this population include its large size (slightly less than half of the survivors were alive in 2000); the inclusion of both sexes and all ages; a wide range of doses that have been estimated for individual subjects; and high-quality mortality and cancer incidence data. In addition, the whole-body exposure received by this cohort offers the opportunity to assess risks for cancers of a large number of specific sites and to evaluate the comparability of site-specific risks. Special studies of subgroups of the LSS have provided clinical data, biological measurements, and information on potential confounders or modifiers.
Mortality data for the period 1950–1997 have been evaluated in detail. Importantly, cancer incidence data from both the Hiroshima and the Nagasaki tumor registries became available for the first time in the 1990s. These data not only include nonfatal cancers, but also offer diagnostic information that is of higher quality than that based on death certificates, which is especially important when evaluating site-specific cancers. The more extensive data on solid cancer that are now available have allowed more detailed evaluation of several issues pertinent to radiation risk assessment. Analyses evaluating the shape of the dose-response and focusing on the large number of survivors with relatively low doses (less than 0.5 Sv) generally confirm the appropriateness of linear functions to describe solid cancer risks. Both excess relative risk and excess absolute risk models have been used to evaluate the modifying effects of sex, age at exposure, and attained age.
Health end points other than cancer have been linked with radiation exposure in the LSS cohort. Of particular note, a dose-response relationship to mortality from nonneoplastic disease has been demonstrated with statistically significant associations for the categories of heart disease; stroke; and diseases of the digestive, respiratory, and hematopoietic systems. However, noncancer risks at the low doses of interest for this report are especially uncertain, and the committee has not modeled the dose-response for nonneoplastic diseases, or developed risk estimates for these diseases.
Published studies on the health effects of medical exposures were reviewed to identify those that provide information for quantitative risk estimation. Particular attention was focused on estimating risks of leukemia and of lung, breast, thyroid, and stomach cancer in relation to radiation dose for comparison with the estimates derived from other exposed populations, in particular atomic bomb survivors.
For lung cancer, the excess relative risk (ERR)2 per gray from the studies of acute or fractionated high dose-rate exposures are statistically compatible and in the range 0.1–0.4 per Gy. For breast cancer, both the ERR and the excess absolute risk (EAR) appear to be quite variable across studies. A pooled analysis of A-bomb survivors and selected medically exposed cohorts indicated that the EAR for breast cancer was similar (about 10 per 104 person-years ([PY]) per gray at age 50) following acute and fractionated moderate to high-dose-rate exposure despite differences in baseline risks and dose rate. Women treated for benign breast conditions appeared to be at higher risk, whereas the risk was lower following protracted low-dose-rate exposures in hemangioma cohorts.
For thyroid cancer, all of the studies providing quantitative information about risks are studies of children who received radiotherapy for benign conditions. For subjects exposed below the age of 15, a linear dose-response was seen, with a leveling or decrease in risk at the higher doses used for cancer therapy (10+ Gy). An ERR of 7.7 per gray and an EAR of 4.4 per 104 PY per gray were derived from pooled analyses of data from medical exposures and atomic bomb survivors. Both estimates were significantly affected by age at exposure, with a strong decrease in risk with increasing age at exposure and little apparent risk for exposures after age 20. The ERR appeared to decline over time about 30 years after exposure but was still elevated at 40 years. Little information on thyroid cancer risk in relation to medical iodine-131 (131I) exposure in childhood was available. Studies of the effects of 131I exposure later in life provide little evidence of an increased risk of thyroid cancer.
For leukemia, ERR estimates from studies with average doses ranging from 0.1 to 2 Gy are relatively close, in the range 1.9 to 5 per gray, and are statistically compatible. Estimates of EAR are also similar across studies, ranging from 1 to 2.6 per 104 PY per gray. Little information is available on the effects of age at exposure or of exposure protraction.
For stomach cancer, the estimates of ERR per gray range from negative to 1.3. The confidence intervals are wide however, and they all overlap, indicating that these estimates are statistically compatible. Finally, studies of patients having undergone radiotherapy for Hodgkin’s disease or breast cancer suggest that there may be some risk of cardiovascular morbidity and mortality for very high doses and high-dose-rate exposures. The magnitude of the radiation risk and the shape of the dose-response curve for these outcomes are uncertain.
Numerous studies have considered the mortality and incidence of cancer among various occupationally exposed groups in the medical, manufacturing, nuclear, research, and aviation industries.
The most informative studies are those of nuclear industry workers (including the workers of Mayak in the former Soviet Union), for whom individual real-time estimates of