ferent lifetime risk estimates, particularly for persons exposed early in life. Furthermore, it was not feasible to evaluate all possible models that might be used to describe the LSS data.
The form of the model is particularly uncertain for cancers of specific sites. In most cases, the parameters that quantify the effects of age at exposure and attained age (see Equation 12-2) were taken to be those estimated in analyses of all solid cancers as a single outcome. However, for most sites, data were consistent with a wide range of values for these parameters. Even the form of the model might vary by cancer site. Although this was not investigated by the committee, it is doubtful that data for most specific sites would allow one to distinguish among various models. Finally, once again it should be noted that because all members of the LSS cohort were exposed at the same time, effects of age at exposure are confounded with secular trends (discussed further above and in Annex 12B).
Models based on either the ERR or the EAR as a function of dose, sex, age at exposure, and attained age can provide reasonable descriptions of the data, and the committee has presented risk estimates based on both choices. In its application, the differences in lifetime risks obtained for the two choices largely reflect differences in the method of transport to the U.S. population as discussed above. However, the two models could give somewhat different risk estimates even if applied to the LSS cohort. Preston and colleagues (1991) present lifetime risk estimates for solid cancer mortality in the LSS cohort. Estimates based on ERR and EAR models were similar for those exposed at ages of 30 or more, but for those exposed as children, estimates based on the EAR model were about 25% lower for men and 25% higher for women than estimates based an ERR model. (NOTE: The model used by Preston and others is the RERF model shown in Equation (12-2).)
The above section “Use of the Committee’s Preferred Models to Estimate Risks for the U.S. Population” describes the committee’s choices regarding several issues. Since data are inadequate to indicate clearly the correct choices, all are sources of uncertainty. The committee has quantified the uncertainty from its choice regarding transport of risks from a Japanese population to a U.S. population and from its choice regarding the DDREF for estimating risks from exposure to low doses and low dose rates. Additional sources of uncertainty which have not been quantified, are projection of risks over time, which is primarily important for persons exposed early in life, and estimating risks from low-energy X-rays, which is of importance in estimating risks from diagnostic medical procedures (for a discussion of this subject, see Chapter 1, “Different Effectiveness of γ-rays and X-rays”).
Although the committee has analyzed only data from the LSS cohort, consideration has been given to published analyses of data from several medically exposed cohorts. For breast and thyroid cancers, the committee’s recommended models are based on published analyses of pooled data from the LSS and from medically exposed persons. This section briefly describes results from relevant medical studies and their compatibility with BEIR VII models.
A number of studies involving radiation exposure for medical reasons are described and discussed in Chapter 7. Although these studies have increased our general knowledge of radiation risks, not all of them are suitable for quantitative risk assessment. Many studies lack the sample size and high-quality dosimetry that are necessary for precise estimation of risk as a function of dose, a point that is illustrated by the large confidence intervals for many of the risk estimates shown in Tables 7-2 to 7-6. Studies of therapeutic exposures often involve very large doses (5 Gy or more) where cell killing may lead to underestimation of the risk per unit dose. In addition, the presence of disease may modify radiation-related risk especially for organs directly affected by the disease, such as the lung in tuberculosis fluoroscopy patients and the breast in benign breast disease patients. Furthermore, studies frequently include only a limited range of exposure ages and thus provide little information on the modifying effect of this variable. For example, studies of persons treated with radiation for solid cancers are often limited to persons exposed at older ages; by contrast, most studies of thyroid cancer risk from external exposure involve exposure in childhood (Ron and others 1995a).
Often there is interest in comparing results from different studies to gain information on the modifying effects of factors that may differ among studies. For example, Chapter 10 (“Transport of Risks”) discusses estimates from medical studies from the standpoint of comparing risks for cancer sites where baseline risks differ greatly for Japanese and Caucasian subjects. Most medically exposed cohorts differ in more than one way from the LSS cohort (e.g., baseline risks, size of doses, dose fractionation, age at exposure), making it difficult to interpret risk estimate comparisons. It must be acknowledged that data are inadequate to develop models that take account fully of the many factors that may influence risks. This is illustrated effectively in analyses by Preston and colleagues (2002a) of breast cancer incidence in eight cohorts, where it was not possible to find a common model that adequately described data from all eight cohorts.
In the material below, findings from selected studies are discussed that were not used in developing the BEIR VII models. The material is organized by cancer categories.