Cancers, radiation-induced

Cancer is the major latent harmful effect produced by ionizing radiation and the one that most people exposed to radiation are concerned about. The ability of alpha, beta, and gamma radiation to produce cancer in virtually every tissue and organ in laboratory animals has been well-demonstrated. The development of cancer is not an immediate effect. In humans, radiation-induced leukemia has the shortest latent period at 2 years, while other radiation induced cancers have latent periods >20 years. The mechanism by which cancer is induced in living cells is complex and is a topic of intense study. Exposure to ionizing radiation can produce cancer at any site within the body however, some sites appear to be more common than others, such as the breast, lung, stomach, and thyroid. 

Radiation is one of the most important known environmental stimuli of cancer development. This environmental factor becomes especially dangerous for humans living in the areas affected by irradiation from nuclear accidents. Earlier we found that the administration of a mixture of vitamin E and a-lipoic acid to children living in the area of Chernobyl nuclear accident significantly and synergistically suppressed leukocyte oxygen radical overproduction [211]. Thus a-lipoic acid and a-lipoic acid + vitamin E supplements may be of interest as antioxidant preventive agents for the treatment of radiation-induced cancer development. 

Radiation is carcinogenic. The frequency of death from cancer of the thyroid, breast, lung, esophagus, stomach, and bladder was higher in Japanese survivors of the atomic bomb than in nonexposed individuals, and carcinogenesis seems to be the primary latent effect of ionizing radiation. The minimal latent period of most cancers was <15 years and depended on an individual s age at exposure and site of cancer. The relation of radiation-induced cancers to low doses and the shape of the dose-response curve (linear or nonlinear), the existence of a threshold, and the influence of dose rate and exposure period have to be determined (Hobbs and McClellan 1986). 

Radiation-induced cancers in humans are found to occur in the hemopoietic system, the lung, the thyroid, the liver, the bone, the skin, and other tissues. 

Some imcertainty characterizes the relationship between dose and latent period for radiation-induced cancer in man, for the data are few and somewhat at odds with experimental findings. Animal experiments generally show a shortening of latent period with increasing dose (UNSCEAR, 1977 Ma3meord, 1978). Human data are seldom reported but the experience of the A-bomb survivors lends itself to the investigation of this issue, and a recent report (Land and Tbkunaga, 1984) provides substantial evidence that the latency of solid tumors may be independent of dose. 

Whatever mathematical model is assumed for the dose-incidence relationship, it is noteworthy that susceptibility can vary markedly with age, so that the radiation-induced cancer excess at various times after irradiation may more nearly approximate a constant percentage of the natural age-specific incidence than a constant number of additional cases, depending on the neoplasm in question. For some individual neoplasms, but not the leukemias, the data do in fact suggest that the "relative risk model is more appropriate than the absolute risk model (see Section 6.1.7). For all neoplasms combined, also, the excess of radiation-induced cases at different times after irradiation approximates more nearly a constant percentage of the age-specific incidence. 

Baum, J.W. (1973). Population heterogeneity hypothesis on radiation induced cancer, Health Phys. 25,197. 

Maldague, P. (1969). Comparative study of experimentally induced cancer of the kidney in mice and rats with x-rays, page 439 in Radiation-Induced Cancer, IAEA STI/PUB/228 (International Atomic Energy Agency, Vienna). 

Finkel MP, Biskis BO, Jinkins PB. 1969b. Toxicity of radium-226 in mice. In Ericson A, ed. Radiation induced cancer. Vienna, Austria International Atomic Energy Agency, 369-391. 

Although rarely presented in a dose-response assessment, in nearly all cases the lower bound on the incremental probability of a response will be zero or less (see Figure 3.7). That is, the statistical model that accounts for the uncertainty in the results of an animal study also accommodates the possibility that no response may occur at low doses and that, in fact, there may be fewer responses (e.g., cancers) than observed in the control population at some low doses. The possibility of reduced responses at low doses also is shown by the lower confidence limit of data on radiation-induced cancers in some organs of humans including, for example, the pancreas, prostate, and kidney (Thompson et al., 1994). 

Radiation-induced cancer incidence also could be estimated using calculations of the probability of cancer incidence per unit activity intake of specific radionuclides by particular ingestion and inhalation pathways or the probability per unit activity concentration of specific radionuclides in the environment by particular pathways of external exposure (Eckerman etal., 1999) probabilities of fatal cancers for the different exposure pathways also have been calculated. These probability coefficients differ from those developed by ICRP (see Section 3.2.2.3.2) in that they are calculated with respect to activity of specific radionuclides rather than dose, and they thus bypass the need to estimate the effective dose. For external exposure, the methods used by Eckerman etal. (1999) and ICRP (1991) to estimate responses essentially are equivalent. However, there are significant differences in the methods used to estimate responses from intakes of radionuclides, and the results obtained by Eckerman et al. (1999) differ substantially in a few cases (e.g., intakes of 232Th)... 

However, this option presents some difficulties for radionuclides, because studies of radiation effects in human populations have focused on cancer fatalities as the measure of response and probability coefficients for radiation-induced cancer incidence have not yet been developed by ICRP or NCRP for use in radiation protection. Probabilities of cancer incidence in the Japanese atomic-bomb survivors have been obtained in recent studies (see Section 3.2.3.2), but probability coefficients for cancer incidence appropriate for use in radiation protection would need to take into account available data on cancer incidence rates from all causes in human populations of concern, which may not be as reliable as data on cancer fatalities. Thus, in effect, if incidence were used as the measure of stochastic response for radionuclides, the most technically defensible database on radiation effects in human populations available at the present time (the data on fatalities in the Japanese atomic-bomb survivors) would be given less weight in classifying waste. 

However, given the current state of knowledge and methods of dose-response assessment for substances that cause stochastic responses, there appear to be important technical and institutional impediments to the use of either incidence or fatalities exclusively. Data on radiation-induced cancer incidence and chemical-induced cancer fatalities for use at the low doses and dose rates relevant to health protection are not readily available, and current regulatory guidance calls for calculation of cancer incidence for hazardous chemicals. Since use of a common measure of response for all substances that cause stochastic responses may not be practical in the near term, both measures (fatalities for radionuclides and incidence for hazardous chemicals) could be used in the interest of expediency. The primary advantage of this approach is that the measures of stochastic response for radionuclides and hazardous chemicals would be based on the best available information from studies in humans and animals, and it would involve the fewest subjective modifying factors. This approach also would be the easiest to implement. 

The exposure scenario described in the previous example of domestic uranium mill tailings was used to classify the high-radium residues. The risk and dose assessments indicated a probability of radiation-induced cancer incidence of about 0.6, potential doses in excess of 10 Sv, and a risk index between 50 and 100. Thus, these residues would be classified as high-hazard waste, even under conditions of perpetual institutional control over near-surface disposal sites, and they would require some form of greater confinement disposal well below the ground surface. This conclusion is consistent with recommendations for disposition of these residues (NAS/ NRC, 1995b). 

For both humans and laboratory animals, one cannot currently distinguish between a radiation-induced cancer and a spontaneously occurring cancer (i.e., from an unknown cause). Therefore, statistical methods are used to determine whether radiation exposure is associated with an increase in cancer in a given study population. There have been several epidemiological studies in which definite dose-response relationships have been established for radiation-induced cancers. The best studied populations include atomic bomb survivors, Tinea capitis irradiation patients, ankylosing spondylitis irradiation patients, radium dial painters, radium therapy radium-224 patients, Thorotrast patients, uranium miners, Chernobyl fallout victims, and Mayak plutonium facility workers. 

Excess radiation-induced cancers have also been demonstrated in well-controlled studies using laboratory animals (e.g., mice, rats, and dogs). The data from animal studies are being used to supplement the dose-response information obtained from epidemiological studies in humans and are providing model systems for the investigations of the mechanisms of radiation-induced diseases such as cancer. 

Little, M. P., Heidenreich, W. F., Moolgavkar, S. H., Schollnberger, H., and Thomas, D. C. (2008). Systems biological and mechanistic modelling of radiation-induced cancer. Radiat Environ Biophys 47, 39-47. 

Much of this regulatory zeal was driven by the Delaney Clause, which amended the Food, Drug and Cosmetic Act of 1938. This clause forbids the addition of any amount of animal carcinogen to the food supply. This was originally based on our belief at the time that even one molecule of a carcinogen could cause cancer in humans. This concept was largely influenced by theories of radiation-induced cancer. Thresholds were not allowed. As we discussed, this is no longer considered valid since the processes of absorption, distribution, elimination, metabolism and cellular defense, and repair mechanisms make this possibility far less than remote. However, the United States... 

Radiation-induced cancer is due to a nonlethal mutation of somatic cells. The latent period between irradiation and the development of cancer varies from 4 to 40 years, the average being 7 to 12 years. Even relatively low doses of X-rays increased the risk of cancer. Of school children epilated with 300 to 400 r of unfil-tered 100-kV radiation, 1.6 percent had skin, thyroid, or parotid tumors 20 years later, while untreated control group showed only 0.2 percent such tumors. Apparently the mutated cells can survive 10 to 20 years before proliferating. ... 

The incidence of stochastic effects can only be treated in a probabilistic manner. Consider cancer first. In the United States the normal incidence of cancer (not necessarily fatal) in the adult population is 25 percent. The estimate for radiation-induced cancer is (1.5-4.5) x 10 per manSv [(I.5-4.5) x lO " per manrem]. To understand this estimate better, consider an example. In a group of 10,000 adult Americans, about 2500 cases of cancer will be detected (not necessarily fatal). If this group of 10,000 persons receives 0.01 Sv (1 rem) of radiation collectively, the estimated number of cancers due to this radiation dose is 1.5-4.5. Therefore, the total number of cancers expected to be detected will be between 2501.5 and 2504.5. The incidence of fatal cancer in the United States is 16.4 percent. The risk of deadly cancer from radiation is estimated to be (0.7-2.26) X 10 per manSv [(0.7-2.26) X lO " per manrem]. 

It is important to bear in mind that the number of radiation induced cancers in this cohort (a group of persons with a common statistical characteristic) is relatively small and thus the statistical uncertainty is large in 1950-1985 a total of 5,936 cases of cancer were reported compared to the statistically expected 5,596 in an imirradiated reference group of similar sex-age composition, i.e. an excess of only 6% (350 cases). 

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