Health Risks from Exposure to Low Levels of Ionizing Radiation BEIR VII Phase 2 (2006) / Chapter Skim
Currently Skimming:
10 Integration of Biology and Epidemiology
10 Integration of Biology and Epidemiology
Pages 239-258
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 239... ...
. Therefore, cellular responses to DNA damage and health effects; the an initial conclusion would be that the multistage process of possible implications of the knowledge of cancer mecha cancer development after ionizing radiation is unlikely to be nisms for projections of cancer risk over time and the trans substantially different from that which applies generally (i.e., port of that risk between populations; the shape of the that the DNA-damaging capacity of radiation is a crucial dose-response relationship for cancer risk at low doses; dose element in cancer risk)
|
From page 240... ...
diation will depend on whether radiation and the factor of Although multiplicative risk projection is clearly better interest act principally as initiators of cancer or act at later supported than additive risk projection, current epidemio- stages in multistage cancer development as discussed below. logic data indicate that relative risks may decrease with in- Two approaches based on epidemiologic data can inform creasing attained age or time since exposure, especially for us regarding the most appropriate transport method.
|
From page 241... ...
In these latter cases, cancer risk modirial below on breast cancer and at the end of Chapter 12 af- fication is believed to be associated largely with the ter the BEIR VII risk estimates have been presented. postinitiation clonal expansion of preneoplastic or malig A second approach based on epidemiologic data is to in- nant cells (Chapter 3)
|
From page 242... ...
evaluated the joint effect of Aflatoxins induce mutations in several genes involved in smoking and radiation exposure on lung cancer risks in Ahepatocellular carcinoma and are thus likely to be involved bomb survivors and found that they were significantly in the early or initiating stages of carcinogenesis. Hepatitis submultiplicative and consistent with an additive model.
|
From page 243... ...
Also, in a pooled alter either the expression or the function of these genes analysis of breast cancer mortality in Canadian fluoroscopy could therefore influence gene-environment interactions patients and A-bomb survivors, neither the ERRs nor the and enhance the increased breast cancer risk in women fol- EARs were found to differ significantly between the cohorts lowing radiation exposure (see Chapter 3)
|
From page 244... ...
The uncertainty involved in this States (standardized to the world population) , based on choice is reflected in the subjective confidence intervals that SEER registry data, was 10.8 and 6.7 per 100,000, respec- are provided as discussed in Chapter 12.
|
From page 245... ...
to the differences in baseline risks in Japan and the United The following data and conclusions are given in ChapStates, this finding supports the use of absolute risk trans- ters 1, 2, and 3 and are most pertinent to radiation risks in port. Furthermore, lung cancer analyses of A-bomb survivor the dose range 0100 mSv where epidemiologic and animal data based on EAR models may provide a more reliable data are inadequate.
|
From page 246... ...
In summary, the committee judges vincing argument for the inclusion of DDREF in judgments that the balance of scientific evidence at low doses tends to about cancer risk at low doses and low dose rates. The aniweigh in favor of a simple proportionate relationship be- mal data showing reduction in carcinogenic effectiveness, tween radiation dose and cancer risk.
|
From page 247... ...
The line analogous to the "high-dose linear apinduction by acute-dose low-LET radiation in which risks proximation" of Figure 10-1 is the one that results from linare observed only at two doses: zero and some particular ear model estimation with the LSS data. If a certain degree "high dose." If the true dose-response relationship is con- of curvature is presumed, then it is possible to define an LSS cave up to that dose, as the radiobiological data tend to sug- DDREF that correctly adjusts LSS linear risk in order to gest, then a line connecting the excess risk at high dose to the estimate cancer risk at low doses.
|
From page 248... ...
Plotted points are the estimated ERRs for solid cancer incidence (averaged over sex, for individuals exposed at age 30 at attained age 60) from LSS subjects in each of 11 dose categories.
|
From page 249... ...
If the radiobiologi2.0 3.0 5.0 7.0 3.1 cal estimate of 1.5 seems low, the committee believes that it is due not to a new interpretation of radiobiological curva aFor incidence of solid cancers and based on doses between 0 and 1.5 Sv, ture but rather to the use of an LSS DDREF that is specific to as in Figure 10-2. bDDREF = 1 + × high dose.
|
From page 250... ...
1.5 (1.1, 2.3) Given these unresolved issues, it is comforting that the estimate of LSS DDREF is consistent with the best-fitting NOTE: The 95% intervals are confidence intervals (likelihood ratio)
|
From page 251... ...
The data reviewed in Chapters 1 and 3 provide coherent evidence from cellular, animal, and clinical or epidemiologic studies that inheritance of certain germline gene mutations Induced Genomic Instability can predispose to radiation-induced cancer. The qualitative Induced genomic instability is a term used to describe a linkage between such epidemiologic or clinical and experiset of cellular phenomena whereby radiation exposure alters mental data are particularly strong for rare, strongly expressthe state of a cell in a way that generally leads to a persistent ing human mutations.
|
From page 252... ...
As mentioned earlier, the results of the extensive genetic epidemiologic studies of A-bomb survivors in Japan have shown no adverse effects in the progeny that could be attrib- SUMMARY uted to the radiation exposures (of the order of 0.4 Sv) sus The principal objective of this chapter is to highlight the tained by most survivors.
|
From page 253... ...
The AR per sievert could therefore be transported from · The committee judges that the balance of evidence from one population to another. epidemiologic, animal, and mechanistic studies tends to favor a simple proportionate relationship at low doses between radiation dose and cancer risk.
|
From page 254... ...
the results in risk due to the sum of K acute exposures of equal dose, D / K, Tables 1 and 2 because those risk estimates were not adadministered at separate times, is the sum of the individual justed for competing causes of death; (2) results for doses relative risks, and if an LQ dose-response model describes greater than 2 Gy; and (3)
|
From page 255... ...
This is a scaled profile curvature, it is necessary to understand the connection belikelihood function for from a model in which the risk tween age-specific failure rate and survival time. The human estimates of Figure 10B-2 are normally distributed with vari- risk models estimated with the LSS data are for age-specific ances that are proportional to the reciprocal of the squared failure rates, also known as hazard functions.
|
From page 256... ...
bution with mean and variance equal to the sample mean and The estimates depend highly on the dose range considered. sample variance of the three curvatures in the table.
|
From page 257... ...
The posterior density in the plished here could possibly lead to a better summarization of radiobiological information about curvature than provided in Figure 10B-4. Even a more thorough study, however, TABLE 10B-1 Estimates of Linear and Quadratic would similarly be obstructed by the subjectivity involved in Coefficients from Chromosome Aberration Induction the choice of dose range upon which LQ models are fit, by Studies and the Implicit Curvatures the inconsistency of animal experiment results, and by the difficulty in translating mouse results to human cancer rates.
|
From page 258... ...
258 BEIR VII FIGURE 10B-4 A summary of radiobiological evidence for curvature: the (profile) likelihood for curvature from the risk estimate data in Figure 10B-2, the (profile)
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.