Health Effects of Exposure to Radon BEIR VI (1999) / Chapter Skim
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3 Models and Risk Projections
3 Models and Risk Projections
Pages 69-116
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From page 69... ...
Those two decisions follow those of the BEIR IV committee. However, the rationale for our model is supported more strongly than was that of the BEIR IV committee, being grounded in the biologic considerations developed in chapter 2 and in the stronger body of observational evidence provided by the pooled data from the studies of underground miners, as well as a meta-analysis of the reported 8 case-control studies of residential radon exposure and lung cancer.
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From page 70... ...
Use physical dosimetric models of the lung to estimate alpha-particle dose to lung-airway epithelium for indoor radon exposure.
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From page 71... ...
First, the mechanisms of radon-induced carcinogenesis must be known with sufficient certainty before an appropriate biologically motivated model can be constructed. Despite the considerable amount of information summarized in chapter 2, the committee recognized that current knowledge of radiation cancer mechanisms remains incomplete and any postulated model would necessarily be an oversimplification of a complex process.
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From page 72... ...
RATIONALE FOR THE COMMITTEE'S CHOSEN METHOD FOR RADON RISK ESTIMATION The committee critically assessed the principal approaches (see Figure 1-3) that could be used to estimate the risk associated with exposure to indoor radon, with respect both to sources of data for developing risk models and to techniques for modeling.
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From page 73... ...
In principle, residential studies yield the most relevant risk estimates, because they relate directly to the population of interest. However, because of the very low risk associated with exposures at residential levels, risk estimates obtained from these studies, even estimates based on meta-analysis of several studies, are very imprecise.
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From page 74... ...
All models used risk estimates derived from the studies of miners. The earliest risk models specified effects of exposure in terms of the absolute excess risk of lung cancer from radon-progeny exposure.
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From page 75... ...
were preferable to models of the absolute excess risk. Recent descriptive models for lung-cancer risk associated with radon-progeny exposure have also modeled the relative risk rather than the absolute risk.
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From page 76... ...
The committee used a relative-risk model that relates lung-cancer rate in miners to their occupational exposure to radon. In the analysis, exposure refers to occupational exposure to radon progeny during employment in underground mines, and relative risks refer to the additional risks associated with occupational exposure to radon progeny beyond the background risk from lung cancer, which reflects other exposures, including indoor radon.
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From page 77... ...
Since the 1994 publication of the original pooled analysis by Lubin and colleagues (1994a) , data from 4 studies (Chinese tin miners and the Czechoslovakia,1 Colorado and French uranium miners)
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From page 78... ...
Because of the computational difficulties of merging case-control data with cohort data, only the data from the Beaverlodge cohort study with the original exposure estimates were used in the committee's analysis. Analysis of Pooled Data from Different Studies In the development of risk models, it is important to take account of the totality of evidence from all relevant studies.
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From page 79... ...
Such differences can lead to heterogeneity in risk estimates. Heterogeneity can be partially addressed by adjusting for modifying factors, such as exposure rate, on which data are available.
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From page 80... ...
Briefly, they found that models that took into account time since exposure, attained age, and either duration of exposure or concentration of radon progeny as an indicator of exposure rate provided equally good fits to the miner data. Models with fewer than 3 of the modifying factors did not provide comparable fits to the available data.
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From page 81... ...
The mean duration of exposure for the miners was about 6 yr, about one-tenth the duration of residential exposures. Thus, mean exposure rates of miners were about 100 times those of residents of typical houses.
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From page 82... ...
. , 1me-slnce-exposure wlnuows 0.55 fix 100 6.11 85-14 1.00 1.00 85-14 1.00 1.00 815-24 0.76 0.72 815-24 0.81 0.78 825+ 0.31 0.44 825+ 0.40 0.51 Attained age ¢<55 1.00 1.00 ¢<55 1.00 1.00 ¢55-64 0.57 0.52 ¢55-64 0.65 0.57 ¢65-74 0.34 0.28 ¢65-74 0.38 0.29 ¢75+ 0.28 0.13 ¢75+ 0.22 0.09 Duration of exposure Exposure rate (WL)
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From page 83... ...
(<100 WLM) No restrictions Cohort China77116980 Czech1577705 Colorado1522336 Ontario180231291 Newfoundland21241 18 Sweden173679 New Mexico81169 Beaverlodge424965 Port Radium202557 Radium Hill525354 France223 345 All data combineda Lung-cancer deaths Nonexposed1 151 151 13 Exposed3535622674 Person-years Nonexposed274,161274,161271,457b Exposed454,159564,772883,996 Mean values for exposed lung-cancer cases WLM19.740493.6 WL0.91.24.1 Years since last exposure1717.413.8 Duration of exposure, yr5.46.614.1 Attained age, yr5058.658.5 aTotals exclude 115 workers and 12 lung-cancer cases that were in both the Colorado and New Mexico studies.
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From page 84... ...
in the restricted analyses were consistent with the patterns with the unrestricted data for all factors except attained age. The excess RR declined with time since exposure and exposure rate, and increased with exposure duration.
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From page 85... ...
Thus, if exposures outside this 30-year period influence lung-cancer risk, as suggested by the miner data, then the 14% excess relative risk at 148 Bqm-3 from indoor studies is a biased estimate of the lifetime relative risk at this concentration and therefore cannot be used to estimate attributable risks for a population. BEIR VI RISK ASSESSMENT FOR LUNG CANCER IN GENERAL POPULATION Introduction To extrapolate the risk model from the BEIR VI analyses of miner risks to residential exposures, several assumptions must be made (Table 3-6~.
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From page 86... ...
FIGURE 3-1 Contributions to the population attributable risk as a function of radon concentration in U.S. homes, based on the BEIR VI risk models.
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From page 88... ...
In addition, as discussed above, exposureresponse relationships estimated from the observational data in miners with the lowest exposures, and from the case-control studies of indoor radon, are consistent with linearity (Figure 3-2~. Another critical issue in the extrapolation of risks to the general population is that exposure rates in homes are a thousand-fold to a hundred-fold less from those in most mines.
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From page 89... ...
and on the meta-analysis offers some support for using the committee' s models in adjusting for exposure-rate effects at residential doses. In addition to differing in exposure levels and exposure rates, the general population differs from the miner cohorts in including females and persons exposed at all ages and in tobacco-smoking and other exposures.
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From page 90... ...
As in the BEIR IV report, we applied the same risk model to baseline rates for males and females, assuming a multiplicative joint association for exposure and sex; that is, the ratio of ERR to exposure is assumed to be the same for males and females, given specific ages, exposure rates and times since exposure. The background lung-cancer risk for females is lower than that for males, so this assumption results in a smaller lifetime absolute excess risk for females attributable to radon exposure.
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From page 91... ...
However, uncertainty analyses of population-risk projections were conducted to estimate the significance of deviations from 1. Measures of Risk To assess the population lung-cancer risk posed by indoor radon, the model for the exposure-response relationship is applied to the observed distribution of residential radon exposures received by the U.S.
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From page 92... ...
The risks have been corrected for competing causes of death by using standard lifetable methods as described in BEIR IV. Relative-Risk Estimates Lifetime Relative Risks LRRs were computed with the committee' s exposure-age-concentration and exposure-age-duration models (Table 3-5~.
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From page 93... ...
The ARs for the various risk models used 1985-1989 mortality data (for both lung cancer and all causes of death) and the same distribution for domestic radon concentration as shown in Table 3-7.
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From page 94... ...
Attributable Risk Accounting for Smoking Status The committee's two risk models were initially developed without explicitly incorporating the available data on smoking status. For estimation of the number of lung cancers in the general population due to indoor exposure to radon progeny, the BEIR IV committee and other groups have recommended that the same
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From page 95... ...
There were insufficient data to develop a risk model for never-smokers directly, but we can adjust the risk models on the basis of the relative difference in the exposure-response relationships for ever-smokers and never-smokers. When only data on miners for whom some smoking information was available were used, the overall ERR/0.0035 Jhm-3 was estimated to be 1.02% among neversmokers (95% CI,0.15-7.18%)
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From page 96... ...
In the exposure-age-duration model, the estimate of 0.0055 was reduced to 0.0050 for ever-smokers and increased to 0.011 for never-smokers. ARs for indoor radon-progeny exposure in the US for ever-smokers and neversmokers, based on risk models with and without this adjustment, are given in Table 3-9.
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From page 97... ...
Effect of Radon Mitigation on Attributable Risk The overall AR describes the anticipated consequences of virtual elimination of indoor radon exposures under the committee's risk models. A more-realistic assessment of the reduction of attributable risk due to radon exposure mitigation focuses on exposure-reduction scenarios that might actually be achieved.
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From page 98... ...
TABLE 3-11 Effective attributable risks (EARa) for lung cancer from residential radon exposure to radon using 1985-89 U.S.
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From page 99... ...
CEffective attributable risk estimates the proportion of radon-induced lung-cancer deaths which could be prevented if the distribution of radon concentration in houses was modified. In this example, EAR is based on reducing the radon concentration in all homes above 148 sqlm3 to a level between the outdoor level and 148 sqlm3 (4 pCiL-l)
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From page 100... ...
Errors in data on exposure to radon and radon progeny including estimated cumulative exposures, exposure rates and durations; c) Limitations in data on other exposures including data on smoking and on other exposures such as arsenic.
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From page 101... ...
discusses sources of uncertainty in BEIR IV risk estimates; much of this discussion is relevant, at least in general terms, to the BEIR VI risk estimates. Uncertainties in Parameter Estimates Derived from Underground-Miner Data Uncertainty Due to Sampling Variation Uncertainty resulting from sampling variation differs from uncertainty of most other sources in that it can be quantified using statistical methods.
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From page 102... ...
However, analyses restricted to exposures below 0.175 Jhm-3 and below 0.350 Jhm-3 led to attributable risk estimates that were very similar to those obtained with the committee's recommended models based on the full miner data set. Miners exposed at those low levels were employed predominantly in later periods when exposure-assessment methods had improved substantially, and their exposure estimates were probably affected to a lesser degree by measurement error than those of the miners who worked in the earlier periods.
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From page 103... ...
Shape of the Exposure/Exposure-Rate Response Relations Cumulative exposures and exposure rates were generally much higher in underground mines than in homes, consequently, it might be thought of that the most-critical aspect of the committee's model development process is the choice of method for extrapolating risks to residential exposures. However, the committee's recommended risk models included parameters that specifically estimated effects at average exposure rates less than 0.03 Jm-3 (0.5 WL)
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From page 104... ...
However, we did not calculate risks posed by radon exposure of former smokers, because we lacked data on changes in lung-cancer mortality in miners in relation to age and time since stopping smoking. UNCERTAINTY ANALYSIS The previous section identified factors that can contribute to uncertainty in radon risk estimates.
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From page 105... ...
The population attributable risk depends on the risk model used to describe the exposure-response relationship between radon and lung cancer, the distribu
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From page 106... ...
Because the uncertainties in the model parameters are largely statistical, the uncertainty distributions reflecting only uncertainty in the parameters of the committee's risk models (Figure 33, case I) can be used to obtain approximate confidence intervals for the AR.
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From page 107... ...
U) 9,~ 10 107 Exposure-Age-Concentration Model I ,N' o II III 0.2 0.3 0.4 Exposure-Age-Duration Model II III 0 0.1 0.2 0.3 0.4 Attributable Risk FIGURE 3-3a Uncertainty distributions for the population attributable risk (AR)
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From page 108... ...
III _ ~1 o 0.2 Attributable Risk 0.3 0.4 FIGURE 3-3b Uncertainty distributions for the population attributable risk (AR) for females.
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From page 109... ...
homes are appropriate only if the models apply equally well at residential exposure levels. To address that issue, the committee also calculated 95% uncertainty intervals for the projected number of lung-cancer cases attributable to residential radon exposure by using the constant-relative-risk (CRR)
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From page 110... ...
Closely comparable statistical methods were applied by both the BEIR IV and BEIR VI committees. BEIR IV AND BEIR VI RISK MODELS The committee' s models are a direct extension of the BEIR IV model, which included parameters for time since exposure and attained age, but not exposure rate or exposure duration, as in the BEIR VI models.
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From page 111... ...
111 - lo OD J ~CD ID o ~ Q X UJ N o _ o X A ~CC)
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From page 112... ...
112 o Q o x o o us o E o x x 8 J 3 U' o o x .
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From page 113... ...
FIGURE 3-6 Predicted lifetime relative risk of lung cancer for males and females by "residential" radon concentration. Exposure occurs over a lifetime at a constant radon concentration.
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From page 114... ...
The committee entertained 2 categorical risk models in which the ERR was modified either by attained age and duration of exposure or by attained age and exposure rate. The ERR decreased with both attained age and exposure rate and increased with duration of exposure.
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From page 115... ...
The percentage of lung-cancer cases that can be attributed to residential exposure to radon is of particular interest for risk management. The committee used data from the National Residential Radon Survey in combination with its 2 categorical risk models to estimate the AR posed by residential radon exposures.
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From page 116... ...
On the basis of the committee's categorical risk models, reducing radon concentration in all homes that are above 148 Bqm-3 (4 pCiL-~) to below 148 Bqm-3 (4 pCiL-~)
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