els for site-specific cancers make use of data on all solid cancers to estimate the modifying effects of age at exposure and attained age, but make use only of data for the site of interest to estimate the overall level of risk.
Considerations in deciding on the sites for which individual estimates should be provided are whether or not the cancer has been linked clearly with radiation exposure and the adequacy of the data for developing reliable risk estimates. On the first point, it can be argued that the range of uncertainty for risk of a particular cancer is of interest regardless of whether or not a statistically significant dose-response had been observed, a position taken by NIH (2003). Cancers of the salivary glands, stomach, colon, liver, lung, breast, bladder, ovary, and thyroid and nonmelanoma skin cancer have all been linked clearly with radiation exposure in A-bomb survivor data, with evidence somewhat more equivocal for a few additional sites such as esophagus, gall bladder, and kidney. Other studies support many of these associations, and bone cancer has been linked with exposure to α-irradiation from 224Ra. Leukemia has been strongly linked with radiation exposure in several studies including those of atomic bomb survivors.
Another consideration in selecting sites for evaluation is the likelihood of exposure scenarios that will irradiate the site selectively. Here it is noted that inhalation exposures will selectively irradiate the lung, exposures from ingestion will selectively irradiate the digestive organs, exposure to strontium selectively irradiates the bone marrow, and exposure to uranium selectively irradiates the kidney.
Based on these considerations, the committee has provided models and mortality and incidence estimates for cancers of the stomach, colon, liver, lung, female breast, prostate, uterus, ovary, bladder, and all other solid cancers. Incidence estimates are also provided for thyroid cancer.
The inclusion of cancers of the prostate and uterus merits comment because these cancers are not usually thought to be radiation-induced and have not been evaluated separately in previous risk assessments. However, the committee did not want to include these cancers in the residual category of “all other solid cancers,” particularly since prostate cancer is much more common in the United States than in Japan.
This section describes the results of analyses of data on cancer incidence and mortality in the LSS cohort that were conducted by the committee with the help of RERF personnel acting as agents of the National Academies. Analyses of cancer incidence were based on cases diagnosed in the period 1958–1998. Analyses of cancer 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 excess relative risk models and excess absolute risk (EAR)2 models were evaluated. Methods were generally similar to those that have been 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). Additional detail is given in Annex 12B.
All analyses were based on the 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 (Gy) + 10 × neutron absorbed dose (Gy). The DS02 system provides estimates of doses to several organs of the body. For site-specific estimates, 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 cancer or all solid cancers excluding thyroid and nonmelanoma skin cancer. Additional discussion of the doses used in the analyses is given in Annex 12B.
Risk estimates for all solid cancers were obtained by summing the estimates for cancers of specific sites. However, the general form of the model and the estimates of the parameters that quantify the modifying effects of age at exposure and attained age were (with some exceptions) based on analyses of data on all solid cancers. Such analyses offer the advantage of larger numbers of cancer cases and deaths, which increases statistical precision.
As discussed in Chapter 6, most recent analyses of data on the LSS cohort have been based on either ERR models, in which the excess risk is expressed relative to the background risk, or EAR models, in which the excess risk is expressed as the difference in the total risk and the background risk. With linear dose-response functions, the general models for the ERR and EAR are given below:
where λ(c, s, a, b) denotes the background rate at zero dose, and depends on city (c), sex (s), attained age (a), and birth cohort (b). The terms βs ERR(e, a) and βs EAR(e, a) are, respectively, the ERR and the EAR per unit of dose expressed in sieverts, which may depend on sex (s), age at exposure (e), and attained age (a).