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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2
FIGURE 4-4 Comparison of the relationship between heritability of liability and mutation component for the tenth postradiation generation with that at the new equilibrium, under the same conditions as those specified for Figure 4-2. The shaded areas of h2 (range: 0.3–0.8) are those of interest in the context of chronic diseases. Note that in this range, the MC at generation 10 is very small, whereas at the new equilibrium, it is equal to 1.
the original value for all subsequent generations). As expected, the first-generation MC is the same (i.e., very small) as that shown in Figure 4-3, and this is followed by a gradual decline back to zero in subsequent generations (data not shown).
Effects of Gene Interactions (Epistasis) and Sporadics
The effects of gene-gene interactions on quantitative phenotypes at risk of complex diseases are varied and do not lend themselves readily to modeling. However, when some assumptions about these interactions were incorporated in the FLTM, it was found that the results (at the new equilibrium as well as for the early postradiation generations) were basically the same as those under conditions of no interactions (data not shown but discussed in Denniston and others 1998; ICRP 1999).
In all of the model predictions discussed thus far, the possibility that some individuals may be affected by the disease for reasons unrelated to their genotypes (sporadic cases) was not considered. When these were taken into account, as expected the magnitude of MC was lower, both at the new equilibrium and in the early generations. The factor by which the numerical estimates of MC will change can be estimated to be [1 − (a/PT)], where (a/PT) represents the proportion of sporadic cases among the total number of affected individuals (a = number of sporadic cases; PT = total number of cases).
The most important conclusion from computer simulation studies is that when the population is exposed to small doses of radiation in every generation, the MC for chronic diseases is very small, being of the order of 1 to 2% in the first several postradiation generations including the first. Since one of the assumptions of the model is the simultaneous increase in mutation rate of all of the genes underlying a given chronic disease, which is unlikely to occur at low radiation doses, the effective MC in the early generations is likely to be much less than 1–2%. One would therefore predict that the expected increases in the frequency of chronic diseases (relative to the baseline frequency) will be even smaller in the first few postradiation generations.