& "Radiation Risk", 2003, special issue
2. PREDICTION OF RADIATION-INDUCED THYROID CANCERS AMONG RESIDENTS OF THE ORYOL OBLAST BASED ON THE ICRP MODELS 2.1. Model of radiation risks for thyroid cancer
Let us first define the terminology used here before describing the model for the radiation risk. A risk of disease (death) is understood as a probability m of developing disease by an individual during a given time interval. The risk or probability of developing disease depends on age, sex, profession, lifestyle, place of residence, time and other factors. By way of an example, let us consider a group of N persons not exposed to radiation, followed up for a year with a view to determine how many cases occurred in this group. If during a year E of persons (expected number of cases) developed a disease in this group, then the risk over a year will be estimated as m = E/N (the risk m is called spontaneous or background). Given N = 100 thousand people, then m is to the spontaneous incidence rate per 100 thousand persons. If the group was exposed to radiation, then the number of cases will change and be equal to O (observed number of cases). In absolute terms, the effect of exposure is characterized by the excess absolute risk EAR=O-E. The relative significance of exposure is described by EER excess relative risk. ERR = EAR/E = (O-E) /E. (sometimes called the probability of causation POC or simply PC ) defined as: (2.1) One of the key characteristics of the level of radiation-induced diseases is the attributive risk ATR
ATR =
ERR 1 + ERR
.
(2.2)
The attributive risk is the ratio of radiation-induced diseases to the number of all diseases. The attributive risk is often expressed in percent. The excess absolute risk EAR is calculated as:
EAR = m ERR ,
where m is the background incidence rate.
(2.3)
In this work the model of excess absolute risk BEIR-V [1] recommended by the ICRP is used for calculating thyroid cancer:
EAR = 2.5 10 4 D F S G ,
(2.4)
where F is the efficiency factor (for isotopes 125I, 131I F = 1/3, for other iodine isotopes F = 1); the sex factor S = 2/3 for males and S = 4/3 for females; the age factor G = 1 at g 18 and G = 0.5 at g > 18. The latent period is taken to be TL = 5 years. The calculation of radiation-induced risks requires a knowledge of the background incidence rates. We use the average Russian incidence rates for 1996 [2] given in Table 2.1 for the background rates. For comparison the table contains general cancer incidence rates. As can be seen, thyroid cancer is a fairly rare disease. Thyroid cancer makes, on average, only a few percent of all cancers. This section describes a model of radiation risks of thyroid cancer. This disease occurs 2-3 times more frequently in females than in males. In the subsequent chapter there is a projection of radiation risks of this disease for residents of the Oryol oblast.
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Table 2.1. Background incidence and death rates in 1996.
Incidence rate per 100 thousand persons All Cancer Thyroid Caner males females males females 12 11 0.00 0.00 11 8 0.04 0.09 10 8 0.13 0.40 16 14 0.25 0.91 20 24 0.30 2.0 23 37 0.59 2.8 36 67 0.74 4.5 64 114 0.89 5.9 136 194 1.2 8.7 289 314 2.3 11.6 543 421 3.4 13.0 804 480 2.8 10.8 1175 632 3.6 10.7 1539 755 3.8 10.1 1974 944 5.4 9.5 1814 856 3.6 7.1 Death rate per 1 thousand from all causes males females 4.45 3.33 0.61 0.37 0.58 0.33 2.14 0.80 4.12 0.98 4.96 1.22 6.57 1.57 8.56 2.24 12.0 3.32 16.8 5.09 23.3 7.46 30.5 10.5 41.3 15.9 55.6 24.5 71.0 39.0 138.0 106.
Age interval 0- 4 5- 9 10 - 14 15 - 19 20 - 24 25 - 29 30 - 34 35 - 39 40 - 44 45 - 49 50 - 54 55 - 59 60 - 64 65 - 69 70 - 74 >74
2.2. Demographic data and doses for the population of the Oryol oblast
The depositions from the Chernobyl accident resulted in radioactive contamination of the territories of the Bryansk, Kaluga, Lipetsk, Oryol, Ryazan and Tula oblasts. Starting from the moment of contamination the population of these territories was exposed to internal and external irradiation from a mix of a variety of fission products and activation products. The main exposure source were radioisotopes of iodine, cesium, strontium and plutonium. So far, mean thyroid doses have been calculated for residents of the indicated oblasts. Table 2.2 includes data on accumulated doses and populations of the rayons of the Oryol oblast. As of 1986 the general population of the oblast was 887 thousand people (of them 190 thousand children and 697 thousand adults). Table 2.2. Populations of rayons of the Oryol oblast and the accumulated doses averaged over each rayon.
Population Administrative name
BOLKHOVSKY VERKHOVSKY GLAZUNOVSKY DMITROVSKY DOLZHANSKY ZALEGOSHENSKY ZNAMENSKY KOLPNYANSKY KORSAKOVSKY KRASNOZORENSKY KROMSKY LIVENSKY MALOARKHANGELSKY MTSENSKY NOVODEREVENKOVSKY NOVOSILSKY ORLOVSKY POKROVSKY SVERDLOVSKY SOSKOVSKY TROSNYANSKY URITSKY KHOTYNETSKY SHABLYKINSKY TOTAL OBLAST
children 5339 5479 3728 4262 3480 4156 1438 5014 1129 2101 5524 18031 3476 14778 3276 2661 82741 4443 4317 2027 3140 4219 2896 2426 190095
adults 19586 20103 13677 15636 12768 15248 5277 18395 4143 7707 20266 66153 12755 54219 12021 9764 303552 16303 15841 7437 11521 15481 10627 8903 697393
total 24925 25582 17405 19898 16248 19404 6715 23409 5272 9808 25790 84184 16231 68997 15297 12425 386293 20746 20158 9464 14661 19700 13523 11329 887488
Accumulated thyroid dose (adults), mGy 17.1 8.59 14.3 21 5.29 9.03 8.97 7.73 10.5 12.4 14.8 5.8 22 8.05 9.08 10.5 9 10.3 14.4 12.8 15.9 10.8 6.73 10.5 13
Accumulated thyroid dose (children), mGy 71.4 28.4 49.5 84.3 16.3 31 27.3 24.6 36.7 35.4 54.6 21 66.1 32.2 29.4 36.7 40.6 31.3 48 37 48.9 38.3 21.6 34 38.7
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As a result of the intense rainfall on 28-29 April 1986 the territory of the Oryol oblast was contaminated by radioactivity. The rayons worst affected were Bolkhovsky, Dmitrovsky, Kromsky and Maloarkhangelsky rayons. The accumulated doses in children of these rayons exceed 50 mGy and the doses in adults are up to 22 mGy. Figures 1.15 and 1.16 of chapter 1 present the maps of the Oryol oblast with mean accumulated doses (iodine) in mGy in children and adults of the studied rayons, respectively. In adults the accumulated thyroid doses are about 3-4 times lower than those in children. As a consequence, the risk of radiation-induced thyroid cancers is estimated to be 6-8 times higher in children than in adults (for children the factor G=1 for adults G=0.5).
2.3. Mathematical model for predicting radiation-induced risks
In a general case, the dynamics of cancer incidence in the population with uniform doses is described by a system of differential equations with partial derivatives written as:
n n + = n ( mi + mi ) n + hi ( ni + ni ) + Q ( u , t ) t u ni ni + = mi n i ni hi ni t u ni ni + = mi n i ni hi ni t u
(2.5)
Here n is the number of healthy individuals, ni is the number of patients with the background i-th disease,
ni is the number of patients with radiation-induced i-th disease, is the background death rate, hi is the survival
rate for the i-th disease, i is the death rate from the i-th disease, Q accounts for birth rate and migration process. The background coefficients in equation (2.5) depend on time t and age u. The radiation-induced coefficients are a function of radiation dose and other parameters. If the number of diseases is k (1 I k), then the total number of equations equals to 2k + 1. Taking into account the dependence of the equation parameters on sex, the number of equations is doubled. If the dose is not uniform over the population, for each dose interval a system of equations similar to system (2.5) is written. At the initial time moment the distribution of population by age n(u,o) is specified. Assuming the maximum age um, n(u,t)=0 at u > um (further in calculations um = 90 years). Considering the uncertainty in the demographic and epidemiological data over the years since the accident and in projections, the prognostic model was based on the following assumptions. It is assumed that the accumulated radiation dose (iodine) was received only by the population living in the Oryol oblast in 1986. Thus, at a starting time moment the distribution n(u,s,0) of the population of each rayon by age u and sex s are considered to be known. As n(u,s,0) we take the age distribution of the population of the whole Oryol oblast normalized to the number of residents in a particular rayon. The changes in population as a result of background deaths from all causes at t>0 (with allowance for sex) is described by the equation:
n ( u , s , t ) n ( u , s , t ) + = ( u , s ) n( u , s , t ) , t u
the calculations the mean Russian death rates for 1996 shown in Table 2.1 are used.
(2.6)
where (u,s) is the death factor dependent only on age and sex. For brevity the sex parameter s is omitted. In To elucidate the influence of uncertainties in demographic data on prediction results we used standardized age distribution of population derived from the solution of the following equation:
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dn( u ) = ( u ) n( u ) du
(2.7)
at the initial condition n(0)=n0. This distribution (for each sex) was normalized to the number of residents of a given rayon. Figure 2.1 presents both age distributions of the population for the whole Oryol oblast.
Fig. 2.1. Age distribution of the population of the Oryol oblast. The solid line is the standardized distribution calculated with equation (2.7). The incidence rate for the i-th background disease (number of cases per year) for a given age at the time moment t>TL was calculated as follows:
ni ( u , t ) = mi ( u ) n( u , t ) ,
(2.8)
where mi(u) is the coefficient of the i-th incidence rate. The incidence rates are shown in Table 2.1. The incidence rate ni of radiation-induced diseases at a given age at the time moment t was calculated by the equation:
ni ( u , t ) = EARi ( u , g , t , D ) n( u , t ) .
found as follows:
(2.9)
The cumulative number of background Ni and radiation-induced Ni diseases at the time moment t>TL is
t um
Ni ( t ) = d ni ( u , )du ,
TL
(2.10)
Ni ( t ) = d ni ( u , )du .
TL
t
um
(2.11)
Corresponding lifetime risks are determined as Ni(um) and Ni(um) (i.e. the number of cases over the whole time of the cohort existence). Equation (2.6) was solved by the numerical method with the step of time and age integration of 1 year. Accordingly, the number of background and radiation-induced cases were calculated for each year.
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2.4. Information and reference software PUBRASS-2002
For calculating and predicting background and radiation-induced cancers in the residents of the Oryol oblast an information and reference software program PUBRASS-2002 (Public Risk ASSessment) has been developed. The size of this software is 1.8 Mb (execution module) and 0.5 Mb are the service files. The software is based on a mathematical model for predicting cancer risks described in the previous section. The software is written in the algorithmic language FORTRAN-90, the environment is Fortran Power Station 4.0. Figure 2.2 shows a part of the main window of the PUBRASS software with the main menu of 4 items (RISKS, CALCULATION RESULTS, INPUT DATA AND REFERENCES).
Fig. 2.2. Fragment of the display window of software PUBRASS-2002 with the main menu. Each item of the main menu contains a pull-down menu, as shown in Fig. 2.3. When the first item of the menu is activated, a dialogue window shows up and a user can select a rayon of the Oryol oblast or the whole oblast, type of cancer, age distribution, sex and age interval at the time of exposure. Among other things, a button REFERENCES is available in the dialogue window for obtaining explanatory information. The dialogue window is shown in Fig. 2.4.
Fig. 2.3. Fragment of the main window of software PUBRASS-2002 with pull-down menus.
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Fig. 2.4. Dialogue window for input of source data for calculating risks for residents of the Oryol oblast. Results of the calculation and the prediction of cancer risks are presented as time functions of risks and maps of the Oryol oblast with indication of cumulative risks (lifetime and current year values). Figure 2.5 presents a fragment of the screen display with the results of predicted incidence (number of persons) plotted. The is plot accompanied by brief information about the time dependence of risk. The second item of the menu RESULTS OF CALCULATION provides an opportunity to look at risks of interest. Activating the submenu MAPPED RISKS the user can select a map with risks of interest (background and radiation-induced). This window is shown in Fig. 2.6.
Fig. 2.5. Part of screen with the plot of predicted cases.
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The third item of the main menu INPUT DATA makes it possible to look at demographic and epidemiological data used in calculations. Demographic data and information about accumulated doses (cesium and iodine) are also presented as maps. The forth item of the main menu REFERENCES provides an opportunity to read a detailed description of software, its developer etc. It also contains a list of opened windows. Moreover, displayed information can be copied to the exchange buffer. For doing this, after activation of the item HIGHLIGHT GRAPHICS a part of the screen (plot of map) should be highlighted with a cursor. After copying the buffer content can be transferred to another document or graphic editor (the figure copied to the buffer has the format bmp).
Fig. 2.6. Dialogue window to select risk maps for residents of the Oryol oblast. The software PUBRASS can be used for calculating individual risks. Suppose a background and radiationinduced risk need to be determined for a person who received a dose at the age of 30 years. In this case the ageat-exposure interval of 30-30 should be specified.
2.5. Prediction of radiation-induced thyroid cancers in the population of the Oryol oblast
The section presents results of the calculations and prediction of background and radiation-induced thyroid cancers among residents of the Oryol oblast. All calculations were made using the software PUBRASS. We would like to stress again that all risks were calculated for people living in 1986 in the Oryol oblast. Those born after 1986 are not included in the projections. It was assumed that accumulated doses were received on the very same year. This must be true for the short-lived iodine. Calculations were made separately for children (0-14 years old in 1986) and adults (15 years of age and older in 1986). The changes in the whole exposed population over time are shown in Fig. 2.7 by a solid curve, and the dash line shows the number of exposed people who were under age 15 in 1986. The general population declines with time almost linearly, while the number of people in the age group less than 15 years of age starts decreasing significantly only 30 years after the accident.
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Fig. 2.7. Changes in the exposed population of the Oryol oblast over time. The broken line - population under age 15 in 1986. As was mentioned, thyroid cancer is a rare disease. The mean Russian incidence rate in 1996 is 3-4 cases a year per 100 thousand people. For children this rate is less than 0.5 cases each year are 100,000 children. In the Oryol oblast the same year the crude incidence rate was 14 cases a year per 100 thousand people.
2.5.1. Incidence in children
Figure 2.8 shows the changes with time of background (spontaneous) thyroid cancers in the population of the Oryol oblast in those less than 15 years of age (children) in 1986.
Fig. 2.8. Time changes in the number of background (spontaneous) thyroid cancers in the population of the Oryol oblast among those less than 15 years of age (children) in 1986.
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As can be seen from the figure, some 3 cases of background diseases are predicted to occur in the current year in this age group (this group includes people from 16 to 30 years old in the current year 2002). Since the group consists of children, for whom the background incidence is low, the number of cases in the first 10-15 years is low. Then the group ages and the incidence increases over time. Finally, the size of the group decreases rapidly as a result of mortality and the number of cases decreases accordingly. Figure 2.9 shows the time dependence of the cumulative (accumulated from 1992) number of thyroid cancer cases among persons who were under 15 years of age in 1986. It can be seen that the total number of thyroid cancer cases over the whole time of the existence of this group will be 500 cases. In the same figure the cumulative number of radiation-induced thyroid cancers is shown by the broken line. The lifetime number of radiation-induced cancers in this group is predicted to be 37 cases. Accordingly, the lifetime attributive risk will be about 7%.
Fig. 2.9. The same as in Fig. 2.8, but for cumulative number of cases starting from 1992 (excluding the latent period of 5 years). The broken line shows the cumulative number of radiation-induced thyroid cancers. The attributive risk accounts for the ratio of the number of radiation-induced cancers to the entire number of cases as percentage and is independent of parameters such as background incidence rate and size of studied population group. The time dependence of the attributive risk for residents of the Oryol oblast (children) is presented in Fig. 2.10. In the first years after the latent period, as follows from the figure, high values of attributive risk above 40% are observed. This value suggests that about half of all cases are radiation induced. In 2002 the attributive risk is about 18% (of 5 cases one is radiation induced). Starting from 2015 the attributive risk varies between 3% and 6%. Figures 2.11 and 2.12 show maps of the cumulative numbers of background and radiation-induced thyroid cancers among residents of the Oryol oblast as of 2002. In the Dmitrovsky rayon which was the worst contaminated (accumulated dose 84 mGy), according to estimates, as of 2002 there will be 0.3 background cases and 0.3 radiation-induced cases. In the most heavily populated Oryol rayon (dose of 40.6 mGy) the number of background cases is 5.8 and the number of calculated radiation-induced cases is 2.8.
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Fig. 2.10. The time change of the attributive risk of thyroid cancer for residents of the Oryol oblast under age 15 in 1986 (children).
Fig. 2.11. Map of cumulative background (spontaneous) thyroid cancer cases in the rayons of the Oryol oblast as of 2002 (children).
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Fig. 2.12. Map of cumulative radiation-induced thyroid cancers among children in the rayons of the Oryol oblast as of 2002. The cumulative attributive risks of thyroid cancer as of 2002 in persons under age 15 in 1986 appear to be quite high. On the average, in the Oryol oblast the attributive risk is about 30%. Thus, between 1992 and 2002 one out of every three cases is radiation-induced. Figure 2.13 presents a map with the values of cumulative attributive risk of thyroid cancer in the population of the Oryol oblast. For the Dmitrovsky rayon the attributive risk is as high as 50%, which means that of 5 out of 10 cases are radiation induced. The lowest attributive risk of thyroid cancer of 16% occurs in the residents of the Dolzhansky rayon (the accumulated dose is 16 mGy).
Fig. 2.13. Map of the cumulative attributive risk of thyroid cancer for the child populations of different rayons of the Oryol oblast as of 2002.
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2.5.2. Incidence of adults
As follows from the model, the radiation risk of thyroid cancer for adults ex...