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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2
cluded: sampling variability in the estimated ERRs (including uncertainty in parameters expressing modification by age at exposure, sex, etc.), correction for random and systematic errors in A-bomb survivor dosimetry, extrapolation of risk from high to low doses and low dose rates (expressed as uncertainty in the DDREF), transfer of risk estimates from A-bomb survivors to a U.S. population, and modification by smoking history (lung cancer only). With the exception of sampling variability, the uncertainty distributions for the individual sources were based on informed but nevertheless subjective judgments.
ANNEX 12B:COMMITTEE ANALYSES OF DATA ON THE LSS COHORT TO DEVELOP BEIR VII MODELS FOR ESTIMATING CANCER RISKS
Chapter 12 describes models that were used by the committee to estimate cancer risks. These models were based primarily on analyses of A-bomb survivor cancer incidence data (1958–1995) and, to a lesser extent, mortality data (1950–1997), with consideration of published analyses of data from selected studies involving medical exposures. This annex presents details of analyses of data from the LSS cohort of atomic bomb survivors that were conducted to develop these models. Analyses of cancer mortality data were conducted by the committee. Because the most recent cancer incidence data were not yet available outside of RERF, analyses of these data were conducted under the direction of the committee by RERF investigators who served as agents of the Academy.
The committee’s selected models for estimating solid cancer risks allow the ERR or EAR to depend on both age at exposure and attained age. Both the ERR and the EAR decline with increasing age at exposure. The ERR also declines with increasing attained age, while the EAR increases with increasing attained age. The BEIR VII models are similar to the model used in recent analyses of atomic bomb survivor data by RERF investigators, except that with the BEIR VII model, the ERR and EAR decrease with age at exposure only over the range 0–30 years with no further decrease after age 30. The material that follows describes analyses that were conducted to evaluate several possible models for solid cancer risks, including models that allow for dependence on age at exposure alone, on attained age alone, on time since exposure instead of attained age, and on the use of different functional forms to express these dependencies. Also evaluated are several models for leukemia risks.
Aproach to Analyses
Analyses of cancer incidence were based on cases diagnosed in the period 1958–1998. Analyses of mortality from all solid cancers and from leukemia were based on deaths occurring in the period 1950–2000 (Preston and others 2004), whereas analyses of mortality from cancer of specific sites were based on deaths occurring in the period 1950–1997 (Preston and others 2003). Both ERR models and EAR models were evaluated. Methods were generally similar to those used in recent reports by RERF investigators (Pierce and others 1996; Preston and others 2003) and were based on Poisson regression using the AMFIT module of the software package EPICURE (Preston and others 1991). Confidence intervals (95%) were usually calculated as the estimate plus and minus 1.96 times the standard error. For estimates of linear coefficients of dose, these were calculated on a logarithmic scale. Occasionally (as noted) confidence intervals were calculated using the likelihood profile. All p-values were based on chi-square approximations of likelihood ratio tests. These are based on differences in the maximized log likelihood statistics, often referred to as deviances.
To fit ERR models, baseline risks were handled by stratifying on gender, city of exposure (Hiroshima or Nagasaki), age at exposure, and attained age as described by Pierce and colleagues (1996). To fit EAR models, baseline risks were modeled using the parametric model described by Preston and coworkers (2003). For leukemia, the parametric model is that described by Preston and coworkers (2004). The risk of radiation-induced cancer was modeled as described in the sections that follow.
All analyses were based on newly implemented DS02 dose estimates. Doses were expressed in sieverts with a constant weighting factor of 10 for the neutron dose; that is, the doses were calculated as γ-ray absorbed dose (grays) + 10 × neutron absorbed dose (grays). Analyses were adjusted for random errors in doses using an approach described by Pierce and colleagues (1990) and developed from DS86 dose estimates. Preston and colleagues (2004) note that it has not yet been determined if modification of these methods is needed for DS02 dose estimates. Unless stated otherwise, doses are truncated to correspond to the 4 Gy kerma level.
The DS02 system provides estimates of doses to several organs of the body. For site-specific cancers the committee used dose to the organ being evaluated, with colon dose used for the residual category of “other” cancers. The weighted dose, d, to the colon was used for the combined category of all solid cancers or all solid cancers excluding thyroid and nonmelanoma skin cancer. This choice was made to achieve comparability with analyses by RERF investigators. Reference to an average organ dose—approximated, say, by the dose to the liver—might be more realistic for the analysis of solid cancers combined and would likely lead to about a 10% increase in the values of the weighted dose, d, and thus a reduction of about 10% in the risk coefficients (Kellerer and others 2001). However, the committee’s estimates of the risk for all solid cancers are obtained by summing estimates for individual organ sites (based on doses to these organs), and thus should not be subject to this bias.
It has also been suggested that a weighting factor of roughly 30 for the neutron absorbed dose might be a better