancer research; vol II (The design and analysis of cohort studies). Lyon: International Agency for Research on Cancer (IARC), 1987. [ARC scientific publications, vol 82, 20. Breslow NE, Day NE. Dawis W, editors. Statistical methods in cancer research; vol I (The analysis of case-control stud- | ics). Lyon (France): International Agency for Research on Cancer (IARC), 1980. IARC scientific publications, vol 32. ' 21. Roush GC, Holford TR, Schymura MJ. White C. Cancer risk and incidence trends: the Connecticut perspective. Washing ton (DC): Hemispere Publishing Corporation, 1987. 22, Statistics Denmark. Import and export, 1910--93. Copenha gen; Statistics Denmark, 1993 23. Nielsen AM, Olsen JH, Madsen PM, Francis D, Almind M. Peritoneal mesotheliomas in Danish women; review of his topathologic slides and history of abdominal surgery. Acta Obstct Gynecol Scand 1994;73:581--5, 24. Petri CN. Decrease in the frequency of autopsies in Denmark- after the introduction of a new autopsy act. Qual Assur Health Care 1993;5:315-8. . 25. Storm HH, Andersen J. Autopsihyppighed blandt eancerpa- tienter i Danmark 1971--1980 [Utilisation of autopsies in cancer patients in Denmark 1971--1980]. Ugeskr Larger 1986;143:1110--4. 26. Andetsson M. Olsen JH. Malignt mesoteliom i Danmark 1943--1990: krscftstatistik 9 [Malignant mesotheliomas in Denmark 1943--1980; cancer statistics 9). Ugeskr Laeger 1984;146:1085-7. 27. Karjalainen A, Pukkala E, Mattson K, Tammilehto L, Vainio H. Trends in mesothelioma incidence and occupational mes otheliomas in Finland in 1960--1995. Scand J Work Environ Health 1997;23(4):266--70. 28. International Agency for Research on Cancer (IARC). Over all evaluation of carcinogenicity: an updating of IARC mono graphs volumes 1 to 42. Lyon (France): IARC, 1987. IARC monographs on the evaluation of carcinogenic risks to hu mans, suppl 7. 29. Wagner JC, Sleggs CA, Merchaud P. Diffuse pleural mes othelioma and asbestos exposure in the North Western Cape Province. Br J Ind Med 1960;17:260-71. Received for publication; 9 March 1999 Scand J Work Environ Health 2000, vol 26, no 2 117