Document da46bVBqq5NG0MwMyeqMmopkB

Quantitative risks of mesothelioma and lung cancer 577 Table 3. Additional data on pleural and peritoneal mesothelioma from cohorts with predominant exposure to crocidolite or amosite (but not both), and without reported quantified cumulative exposures Cohort No. Reference Process Fibre Sex Expected all cause morality Pleural No. % Excess mortality Peritoneal No. % Excess mortality 18 Jones et al. (1996) 0r 400* S3 13 14 3.5 19 Acheson et al. (1982) Gas masks 0 f 185 3 1.6 2 1.1 (Leyland group) 20 McDonald and oy mf 41* 3 7.3 6 14.6 McDonald (1978) 21 Hill et al. (1981) 0 0m S' 1 20 1 20 22 Levin et al. (1998) 1 am 133.6 4 3 2 15 23 Parolari et al. (1987) 1 a mf 115.1 2 1.7 i 0.87 24 Finkelsiein (1989) 1 a m 1.89 2 106 25 Acheson et al. (1984) 1 *y m 298.8 4 1.3 1,. 053 'Estimated as observed deaths less asbestos related deaths. ^Estimated assuming 75% mortality from age 31 to 68. tissue. If true, it is presumably related to the dynamics controlling the distribution of asbestos fibres around the body. Note that this relationship does not depend on the cumulative exposure, and is therefore not sub ject to the uncertainties attached to exposure esti mation. Whatever its physical/biological explanation, these observations imply that at least one of these out comes has a non-linear relationship with exposure. Fig. 5. Joint distribution of excess mortality from pleural and peritoneal mesothelioma, showing fibre type. (Note: Label size (area) roughly proportion to total mesothelioma numbers in each cohort). residuals for these two cohorts, the overall residual deviance for the inclusive data (model 2) indicates a satisfactory fit (/M>.22). If the two outliers are removed, the separate fibre model fits the data almost exactly, and the slopes for the two fibres are very similar (model 3) and higher (around 3.2) than the y for the fit including them. In either case the single >e model is rejected in favour of separate fits to the iwo fibre types, with similar slopes. The peritoneal rate is proportional to at least the square--perhaps as much as the cube--of the pleural rate. The. form of the relationship is unusual and some what surprising, since both outcomes reflect the effect of the same carcinogenic insult to the same type of Pleural mesothelioma and cumulative exposure To examine this question more closely. Fig. 6 shows a plot of excess mortality from pleural meso thelioma against cumulative exposure with cohorts represented by their fibre type code. Figure 7 shows a similar plot for peritoneal mesothelioma. The points for the pure amphibole cohorts show a clear pattern of alignment, with the slopes for pleural mesotheli oma less than 1 and those-for peritoneal mesotheli oma greater than 1. Table 5 summarises the results of Poisson regression fits to the relationship between percentage excess mortality from pleural cancer and cumulative exposure, and the observed data points and selected regression lines are shown in Fig. 6. The relationship is modelled as linear on a log scale for each variable, and therefore has the form P^ = A^C where Pp, is the percent excess mortality from pleural cancer, X is cumulative exposure and Aft and r are regression parameters. The corresponding predicted number of pleural cancers for a given cohort is Att)CEAi/\0Q (where EAdJ is expected all cause deaths adjusted to an age at exposure of 30). The parameters were esti mated by minimising the residual deviance between the observed and predicted numbers of pleural cancer for each (pure fibre) cohort It is clear that a wide range of slopes (r) are statisti cally consistent with the data. With independent fits to each fibre type the slopes are 0.62, 1.2 and 0.72 for crocidolite, amosite and chrysolite respectively.