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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2
Current knowledge on the cellular and molecular mechanisms of radiation tumorigenesis tends to support the application of models that incorporate the excess relative risk projection over time.
The choice of models for the transport of cancer risk from Japanese A-bomb survivors to the U.S. population is influenced by mechanistic knowledge and information on the etiology of different cancer types.
A combined Bayesian analysis of A-bomb epidemiologic information and experimental data has been employed to provide an estimate of the DDREF for cancer risk.
Knowledge of adaptive responses, genomic instability, and bystander signaling between cells that may act to alter radiation cancer risk was judged to be insufficient to be incorporated in a meaningful way into the modeling of epidemiologic data. The same judgment is made with respect to the possible contribution to cancer risk of postirradiation genomic instability and bystander signaling between cells.
Genetic variation in the population is a potentially important factor in the estimation of radiation cancer risk. Strongly expressing cancer-predisposing mutations are judged from modeling studies to be too rare to distort population-based estimates of risk appreciably, but they are a significant issue in some medical radiation settings. The position regarding potentially more common variant genes that express only weakly remains uncertain.
Estimation of the heritable effects of radiation takes advantage of new information on human genetic disease and on mechanisms of radiation-induced germline mutation. The application of a new approach to genetic risk estimation leads the committee to conclude that low-dose induced genetic risks are very small compared to baseline risks in the population.
The committee judges that the balance of evidence from epidemiologic, animal, and mechanistic studies tends to favor a simple proportionate relationship at low doses between radiation dose and cancer risk. Uncertainties in this judgment are recognized and noted.
MODELS FOR ESTIMATING THE LIFETIME RISK OF CANCER
As in past risk assessments, the LSS cohort of survivors of the atomic bombings of Hiroshima and Nagasaki plays a principal role in developing the committee’s recommended cancer risk estimates. In contrast to previous BEIR reports, data on both cancer mortality and cancer incidence (from the Hiroshima and Nagasaki tumor registries) were available to the committee. The cancer incidence data analyzed by the committee included nearly 13,000 cases occurring in the period 1958–1998. In addition, the committee evaluated data on approximately 10,000 cancer deaths occurring in the period 1950–2000, in contrast to fewer than 6000 cancer deaths available to the BEIR V committee.
Although the committee did not conduct its own analyses of data from studies other than the LSS, for most studies with suitable data, results of analyses based on models similar to those used by the committee were available and were evaluated. For cancers of the breast and thyroid, several medically exposed groups offer quantitative data suitable for risk assessment, and the recommended models for these sites are those developed in published combined analyses of data from the relevant studies.
To use models developed primarily from the LSS cohort for the estimation of lifetime risks for the U.S. population, it was necessary to make several assumptions. Because of inherent limitations in epidemiologic data and in our understanding of radiation carcinogenesis, these assumptions involve uncertainty. Two important sources of uncertainty are (1) the possible reduction in risk for exposure at low doses and low-dose rates (i.e., the DDREF), and (2) the “transport” of risk estimates based on Japanese atomic bomb survivors to use in estimating risks for the U.S. population. With regard to the DDREF, the committee concluded that linear risk estimates obtained from the LSS cohort should be reduced by a factor of 1.1 to 2.3 for estimating risks at low doses and low dose rates, and the BEIR VII committee used a value of 1.5 to estimate solid cancer risks. To estimate the risk of leukemia, the BEIR VII model is linear-quadratic, since this model fitted the data substantially better than the linear model. The use of data on Japanese A-bomb survivors to estimate risks for the U.S. population (transport) is problematic for sites where baseline risks differ greatly between the two countries. For cancer sites other than breast and thyroid (where data on Caucasian subjects are available), the committee presents estimates based on the assumption that the excess risk due to radiation is proportional to baseline risks (relative risk transport) and also presents estimates based on the assumption the excess risk is independent of baseline risks. As a central estimate, the committee recommends a weighted estimate of these two results, with the ratio of the two used to reflect the uncertainty in transporting risks. For most sites, a weight of 0.7 is used for relative transport and a weight of 0.3 is used for absolute transport; the weighting is reversed for lung cancer.
The committee provides estimates of lifetime risks of both cancer incidence and mortality for leukemia, all solid cancers, and cancers of several specific sites: stomach, colon, liver, lung, female breast, prostate, uterus, ovary, bladder, and all other solid cancers. The committee’s models provide the basis for sex-specific estimates for exposure scenarios including single exposures at various ages, chronic exposure throughout life, or occupational exposure from age 18 to 65. These models are based primarily on the LSS study, with additional use of medical data for breast and thyroid.
As an example, Table 13-1 shows the estimated number of incident cancer cases and deaths expected to result if a population of 100,000 persons with an age distribution simi-