absolute risk (EAR)2 per 104 person-year (PY) per sievert are comparable, this suggests that absolute risk may be appropriate. However, other differences in the populations often confound such comparisons. Most of the relevant exposures occured for medical reasons, were generally protracted, and often were at higher doses than those received by atomic bomb survivors, making it difficult to interpret comparisons. Additional difficulties are dosimetry uncertainties and statistical variation, which is quite large in some studies. Furthermore, although many studies report estimates of the ERR per gray (ERR/Gy), few report estimates of the EAR per gray. Comparisons of estimates from the LSS and medical studies are also discussed in the material below on breast cancer and at the end of Chapter 12 after the BEIR VII risk estimates have been presented.
A second approach based on epidemiologic data is to investigate interactions of various risk factors with radiation. However, there are few studies with available data on both radiation and other risk factors and with sufficient power to distinguish multiplicative and additive interactions. Relevant data are reviewed below. A detailed discussion of interactions is given by UNSCEAR (2000b, Appendix H).
In the sections that follow, the committee first discusses the type of interaction that would be expected based on consideration of whether radiation and other risk factors act primarily as initiators or promoters. Because the correct transport model is not necessarily the same for all cancer sites, this is followed by a discussion of cancers of each of several specific sites. The etiology of each site-specific cancer is discussed briefly, including the role of various risk factors. A discussion of epidemiologic studies that address interactions of radiation and other risk factors then follows.
Although baseline risks for all solid cancers (as a single category) do not differ greatly between the United States and Japan, this occurs because of the canceling out of site-specific cancers that are higher in the United States (including breast, colon, lung, and prostate) and site-specific cancers that are higher in Japan (including stomach and liver). If the correct transport models differ by site, estimates of all solid cancers based on relative and absolute risk transport may not fully reflect the transport uncertainty.
Animal studies (Chapter 3) suggest that low-LET radiation acts principally as an initiator of tumorigenesis and is at best a weak tumor promoter. In addition, for many tumor types, relative risks (ratio of radiation-associated and spontaneous risks) are more comparable across animal strains than are absolute risks (Storer and others 1988). Thus, quantitative animal tumorigenesis data are most consistent with a relative risk transport model, although there are exceptions.
Current knowledge implies the following: (1) at low doses, radiation acts principally as an initiator of cancer (Chapter 3), and (2) many of the known cancer risk factors such as hormonal or reproductive factors, particularly for breast cancer risk, and chronic inflammation associated with microbial infection, for stomach and liver cancers (discussed in this chapter), tend to act at later stages in multistage tumorigenesis. In these latter cases, cancer risk modification is believed to be associated largely with the postinitiation clonal expansion of preneoplastic or malignant cells (Chapter 3). Genetic factors acting throughout cancer development may also modify risk (Chapter 3).
Biologically based risk projection models provide a simplistic, but useful, intuitive framework to evaluate the possible role of radiation in populations with different distributions of risk factors for specific cancer types. An example of such modeling approaches is given in Annex 10A, which summarizes judgments that can be made on the transport of cancer risk using the Moolgavkar and Knudson two stage clonal expansion model, viewing low-LET radiation as a tumor initiator. In simple terms, the model predicts that in the case of a radiogenic tumor type with a strong influence of promoters, one would favor a relative risk transportation model, whereas in the case of a tumor type with a strong influence of initiators, one would favor an absolute risk transportation model.
As briefly illustrated in Annex 10A, knowledge of the mechanistic factors that underlie tumor etiology can provide an important input to judgments on the most appropriate methodology for transportation of radiation cancer risk between different populations. This section provides an overview of the etiology of a selection of radiogenic human tumors.
Stomach cancer is a disease with a much higher background incidence in Japan than in the United States (IARC 2002). Risk factors for gastric cancer include the presence of conditions such as chronic atrophic gastritis, gastric ulcer, atrophic gastritis, and autoimmune gastritis associated with pernicious anemia. These cause an excessive rate of cell proliferation in the gastric epithelium and are therefore likely to act as promoters, increasing the chance of fixation of replication errors induced by radiation and dietary carcinogens (IARC 2003). Helicobacter pylori infection of the