Document 0q1OLJbyeMk8No2Ymj8ne7J5b

Quantitative risks of mesothelioma and lung cancer 567 this etTor is very small, but in an asbestos exposed cohort it may have a substantial effect. Leaving the miscoded mesotheliomas in the lung cancer count will overstate the true lung cancer SMR. Excluding them will in theory understate it, but only to the small extent that this error affects the population as a whole. The best available approximation to a true estimate of the risk is therefore to exclude the miscoded'mesotheliomas, and this has been done for this review. of 10. Details of this reassessed data were to be pub lished, but these have not so far appeared in print. It is therefore difficult to know whether to make an adjustment to the published estimates, and if so by how much. Similar comments may of course apply to other cohorts and introducing a correction might then diston rather than correct the overall picture, de Klerk and colleagues, developing estimates of environmen tal risk at Wittenoom (1992) use a factor of 4 without Derivation of cohort mean exposure estimates Mean exposure for cohorts was calculated in differ ent ways, depending on the available information. detailed discussion. The effect of using this adjusted exposure level is examined as a variant of the main analyses. When data was given for separate exposure groups, the cohort mean was calculated by weighting the indi Exposure-specific risk estimates vidual group means by the expected deaths from lung It is generally assumed that the most reliable guide cancer in the group. On the assumption that excess to dose-specific risk is provided by exposure analyses risk is proportional to cumulative exposure, this using estimates of individual exposure. This is clearly weighting preserves the same proportionality when the case when these individual exposure values can the results from subgroups with different exposures be accurately determined. However this assumption are aggregated, it is therefore the optimal statistical is very much not the case in the studies in this review. measure of aggregate exposure. Not only are there the inevitable problems of extrapo Where mean exposure values for individual dose lating earlier exposures on the basis of more recent categories were not given, the midpoints were used. measurements; there are also problems of convening The top exposure category was usually given as an the most usual historic measurements (in terms of open interval (e.g. exposures>!00 f/ml.yr): in these panicle counts) to the more relevant measure of fibre cases a value was chosen based on a view of the high counts. Direct fibre counting only became generally est likely exposure and the distribution of individuals used in the 1970s. across all exposure categories. It was assumed that In these circumstances it is at least arguable that where the highest category contains a relatively small global assessments of average exposure, set against proportion of the population, the category mean will overall mortality outcomes, should be preferred. be a smaller multiple of the lower band than other Exposure-response regressions with inaccurate indi wise. vidual exposure assignments will produce a slope For cohorts where results for exposure specific sub estimate biased downwards. Use of an overall assess groups were not given, the cohort mean was either ment will also minimise the error introduced by con given directly (cohorts 4, 13 and 15); derived from version from panicle counts to fibres, since these information given on the distribution of individual average conversion factors will represent a more doses (cohorts I and 7), or on the'exposure of internal accurate conversion for the totality of exposure than controls (cohort 17), or by multiplying a mean for a particular individual; exposure level by mean exposure duration (cohorts 8 However, the arguments are not all one way. Over and 14). Exposure estimates given in particle counts were converted to counts of `regulated fibres' (fibres with all mortality outcomes can only be assessed against some outside reference--usually (he regional or national population--and this may not represent a true baseline level for the exposed population in ques an aspect ratio greater than 3:1, and length>=5 tion. Assessment of an internal exposure response microns), using conversion factors calculated by the gives some check on (his issue. A complete absence report authors where possible. The most commonly of exposure response must cast some doubt on any used conversion was I mppcf (million panicles per overall excess being counted as a measure of risk (the cubic foot)=3 f/ml (fibres per millilitre), and this was Albin and Connecticut cohorts are examples of this). the value adopted for the Johns Manville cohort, Cohort-level risk measures were chosen for this where a conversion was not given. For the Massachu review both because these allow a wider range of data setts cohort, where the fibre involved was crocidotile i to be assessed than if attention is restricted to internal (rather than chrysolite as in the other cohorts with exposure response analyses and since (as argued particle counts), an independent expen hygienist was above) cohort-level exposure estimates ore likely to asked for an assessment (see Appendix B). be more accurate than individual exposures. The exposure estimates for Winenoom have been questioned by Rogers (1990) who hus suggested-- having rc-exumined some of the original samples Smoking using modem light and electron microscopy--that the The evidence on the joint effect of smoking and levels may have been underestimated by up to a factor asbestos exposure on lung cancer has been reviewed /